Is phantom pain experienced by amputees neurological?
Phantom pain
Sensations are recorded most frequently following the amputation of an arm or a leg, but may also occur following the removal of a breast, teeth, or an internal organ. Phantom limb pain is the feeling of pain in an absent limb or a portion of a limb. The pain sensation varies from individual to individual.
Somatosensory rehabilitation of pain
Sometimes, the hypoaesthetic territory is masked by a patch of skin which is painful to touch and is therefore not accessible. Since 1979, this stimulus induced pain is to be called allodynia in medicine. The original definition comes from Merksey and Bogduk (1994) “pain due to a stimulus which does not normally provoke pain”. In such situations, while doing the diagnostic testing of axonal lesions at the first occupational or physical therapy session, the two point discrimination test is impossible, because it induces pain.“This conflict between hypersensitivity and hypoaesthesia is commonly seen in the clinical setting in patients with CRPS”.
Palmitoylethanolamide
From a clinical perspective the most important and promising indications for PEA are linked to neuropathic and chronic pain states, such as diabetic neuropathic pain, sciatic pain, CRPS, pelvic pain and entrapment neuropathic painstates. In a blind pilot trial in 25 patients affected by temporomandibular joint's (TMJ) osteoarthritis or synovitis pain, patients were randomly to PEA or ibuprofen 600 mg three times a day for two weeks. Pain decrease after two weeks of treatment was significantly higher in PEA treated patients than in patients receiving the NSAID (p=0.0001) Masticatory function also improves more on PEA compared to the NSAID. In 2012, 20 patients suffering from thalidomide and bortezomib induced neuropathy were reported to have improved nerve functions and less pain after a two months treatment with PEA 600 mg daily. The authors pointed out that although a placebo effect might play a role in the reported pain relief, the changes in neurophysiological measures clearly indicated that PEA exerted a positive action on the myelinated fibre groups. 30 patients suffering from neuropathic pain, which were refractory to treatment with analgesics, included pregabalin, were responding well in 45 days, with a decrease of painscores > 50% when pregabalin was tapered in again, up to 600 mg/day in combination with PEA, without signs of drug-drug interaction. In 2013 a review was published on the clinical efficacy and safety of PEA in flu, based on a 6 double blind placebo controlled RCT's. This review underscores the anti-inflammatory action of PEA. These effects are also the explanation of PEA's retinoprotectant effects.
Pain in amphibians
The nerve impulses of the nociception response may be conducted to the brain thereby registering the location, intensity, quality and unpleasantness of the stimulus. This subjective component of pain involves conscious awareness of both the sensation and the unpleasantness (the aversive, negative affect). The brain processes underlying conscious awareness of the unpleasantness (suffering), are not well understood.
Bone pain
Stimulation of specialized pain-sensitive nerve fibers (nociceptors) that innervate bone tissue leads to the sensation of bone pain. Bone pain originates from both the periosteum and the bone marrow which relay nociceptive signals to the brain creating the sensation of pain. Bone tissue is innervated by both myelinated (A beta and A delta fiber) and unmyelinated (C fiber) sensory neurons. In combination, they can provide an initial burst of pain, initiated by the faster myelinated fibers, followed by a slower and longer-lasting dull pain initiated by unmyelinated fibers.
Pain asymbolia
Pain asymbolia, also called pain dissociation, is a condition in which pain is experienced without unpleasantness. This usually results from injury to the brain, lobotomy, cingulotomy or morphine analgesia. Preexisting lesions of the insula may abolish the aversive quality of painful stimuli while preserving the location and intensity aspects. Typically, patients report that they have pain but are not bothered by it; they recognize the sensation of pain but are mostly or completely immune to suffering from it.
Sensory neuron
Nociceptors respond to potentially damaging stimuli by sending signals to the spinal cord and brain. This process, called nociception, usually causes the perception of pain. They are found in internal organs as well as on the surface of the body. Nociceptors detect different kinds of damaging stimuli or actual damage. Those that only respond when tissues are damaged are known as "sleeping" or "silent" nociceptors.
Mirror box
Based on the observation that phantom limb patients were much more likely to report paralyzed and painful phantoms if the actual limb had been paralyzed prior to amputation (for example, due to a brachial plexus avulsion), Ramachandran and Rogers-Ramachandran proposed the "learned paralysis" hypothesis of painful phantom limbs Their hypothesis was that every time the patient attempted to move the paralyzed limb, they received sensory feedback (through vision and proprioception) that the limb did not move. This feedback stamped itself into the brain circuitry through a process of Hebbian learning, so that, even when the limb was no longer present, the brain had learned that the limb (and subsequent phantom) was paralyzed.
Nerve
A pinched nerve occurs when pressure is placed on a nerve, usually from swelling due to an injury, or pregnancy and can result in pain, weakness, numbness or paralysis, an example being carpal tunnel syndrome. Symptoms can be felt in areas far from the actual site of damage, a phenomenon called referred pain. Referred pain can happen when the damage causes altered signalling to other areas.
Karen Davis (neuroscientist)
Davis has also worked on variety of chronic pain conditions, concussion, and phantom pain. She has demonstrated that findings support the hypothesis that the thalamic representation of the amputated limb remains functional in amputees with phantoms Through several studies, she has shown important interactions between pain and cognition, by studying how brain networks shift their function towards pain while multitasking on cognitive tasks (Seminowicz et al., 2007; Erpelding et al., 2013) or when processing multimodal sensory information (Downar et al., 2000) or during mind wandering (Kucyi et al., 2013). She has introduced two influential theories that builds on the neuromatrix concept of Melzack. In the "pain switch" concept (Davis et al., 2015), she emphasizes the basic feeling of "ouch" that must be represented by a core brain mechanism, regardless of pain intensity or quality. The other concept is called the Dynamic Pain Connectome which emphasizes that spatiotemporal representation of pain in the brain is dynamic and includes activity in the salience and default mode network as well as the ascending nociceptive and antinociceptive pathways.
Pain empathy
Synesthesia occurs when sensory information in one cognitive pathway causes a sensation through another cognitive pathway. One form of synesthesia will cause a person to see certain colors when triggered by certain numbers, letters, or words. Pain synesthesia is a form of synesthesia that causes a person to experience pain when seeing pain empathetic eliciting stimuli. The most common group for reporting pain synesthesia are patients with phantom limb syndrome.
Phantom pain
Mirror box therapy allows for illusions of movement and touch in a phantom limb by inducing somatosensory and motor pathway coupling between the phantom and real limb. Many patients experience pain as a result of a clenched phantom limb, and because phantom limbs are not under voluntary control, unclenching becomes impossible. This theory proposes that the phantom limb feels paralyzed because there is no feedback from the phantom back to the brain to inform it otherwise. Vilayanur S. Ramachandran believes that if the brain received visual feedback that the limb had moved, then the phantom limb would become unparalyzed.
Tactile hallucination
Hallucinations of pain and touch are very rare in schizophrenic disorders but 20% of patients with schizophrenia experience some sort of tactile hallucinations along with visual and auditory hallucinations. The most common tactile hallucination in patients with schizophrenia is a sensation in which a patch of their skin is stretched elastically across their head. They vary in intensity, range and speed at which they feel this stretching painful sensation. They are usually triggered by emotional cues such as guilt, anger, fear and depression. Other types of tactile hallucinations takes on a sexual form in patients with schizophrenia. Patients with schizophrenia may sometimes experience the feeling of being kissed or the feeling of someone lying by their side in response to their emotion of being lonely. Additionally, they occasionally hallucinate the feeling of small animals such as snakes crawling over their body. Such vivid tactile sensation of an object that is not present results from the unsuccessful attempt of the brain trying to perceive objects that are novel and that represent unreal situations usually triggered by guilt and fear. Patients with schizophrenia also have a hard time portraying emotions as they divert most of their energy to control the pain from their tactile hallucinations.
Pain in fish
Sometimes a distinction is made between "physical pain" and "emotional" or "psychological pain". Emotional pain is the pain experienced in the absence of physical trauma, for example, the pain experienced by humans after the loss of a loved one, or the break-up of a relationship. It has been argued that only primates and humans can feel "emotional pain", because they are the only animals that have a neocortexa part of the brain's cortex considered to be the "thinking area". However, research has provided evidence that monkeys, dogs, cats and birds can show signs of emotional pain and display behaviours associated with depression during or after a painful experience, specifically, a lack of motivation, lethargy, anorexia, and unresponsiveness to other animals.
Compensatory hyperhidrosis
Phantom sweating is another form of autonomic neuropathy. It can be observed in patients with nerve damage (following accidents), diabetes mellitus and as a result of sympathectomy. Phantom sweating is a sensation that one is sweating, while the skin remains dry. Sufferers can not distinguish whether it is real sweating or just a sensation. The phenomena is experienced in the anhidriotic, denervated area of the body, presenting an abnormal sympathetic nervous system function.
Sensory neuron
Ever since scientists observed cortical remapping in the brain of Taub's Silver Spring monkeys, there has been a lot of research into sensory system plasticity. Huge strides have been made in treating disorders of the sensory system. Techniques such as constraint-induced movement therapy developed by Taub have helped patients with paralyzed limbs regain use of their limbs by forcing the sensory system to grow new neural pathways. Phantom limb syndrome is a sensory system disorder in which amputees perceive that their amputated limb still exists and they may still be experiencing pain in it. The mirror box developed by V.S. Ramachandran, has enabled patients with phantom limb syndrome to relieve the perception of paralyzed or painful phantom limbs. It is a simple device which uses a mirror in a box to create an illusion in which the sensory system perceives that it is seeing two hands instead of one, therefore allowing the sensory system to control the "phantom limb". By doing this, the sensory system can gradually get acclimated to the amputated limb, and thus alleviate this syndrome.
Phantom pain
Pharmacological techniques are often continued in conjunction with other treatment options. Doses of pain medications needed often drop substantially when combined with other techniques, but rarely are discontinued completely. Tricyclic antidepressants, such as amitriptyline, and sodium channel blockers, mainly carbamazepine, are often used to relieve chronic pain, and recently have been used in an attempt to reduce phantom pains. Pain relief may also be achieved through use of opioids, ketamine, calcitonin, and lidocaine.
Phantom limb
Despite a great deal of research on the underlying neural mechanisms of phantom limb pain there is still no clear consensus as to its cause. Peripheral mechanisms (areas of the nervous system outside the brain) and central neural mechanisms (inside the cortex) are among the hypotheses that have gained the most support over recent years. However, none of these theoretical constructs appears to be able to explain the phenomenon of phantom limb pain independently and many experts believe that multiple mechanisms are likely responsible.
Neuroplasticity
The relationship between phantom limb sensation and neuroplasticity is a complex one. In the early 1990s V.S. Ramachandran theorized that phantom limbs were the result of cortical remapping. However, in 1995 Herta Flor and her colleagues demonstrated that cortical remapping occurs only in patients who have phantom pain. Her research showed that phantom limb pain (rather than referred sensations) was the perceptual correlate of cortical reorganization. This phenomenon is sometimes referred to as maladaptive plasticity.
Small fiber peripheral neuropathy
Sensory symptoms of small fiber neuropathy are highly variable. Common complaints include paresthesias, dysesthesias, and insensitivity to pain. "Paresthesias" are abnormal sensations. They are often described as numbness, burning, cold, prickling, pins and needles along with other symptoms. "Dysesthesias" are unpleasant sensations, either spontaneous or evoked. A light breeze, the feeling of clothes, or even a soft touch can cause pain.
Insensitivity to pain can be particularly problematic. One may be bleeding or have a skin injury without even knowing it.
Phantosmia
Phantosmia (phantom smell), also called an olfactory hallucination or a phantom odor is smelling an odor that is not actually there. It can occur in one nostril or both. Unpleasant phantosmia, cacosmia, is more common and is often described as smelling something that is burned, foul, spoiled, or rotten. Experiencing occasional phantom smells is normal and usually goes away on its own in time. When hallucinations of this type do not seem to go away or when they keep coming back, it can be very upsetting and can disrupt an individual's quality of life.
Tactile hallucination
Phantom limb pain is a type of tactile hallucination because it creates a sensation of excruciating pain in a limb that has been amputated. In 1996, VS Ramachandran conducted a research on several amputees to pinpoint the neural reasons behind these illusionary pains. Most of these amputees that had an unbearable phantom limb pain are reported by patients whose limb was paralyzed before amputation. VS Ramachandran proposed the "learned paralysis" hypothesis. The hypothesis suggested that every time the patients tried to move their paralyzed limb, they received sensory feedback (through vision and proprioception) that the limb did not move. This feedback hardwired itself into the brain circuitry, so that, even when the limb was no longer present, the brain had learned that the phantom limb was paralyzed. As a treatment for phantom limb pains, VS Ramachandran devised a mirror box that would superimpose the mirror image of the normal arm in place of the missing arm and the patient would immediately be relieved of the pain. This suggested that the brain had a plastic nature in the somatosensory system and the brain had reorganized its somatosensory region to accommodate for this new change. Patients that experience this phantom limb pain are very important in research studies for their role in determining brain plasticity. The vivid tactile sensation of the arm that is no longer present suggest the highly complex nature of the brain to reorganize different functions which were once thought to be hardwired to specific regions (localization).
Neuralgia
Atypical trigeminal neuralgia (ATN) is a rare form of neuralgia and may also be the most misdiagnosed form. The symptoms can be mistaken for migraines, dental problems such as temporomandibular joint disorder, musculoskeletal issues, and hypochondriasis. ATN can have a wide range of symptoms and the pain can fluctuate in intensity from mild aching to a crushing or burning sensation, and also to the extreme pain experienced with the more common trigeminal neuralgia. ATN pain can be described as heavy, aching, and burning. Sufferers have a constant migraine-like headache and experience pain in all three trigeminal nerve branches. This includes aching teeth, ear aches, feeling of fullness in sinuses, cheek pain, pain in forehead and temples, jaw pain, pain around eyes, and occasional electric shock-like stabs. Unlike typical neuralgia, this form can also cause pain in the back of the scalp and neck. Pain tends to worsen with talking, facial expressions, chewing, and certain sensations such as a cool breeze. Vascular compression of the trigeminal nerve, infections of the teeth or sinuses, physical trauma, or past viral infections are possible causes of ATN.
Chronic wound pain
Depending on the sensation associated with neuropathic pain, it may be considered as acute or chronic. Acute neuropathic pain is associated with burning, squeezing, throbbing, shooting, or electric shock sensations that resolve. Neuropathic sensations such as numbness, tingling, and prickling are considered as chronic neuropathic pain. Chronic neuropathic pain may be intermittent or continuous, and may remain unresolved post tissue healing.
Phantom limb
A phantom limb is the sensation that an amputated or missing limb is still attached. Approximately 60 to 80% of individuals with an amputation experience phantom sensations in their amputated limb, and the majority of the sensations are painful. Phantom sensations may also occur after the removal of body parts other than the limbs, e.g. after amputation of the breast, extraction of a tooth (phantom tooth pain) or removal of an eye (phantom eye syndrome).
Pain
Paraplegia, the loss of sensation and voluntary motor control after serious spinal cord damage, may be accompanied by girdle pain at the level of the spinal cord damage, visceral pain evoked by a filling bladder or bowel, or, in five to ten per cent of paraplegics, phantom body pain in areas of complete sensory loss. This phantom body pain is initially described as burning or tingling, but may evolve into severe crushing or pinching pain, or the sensation of fire running down the legs or of a knife twisting in the flesh. Onset may be immediate or may not occur until years after the disabling injury. Surgical treatment rarely provides lasting relief.
Phantom limb
In 2012 an experiment was conducted in which it was demonstrated that the movement of phantom limbs are "real" movements that involve the execution of a motor command. Amputees can also carry out imaginary movements of their phantom limbs; however, these movements do not lead to a feeling that the phantom limb has changed position. This research indicates that clinicians using motor training for pain relief need to distinguish between imagined movements and real movements of phantom limbs.
Trigeminal neuralgia
TN needs to be distinguished from other forms of unilateral pain which are related to damage to the trigeminal nerve by trauma to the face or dental treatments. This is often termed painful trigeminal neuropathy or post-traumatic neuropathy as some sensory changes can be noted e.g. decrease in pain sensation or temperature. This is important as different care pathways are used. Trigeminal pain can also occur after an attack of herpes zoster, and post-herpetic neuralgia has the same manifestations as in other parts of the body. Trigeminal deafferentation pain (TDP), also termed anesthesia dolorosa, is from intentional damage to a trigeminal nerve following attempts to surgically fix a nerve problem. This pain is usually constant with a burning sensation and numbness. TDP is very difficult to treat as further surgeries are usually ineffective and possibly detrimental to the person.
Pain in amphibians
Pain is an aversive sensation and feeling associated with actual, or potential, tissue damage. It is widely accepted by a broad spectrum of scientists and philosophers that non-human animals can perceive pain, including pain in amphibians.
Pain
Neuropathic pain is caused by damage or disease affecting any part of the nervous system involved in bodily feelings (the somatosensory system). Neuropathic pain may be divided into peripheral, central, or mixed (peripheral and central) neuropathic pain. Peripheral neuropathic pain is often described as "burning", "tingling", "electrical", "stabbing", or "pins and needles". Bumping the "funny bone" elicits acute peripheral neuropathic pain.
Proprioception
People who have a limb amputated may still have a confused sense of that limb's existence on their body, known as phantom limb syndrome. Phantom sensations can occur as passive proprioceptive sensations of the limb's presence, or more active sensations such as perceived movement, pressure, pain, itching, or temperature. There are a variety of theories concerning the etiology of phantom limb sensations and experience. One is the concept of "proprioceptive memory", which argues that the brain retains a memory of specific limb positions and that after amputation there is a conflict between the visual system, which actually sees that the limb is missing, and the memory system which remembers the limb as a functioning part of the body. Phantom sensations and phantom pain may also occur after the removal of body parts other than the limbs, such as after amputation of the breast, extraction of a tooth (phantom tooth pain), or removal of an eye (phantom eye syndrome).
Psychological pain
Other descriptions of psychological pain are "a wide range of subjective experiences characterized as an awareness of negative changes in the self and in its functions accompanied by negative feelings", "a diffuse subjective experience ... differentiated from physical pain which is often localized and associated with noxious physical stimuli", and "a lasting, unsustainable, and unpleasant feeling resulting from negative appraisal of an inability or deficiency of the self."
Clinical neurochemistry
Nociception is the form of somatic sensation that detects potentially tissue-damaging noxious stimuli. Peripheral nociceptors uniquely express transient receptor potentials which are sensitive to potentially-damaging mechanical, chemical, or thermal stimuli. Nociceptors also contain receptors for pain and inflammatory-related mediators or cytokines. Peripheral nociceptors transmit noxious stimuli to the dorsal root ganglia, the dorsal horn, and further to the trigeminal ganglia in the brain. Pain has both a localizing somatic sensory component and an aversive emotional and motivational component. Pain travels through a variety of pathways via first pain on Alpha Delta fibers and second pain on slowly conducting C-fibers.
Extended physiological proprioception
People with amputations have reported phantom limbs. This serves as evidence that the brain is hard-wired to perceive body image, making it notable that sensory input and proprioceptive feedback are not essential in its formation. Losing an anatomical part through amputation sets a person up for complex perceptual, emotional, and psychological responses. Such responses include phantom limb pain, which is the painful feeling some amputees incur after amputation in the area lost. Phantom limb pain permits a natural acceptance and use of prosthetic limbs.
Hyperpathia
Hyperpathia is a clinical symptom of certain neurological disorders wherein nociceptive stimuli evoke exaggerated levels of pain. This should not be confused with allodynia, where normally non-painful stimuli evoke pain.
Phantom pain
Deep brain stimulation is a surgical technique used to alleviate patients from phantom limb pain. Prior to surgery, patients undergo functional brain imaging techniques such as PET scans and functional MRI to determine an appropriate trajectory of where pain is originating. Surgery is then carried out under local anesthetic, because patient feedback during the operation is needed. In the study conducted by Bittar et al., a radiofrequency electrode with four contact points was placed on the brain. Once the electrode was in place, the contact locations were altered slightly according to where the patient felt the greatest relief from pain. Once the location of maximal relief was determined, the electrode was implanted and secured to the skull. After the primary surgery, a secondary surgery under general anesthesia was conducted. A subcutaneous pulse generator was implanted into a pectoral pocket below the clavicle to stimulate the electrode. It was found that all three patients studied had gained satisfactory pain relief from the deep brain stimulation. Pain had not been completely eliminated, but the intensity had been reduced by over 50% and the burning component had completely vanished.
Phantom pain
Although the use of mirror therapy has been shown to be effective in some cases there is still no widely accepted theory of how it works. In a 2010 study of phantom limb pain, Martin Diers and his colleagues found that "In a randomized controlled trial that used graded motor imagery ... and mirror training, patients with complex regional pain syndrome or phantom limb pain showed a decrease in pain as well as an improvement in function post-treatment and at the 6-month follow-up. And it was shown that the order of treatment mattered." This study found that mirrored imagery produced no significant cortical activity in patients with phantom limb pain and concluded that "The optimal method to alter pain and brain representation, and the brain mechanisms underlying the effects [of] mirror training or motor imagery, are still unclear."
Optic neuropathy
Nutritional deficiencies affect the whole body, so pain or loss of sensation in the arms and legs (peripheral neuropathy) is often seen in patients with nutritional optic neuropathies. There was an epidemic of nutritional optic neuropathy among afflicted Allied prisoners of war of the Japanese during World War II. After four months of food deprivation, the prisoners of war developed vision loss in both eyes that appeared suddenly. They also had pain in their extremities and hearing loss. There is an endemic tropical neuropathy in Nigeria that may be due to a nutritional deficiency, but this has not been proven.
Phantom limb
Although not all phantom limbs are painful, people will sometimes feel as if they are gesturing, feel itches, twitch, or even try to pick things up. The missing limb often feels shorter and may feel as if it is in a distorted and painful position. Occasionally, the pain can be made worse by stress, anxiety and weather changes. Phantom limb pain is usually intermittent. The frequency and intensity of attacks usually declines with time.
Cortical remapping
Phantom limb pain is considered to be caused from functional cortical reorganization, sometimes called maladaptive plasticity, of the primary sensorimotor cortex. Adjustment of this cortical reorganization has the potential to help alleviate PLP. One study taught amputees over a two-week period to identify different patterns of electrical stimuli being applied to their stump to help reduce their PLP. It was found that the training reduced PLP in the patients and reversed the cortical reorganization that had previously occurred. 
However, a recent study by Tamar R. Makin suggests that instead of PLP being caused by maladaptive plasticity, it may actually be pain induced. The maladaptive plasticity hypothesis suggests that once afferent input is lost from an amputation, cortical areas bordering the same amputation area will begin to invade and take over the area, affecting the primary sensorimotor cortex, seeming to cause PLP. Makin now argues that chronic PLP may actually be 'triggered' by "bottom-up nociceptive inputs or top-down inputs from pain-related brain areas" and that the cortical maps of the amputation remain intact while the "inter-regional connectivity" is distorted.
Phantom pain
In addition to peripheral mechanisms, spinal mechanisms are thought to have an influencing role in phantom pains. Peripheral nerve injury can lead to the degeneration of C fibers in the dorsal horn of the spinal cord, and terminating A fibers may subsequently branch into the same lamina. If this occurs, A fiber inputs could be reported as noxious stimuli. Substance P, involved in the transmission of pain signals, is usually expressed by Aδ and C fibers, but following peripheral nerve damage, substance P is expressed by Aβ fibers. This leads to hyperexcitability of the spinal cord, which usually occurs only in the presence of noxious stimuli. Because patients with complete spinal cord injury have experienced phantom pains, there must be an underlying central mechanism responsible for the generation of phantom pains.
V. S. Ramachandran
When an arm or leg is amputated, patients often continue to feel vividly the presence of the missing limb as a "phantom limb" (an average of 80%). Building on earlier work by Ronald Melzack (McGill University) and Timothy Pons (NIMH), Ramachandran theorized that there was a link between the phenomenon of phantom limbs and neural plasticity in the adult human brain. In 1993, working with T.T. Yang who was conducting MEG research at the Scripps Research Institute, Ramachandran demonstrated that there had been measurable changes in the somatosensory cortex of a patient who had undergone an arm amputation. Ramachandran theorized that there was a relationship between the cortical reorganization evident in the MEG image and the referred sensations he had observed in other subjects. (In 1996 Knecht et al. published an analysis of Ramachandran's hypothesis that concluded that there was no topographic relationship between referred sensations and cortical reorganization in the primary cortical areas.) Neuroscientists continue to investigate the question of which neural processes are related to phantom limb phenomena.
Biofeedback
Flor (2002) trained amputees to detect the location and frequency of shocks delivered to their stumps, which resulted in an expansion of corresponding cortical regions and significant reduction of their phantom limb pain.
Phantom limb
Vilayanur S. Ramachandran hypothesized that phantom limb sensations in humans could be due to reorganization in the somatosensory cortex, which is located in the postcentral gyrus, and which receives input from the limbs and body. Ramachandran and colleagues illustrated this hypothesis by showing that stroking different parts of the face led to perceptions of being touched on different parts of the missing limb. Ramachandran argued that the perception of being touched in different parts of the phantom limb was the perceptual correlate of cortical reorganization in the brain. However, research published in 1995 by Flor et al. demonstrated that pain (rather than referred sensations) was the perceptual correlate of cortical reorganization. In 1996 Knecht et al. published an analysis of Ramachandran's hypothesis that concluded that there was no topographic relationship between referred sensations and cortical reorganization in the primary cortical areas. Recent research by Flor et al. suggests that non-painful referred sensations are correlated with a wide neural network outside the primary cortical areas.
Pain in amphibians
In 2002, James Rose, from the University of Wyoming, published reviews arguing that fish cannot feel pain because they lack a neocortex in the brain. If the presence of a large, considerably developed neocortex is required for experiencing pain, as Rose suggests, this theory would eliminate birds, amphibians, other non-mammalian animals, and even some mammals from having the capacity to experience pain. Other researchers do not believe that animal consciousness requires a neocortex, but can arise from homologous subcortical brain networks. Animal behaviouralist Temple Grandin argues that fish (and therefore, presumably, amphibians) could still have consciousness without a neocortex because "different species can use different brain structures and systems to handle the same functions."
Targeted reinnervation
With the left-arm amputation woman mentioned above, her phantom limb pain returned after surgery. Though at a lesser degree and resolved within 4 weeks, it still presented a serious risk because it is unclear whether it will resolve in other future patients.
Additionally, surgery was unsuccessful with a patient because severe nerve injuries were not detectable until during the surgery.
Ronald Melzack
After studying for his Ph.D. in 1954 with D. O. Hebb at McGill University in Montreal, he began to work with patients who suffered from "phantom limb" pain — people who feel pain in an arm or leg that has been removed. He found that pain often has little survival value, and some pains are entirely out of proportion to the degree of tissue damage, sometimes continuing long after injured tissues have healed. While still a postdoctoral student, Melzack began collecting "pain words" and putting them into classes that belonged together, like "hot," "burning," "scalding," and "searing".
Huda Akil
In 1970 Akil joined John Liebeskind, an assistant professor at UCLA who was interested in the neurobiology of pain, and more specifically focused on the neural circuitry of phantom pain, and the idea that phantom pain was not a purely physical phenomenon, but had a psychological role as well. Another member of the lab observed that electrical stimulation reduced, rather than enhanced pain experience, which inspired Akil and fellow graduate student, David Mayer, to continue to research this phenomenon, which they later referred to as “stimulation produced analgesia" (SPA). Working on rats, they found that stimulation at several mesencephalic and diencephalic sites eradicated responsiveness to painful stimuli and left other sensory modes relatively unaffected. This idea of SPA became the topic of Akil’s Ph.D. dissertation. Further research in this area was conducted in the rat by employing the D'Amour and Smith tail flick test in order to investigate role played by the cerebral monoamines, dopamine, noradrenaline, and serotonin. Akil and colleagues used four different approaches to alter transmission in monoamine pathways: depletion of monoamine stores, replacement of depleted monoamine stores, potentiation of monamine systems, and blockade of catecholamine receptors; the four approaches produced internally consistent results. In 1977, they discovered that the narcotic antagonist naloxone partially reverses analgesia produced by focal electrical stimulation of the brain. In this study analgesia was produced in the periaqueductal gray matter, which is an area of the brain that is known to contain a large number of opiate binding sites. This study along with results from other studies conducted at the time suggested that there is a natural neural system in the brain, which uses a morphine-like substance to produce analgesia, however it was not known if the activation of this system was brought about pharmacologically by direct receptor stimulation or electrically by release of the endogenous substance.
Neuroplasticity
In the phenomenon of phantom limb sensation, a person continues to feel pain or sensation within a part of their body that has been amputated. This is strangely common, occurring in 60–80% of amputees. An explanation for this is based on the concept of neuroplasticity, as the cortical maps of the removed limbs are believed to have become engaged with the area around them in the postcentral gyrus. This results in activity within the surrounding area of the cortex being misinterpreted by the area of the cortex formerly responsible for the amputated limb.
Phantom limb
Until recently, the dominant hypothesis for the cause of phantom limbs was irritation in the severed nerve endings (called "neuromas"). When a limb is amputated, many severed nerve endings are terminated at the residual limb. These nerve endings can become inflamed, and were thought to send anomalous signals to the brain. These signals, being functionally nonsense, were thought to be interpreted by the brain as pain. Treatments based on this hypothesis were generally failures. In extreme cases, surgeons would perform a second amputation, shortening the stump, with the hope of removing the inflamed nerve endings and causing temporary relief from the phantom pain. But instead, the patients' phantom pains increased, and many were left with the sensation of both the original phantom limb, as well as a new phantom stump, with a pain all its own. In some cases, surgeons even cut the sensory nerves leading into the spinal cord or in extreme cases, even removed the part of the thalamus that receives sensory signals from the body.
Referred pain
Referred pain, also called reflective pain, is pain perceived at a location other than the site of the painful stimulus. An example is the case of angina pectoris brought on by a myocardial infarction (heart attack), where pain is often felt in the neck, shoulders, and back rather than in the thorax (chest), the site of the injury. The International Association for the Study of Pain has not officially defined the term; hence several authors have defined it differently.
Amputation
A large proportion of amputees (50–80%) experience the phenomenon of phantom limbs; they feel body parts that are no longer there. These limbs can itch, ache, burn, feel tense, dry or wet, locked in or trapped or they can feel as if they are moving. Some scientists believe it has to do with a kind of neural map that the brain has of the body, which sends information to the rest of the brain about limbs regardless of their existence. Phantom sensations and phantom pain may also occur after the removal of body parts other than the limbs, e.g. after amputation of the breast, extraction of a tooth (phantom tooth pain) or removal of an eye (phantom eye syndrome).
Pain
Phantom pain is pain felt in a part of the body that has been amputated, or from which the brain no longer receives signals. It is a type of neuropathic pain.
Neuropathic pain
Neuropathic pain is pain caused by damage or disease affecting the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous and/or episodic (paroxysmal) components. The latter resemble stabbings or electric shocks. Common qualities include burning or coldness, "pins and needles" sensations, numbness and itching.
Mirror-touch synesthesia
Mirror touch responses are not limited to feeling touch. Mirror touch synesthetes have a higher ability to feel empathy than non-synesthetes, and can therefore feel the same emotions that someone else may be observed to feel. Additionally, some individuals experience pain when observing someone else in pain, and this is a condition usually developed from birth. Approximately 30% of the normal population experience some form of this condition and around 16% of amputees report synesthetic pain after an amputation. This condition can either be acquired or developed. In the congenital condition, synesthetes experience pain in the same location as the observed pain; however, in the acquired condition, high intensity pain is felt at the same location as the trauma.
Phantom pain
Under ordinary circumstances, the genetically determined circuitry in the brain remains largely stable throughout life. It was thought, until about 30 years ago, that no new neural circuits could be formed in the adult mammalian brain. Recently, functional MRI studies in amputees have shown that almost all patients have experienced motor cortical remapping. The majority of motor reorganization has occurred as a downward shift of the hand area of the cortex onto the area of face representation, especially the lips. Sometimes there is a side shift of the hand motor cortex to the ipsilateral cortex. In patients with phantom limb pain, the reorganization was great enough to cause a change in cortical lip representation into the hand areas only during lip movements. It has also been found that there is a high correlation between the magnitude of phantom limb pain and the extent to which the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortical reorganization has occurred. Additionally, as phantom pains in upper extremity amputees increased, there was a higher degree of medial shift of the facial motor representation. There are multiple theories that try to explain how cortical remapping occurs in amputees, but none have been supported to a great extent.
Atypical facial pain
Trigeminal neuralgia is another example of a cause of facial pain. Neuralgia refers to pain in the distribution of a nerve (or nerves), and commonly implies paroxysmal (sudden) pain, although the accepted IASP definition specifies that the term should not be restricted to mean paroxysmal pain. Classic trigeminal neuralgia refers to sudden, shooting pain in the face, which is usually short lived and brought on by accidental stimulation of trigger points on the face, as may occur when washing. Trigeminal neuralgia has been described as one of the most painful conditions possible. Trigeminal neuralgia and AFP are traditionally considered separate, since AFP typically involves constant, often burning pain and trigeminal neuralgia classically shows paroxysmal, shooting pain, but in reality there is some overlap in their features. In 2005 researchers proposed a new classification of trigeminal neuralgia which described a type of trigeminal neuralgia where the pain was constant and burning. They theorized that this type was a progression of untreated classic trigeminal neuralgia, and represented worsening neural injury. There were seven proposed sub-types of trigeminal neuralgia (TN) in this classification (see table), and the final category was reserved for facial pain caused by somatoform disorder. This last category (TN7) was termed atypical facial pain, although many cases that would otherwise be traditionally labelled as AFP would fall into other groups in this classification, especially into the second group. In a publication of the Trigeminal Neuralgia Association (TNA), the following was said about this new classification and AFP:
Sense
Nociception (physiological pain) signals nerve-damage or damage to tissue. The three types of pain receptors are cutaneous (skin), somatic (joints and bones), and visceral (body organs). It was previously believed that pain was simply the overloading of pressure receptors, but research in the first half of the 20th century indicated that pain is a distinct phenomenon that intertwines with all of the other senses, including touch. Pain was once considered an entirely subjective experience, but recent studies show that pain is registered in the anterior cingulate gyrus of the brain. The main function of pain is to attract our attention to dangers and motivate us to avoid them. For example, humans avoid touching a sharp needle, or hot object, or extending an arm beyond a safe limit because it is dangerous, and thus hurts. Without pain, people could do many dangerous things without being aware of the dangers.
Referred pain
Referred pain can be indicative of nerve damage. A case study done on a 63-year-old man with an injury sustained during his childhood developed referred pain symptoms after his face or back was touched. After even a light touch, there was a shooting pain in his arm. The study concluded that his pain was possibly due to a neural reorganization which sensitized regions of his face and back after the nerve damage occurred. It is mentioned that this case is very similar to what phantom limb syndrome patients suffer. This conclusion was based on experimental evidence gathered by V. Ramachandran in 1993, with the difference being that the arm that is in pain is still attached to the body.
Neuroplasticity
Individuals who suffer from chronic pain experience prolonged pain at sites that may have been previously injured, yet are otherwise currently healthy. This phenomenon is related to neuroplasticity due to a maladaptive reorganization of the nervous system, both peripherally and centrally. During the period of tissue damage, noxious stimuli and inflammation cause an elevation of nociceptive input from the periphery to the central nervous system. Prolonged nociception from the periphery then elicits a neuroplastic response at the cortical level to change its somatotopic organization for the painful site, inducing central sensitization. For instance, individuals experiencing complex regional pain syndrome demonstrate a diminished cortical somatotopic representation of the hand contralaterally as well as a decreased spacing between the hand and the mouth. Additionally, chronic pain has been reported to significantly reduce the volume of grey matter in the brain globally, and more specifically at the prefrontal cortex and right thalamus. However, following treatment, these abnormalities in cortical reorganization and grey matter volume are resolved, as well as their symptoms. Similar results have been reported for phantom limb pain, chronic low back pain and carpal tunnel syndrome.
Phantom pain
Neuromas formed from injured nerve endings at the stump site are able to fire abnormal action potentials, and were historically thought to be the main cause of phantom limb pain. Although neuromas are able to contribute to phantom pain, pain is not completely eliminated when peripheral nerves are treated with conduction blocking agents. Physical stimulation of neuromas can increase C fiber activity, thus increasing phantom pain, but pain still persists once the neuromas have ceased firing action potentials. The peripheral nervous system is thought to have at most a modulation effect on phantom limb pain.
Amyotrophic lateral sclerosis
Pain is a symptom experienced by most people with ALS and can take the form of neuropathic pain (pain caused by nerve damage), spasticity, muscle cramps, and nociceptive pain caused by reduced mobility and muscle weakness; examples of nociceptive pain in ALS include contractures (permanent shortening of a muscle or joint), neck pain, back pain, shoulder pain, and pressure ulcers.
Pain in amphibians
Amphibians, particularly anurans, fulfill several physiological and behavioural criteria proposed as indicating that non-human animals may experience pain. These fulfilled criteria include a suitable nervous system and sensory receptors, opioid receptors and reduced responses to noxious stimuli when given analgesics and local anaesthetics, physiological changes to noxious stimuli, displaying protective motor reactions, exhibiting avoidance learning and making trade-offs between noxious stimulus avoidance and other motivational requirements.
The Tale of the Dueling Neurosurgeons
Kean begins the chapter with the sad tale of George Dedlow. George Dedlow had fought in the Civil War and in turn had both his arms and both his legs amputated for various reasons. These amputations brought on another neurological phenomenon: phantom limbs. George Dedlow, amongst millions of other war amputees, felt pain in limbs that he did not have.
Mirror-touch synesthesia
It has been suggested that symptoms of mirror-touch synesthesia can occur in amputees. 98% of amputees report phantom sensations in their amputated limb, and one of the studied treatments for phantom limb pain has involved a mirror box. In this treatment, the amputee places their good arm into a mirror box, allowing the image of the arm to reflect where the amputated arm normally would be. When touch is applied to the good arm, amputees have reported corresponding sensations in their phantom limb. These cases can be considered mirror-touch synesthesia because a visual stimulus was able to elicit a tactile sensation. Studies have looked further into determining whether amputees actually experience mirror touch synesthesia. Four amputees were recruited in a study and asked to observe an assistant's arm being touched at various angles. 61 out of the 64 trials experienced mirror-touch sensations, and when the arm was wiggled, the sensations were enhanced. Finally, one amputee experienced a cold sensation when observing ice cubes touching the assistant's arm. Although there is evidence that mirror-touch synesthesia occurs in amputees, recent data has been inconclusive.
History of pain theory
Because of the only relatively recent discovery of neurons and how they conduct and interpret signals, including sensations such as pain, within the body, various theories have been proposed as to the causes of pain and its role or function. Even within seemingly limited groups, such as the ancient Greeks, there were competing theories as to the root cause of pain. Aristotle did not include a sense of pain when he enumerated the five senses; he, like Plato before him, saw pain and pleasure not as sensations but as emotions ("passions of the soul"). Alternatively, Hippocrates believed that pain was caused by an imbalance in the vital fluids of a human. At this time, neither Aristotle nor Hippocrates believed that the brain had any role to play in pain processing but rather implicated the heart as the central organ for the sensation of pain.
Phantosmia
Other olfactory disorders such as hyposmia and anosmia have been found to be a symptom of mood disorders (depression). However, it is not known what olfactory disorders occur and if they are indeed a symptom of a depressive disorder.
It has been proposed that phantosmia may be an early sign of the neurodegenerative disease Parkinson's disease. It may also be a sign of an intracranial hemorrhage (brain tumours or epilepsy).
Other studies have also found that the symptoms of phantosmia have been alleviated after the patient has been treated for depression.
Another case of a 70-year-old male reported that his first abnormal symptoms were irregular bowel movements. After this the patient developed irregular eye movements and had developed a sleep and behavior disorder after this he developed phantosmia; which was described to be as "stinky and unpleasant". The patient did not display the following symptoms: loss of awareness, confusion, automatisms, convulsive seizures or auditory/visual hallucinations.
Multiple sclerosis signs and symptoms
Pain can be severe and debilitating, and can have a profound effect on the quality of life and mental health of the sufferer. 
Certain types of pain are thought to sometimes appear after a lesion to the ascending or descending tracts that control the transmission of painful stimulus, such as the anterolateral system, but many other causes are also possible.
The most prevalent types of pain are thought to be headaches (43%), dysesthetic limb pain (26%), back pain (20%), painful spasms (15%), painful Lhermitte's phenomenon (16%) and Trigeminal Neuralgia (3%). These authors did not however find enough data to quantify the prevalence of painful optic neuritis.
Auriculotemporal nerve
Pain from parotitis, a condition that can be caused by mumps, will be carried by the auriculotemporal nerve to the brain.
Phantom limb
In 2013, experiments involving eight subjects were reported by Nadia Bolognini (University of Milano-Bicocca) in which transcranial direct current stimulation (tDCS) was used to temporarily reduce phantom limb pain. The researchers found that this type of stimulation could produce short-term (under 90 minutes) reduction of pain without affecting other amputation-related phenomena.
Atypical trigeminal neuralgia
As noted in material published by the [US] National Pain Foundation: "atypical facial pain is a confusing term and should never be used to describe patients with trigeminal neuralgia or trigeminal neuropathic pain. Strictly speaking, AFP is classified as a "somatiform pain disorder"; this is a psychological diagnosis that should be confirmed by a skilled pain psychologist. Patients with the diagnosis of AFP have no identifiable underlying physical cause for the pain. The pain is usually constant, described as aching or burning, and often affects both sides of the face (this is almost never the case in patients with trigeminal neuralgia). The pain frequently involves areas of the head, face, and neck that are outside the sensory territories that are supplied by the trigeminal nerve. It is important to correctly identify patients with AFP since the treatment for this is strictly medical. Surgical procedures are not indicated for atypical facial pain."
Hyperesthesia
Hyperesthesia (or hyperaesthesia) is a condition that involves an abnormal increase in sensitivity to stimuli of the sense. "When a non-noxious stimulus causes the sensation of pain the area will be termed hyperaesthetic". Stimuli of the senses can include sound that one hears, foods that one tastes, textures that one feels, and so forth. Increased touch sensitivity is referred to as "tactile hyperesthesia", and increased sound sensitivity is called "auditory hyperesthesia". Tactile hyperesthesia may be a common symptom of many neurologic disorders such as herpes zoster, peripheral neuropathy and radiculopathies. In 1979, and then in 1994, Merskey, Bogduk, Noordenbos, Devor and others (a subcommittee of International Association for the Study of Pain) proposed, instead of hyperaesthesia, the concept of allodynia, meaning "other pain", defined as a pain resulting from a stimulus that does not normally provoke pain.
Peripheral neuropathy
In the most common form, length-dependent peripheral neuropathy, pain and parasthesia appears symmetrically and generally at the terminals of the longest nerves, which are in the lower legs and feet. Sensory symptoms generally develop before motor symptoms such as weakness. Length-dependent peripheral neuropathy symptoms make a slow ascent of leg, while symptoms may never appear in the upper limbs; if they do, it will be around the time that leg symptoms reach the knee. When the nerves of the autonomic nervous system are affected, symptoms may include constipation, dry mouth, difficulty urinating, and dizziness when standing.
Tactile hallucination
Tactile hallucination is the false perception of tactile sensory input that creates a hallucinatory sensation of physical contact with an imaginary object. It is caused by the faulty integration of the tactile sensory neural signals generated in the spinal cord and the thalamus and sent to the primary somatosensory cortex (SI) and secondary somatosensory cortex (SII). Tactile hallucinations are recurrent symptoms of neurological diseases such as schizophrenia, Parkinson's disease, Ekbom's syndrome and delerium tremens. Patients who experience phantom limb pains also experience a type of tactile hallucination. Tactile hallucinations are also caused by drugs such as cocaine and alcohol.
Chemotherapy-induced peripheral neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and often irreversible condition featuring pain, numbness, tingling and sensitivity to cold in the hands and feet (sometimes progressing to the arms and legs) that afflicts between 30% and 40% of patients undergoing chemotherapy. Chemotherapy drugs associated with CIPN include thalidomide, the epothilones such as ixabepilone, the vinca alkaloids vincristine and vinblastine, the taxanes paclitaxel and docetaxel, the proteasome inhibitors such as bortezomib, and the platinum-based drugs cisplatin, oxaliplatin and carboplatin. Whether CIPN arises, and to what degree, is determined by the choice of drug, duration of use, the total amount received and whether the patient already has peripheral neuropathy. Though the symptoms are mainly sensory – pain, tingling, numbness and temperature sensitivity – in some cases motor nerves are affected, and occasionally, also, the autonomic nervous system.
Glutamate carboxypeptidase II
Researchers have been able to show that effective and selective GCPII inhibitors are able to decrease the brain's levels of glutamate and even provide protection from apoptosis or degradation of brain neurons in many animal models of stroke, amyotrophic lateral sclerosis, and neuropathic pain. This inhibition of these NAAG peptidases, sometimes referred to as NPs, are thought to provide this protection from apoptosis or degradation of brain neurons by elevating the concentrations of NAAG within the synapse of neurons. NAAG then reduces the release of glutamate while stimulating the release of some trophic factors from the glia cells in the central nervous system, resulting in the protection from apoptosis or degradation of brain neurons. It is important to note, however, that these NP inhibitors do not seem to have any effect on normal glutamate function. The NP inhibition is able to improve the naturally occurring regulation instead of activating or inhibiting receptors that would disrupt this process. Research has also shown that small-molecule-based NP inhibitors are beneficial in animal models that are relevant to neurodegenerative diseases. Some specific applications of this research include neuropathic and inflammatory pain, traumatic brain injury, ischemic stroke, schizophrenia, diabetic neuropathy, amyotrophic lateral sclerosis, as well as drug addiction. Previous research has found that drugs that are able to reduce glutamate transmission can relieve the neuropathic pain, although the resultant side-effects have limited a great deal of their clinical applications. Therefore, it appears that, since GCPII is exclusively recruited for the purpose of providing a glutamate source in hyperglutamatergic and excitotoxic conditions, this could be an alternative to avert these side-effects. More research findings have shown that the hydrolysis of NAAG is disrupted in schizophrenia, and they have shown that specific anatomical regions of the brain may even show discrete abnormalities in the GCP II synthesis, so NPs may also be therapeutic for patients suffering with schizophrenia. One major hurdle with using many of the potent GCPII inhibitors that have been prepared to date are typically highly polar compounds, which causes problems because they do not then penetrate the blood–brain barrier easily.
Saphenous nerve
The saphenous nerve can experience entrapment syndrome from exercises involving the quadriceps or from prolonged walking or standing. It is characterized by a burning sensation in most patients. Pain often occurs at night, long after the physical exercise which induced it has stopped, and may be aggravated by climbing stairs. Usually, in this case, motor function of the lower leg will not be impaired. This is a key distinction between saphenous nerve neuropathy and lower back radiculopathy. Saphenous nerve neuropathy only demonstrates "sensory alterations", while lumbar radiculopathy will affect the motor, sensory, and deep tendon reflexes of the lower leg.
Capnellene
Capnellene derivatives have recently been identified as possible treatments for neuropathic pain. Neuropathic pain is characterized by damage to peripheral or central nerves that results in pathological nociceptive transmission, the neuronal process that responds noxious stimuli. Two capnellene derivatives Δ-capnellene-8β,10α-diol and 8α-acetoxy-Δ-capnellene-10α-ol demonstrate potential as analgesics capable of attenuating neuropathic pain. These compounds have been shown "in vivo" to reduce two proteins that mediate inflammation, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). "In vivo", Δ-capnellene-8β,10α-diol inhibited hyperalgesia behavior in the mouse model for neuropathic pain in a dose-dependent manner. Additionally, treatment with Δ-capnellene-8β,10α-diol inhibited the up-regulation of immunoreactivity in the mouse model, specifically targeting the production of COX-2. Unlike many non-steroidal anti-inflammatory drugs(NSAIDs), Δ-capnellene-8β,10α-diol is advantageous in its selectivity for the COX isoenzyme COX-2, avoiding many of the gastrointestinal side effects associated with the inhibition of COX-1. This fact would allow for the administration of Δ-capnellene-8β,10α-diol in higher doses, potentially offering significant relief from neuropathic pain.
Postherpetic neuralgia
Postherpetic neuralgia (PHN) is neuropathic pain which occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus (herpes zoster, also known as shingles). Typically, the nerve pain (neuralgia) is confined to an area of skin innervated by a single sensory nerve, which is known as a dermatome. PHN is defined as dermatomal nerve pain that persists for more than 90 days after an outbreak of herpes zoster affecting the same dermatome. Several types of pain may occur with PHN including continuous burning pain, episodes of severe shooting or electric-like pain, and a heightened sensitivity to gentle touch which would not otherwise cause pain (mechanical allodynia) or to painful stimuli (hyperalgesia). Abnormal sensations and itching may also occur.
The nerve pain of PHN is thought to result from damage in a peripheral nerve which was affected by the reactivation of the varicella zoster virus. PHN typically begins when the herpes zoster vesicles have crusted over and begun to heal, but can begin in the absence of herpes zoster—a condition called "zoster sine herpete".
There is no treatment which modifies the disease course of PHN; therefore, controlling the affected person's symptoms is the main goal of treatment. Medications applied to the skin such as capsaicin or topical anesthetics (e.g., lidocaine) are used for mild pain and can be used in combination with oral medications for moderate to severe pain. Oral anticonvulsant medications such as gabapentin and pregabalin are also approved for treatment of PHN. Tricyclic antidepressants reduce PHN pain but their use is limited by side effects. Opioid medications are not generally recommended for treatment except in specific circumstances and under the care of a pain specialist due to mixed evidence of efficacy and concerns about potential for abuse and addiction.
PHN is the most common long-term complication of herpes zoster. The incidence and prevalence of PHN are uncertain due to varying definitions. Approximately 20% of people affected by herpes zoster report pain in the affected area three months after the initial episode of herpes zoster and 15% of people similarly report this pain two years after the herpes zoster rash. Since herpes zoster occurs due to reactivation of the varicella zoster virus, which is more likely to occur with a weakened immune system, both herpes zoster and PHN occur more often in the elderly and in people with diabetes mellitus. Risk factors for PHN include older age, a severe herpes-zoster rash, and pain during the herpes zoster episode. PHN is often very painful and can be quite debilitating. Affected individuals often experience a decrease in their quality of life.
Neuroproteomics
Traumatic brain injury is defined as a “direct physical impact or trauma to
the head followed by a dynamic series of injury and repair events”. Recently, neuroproteomics have been applied to studying the disability that over 5.4 million Americans live with. In addition to physically injuring the brain tissue, traumatic brain injury induces the release of glutamate that interacts with ionotropic glutamate receptors (iGluRs). These glutamate receptors acidify the surrounding intracranial fluid, causing further injury on the molecular level to nearby neurons. The death of the surrounding neurons is induced through normal apoptosis mechanisms, and it is this cycle that is being studied with neuroproteomics. Three different cysteine protease derivatives are involved in the apoptotic pathway induced by the acidic environment triggered by glutamate. These cysteine proteases include calpain, caspase, and cathepsin. These three proteins are examples of detectable signs of traumatic brain injury that are much more specific than temperature, oxygen level, or intracranial pressure.
Proteomics thus also offers a tracking mechanism by which researchers can monitor the progression of traumatic brain injury, or a chronic disease such as Alzheimer’s or Parkinson’s. Especially in Parkinson’s, in which neurotransmitters play a large role, recent proteomic research has involved the study of synaptotagmin. Synaptotagmin is involved in the calcium-induced budding of vesicle containing neurotransmitters from the presynaptic membrane. By studying the intracellular mechanisms involved in neural apoptosis after traumatic brain injury, researchers can create a map that genetic changes can follow later on.
Alternating hemiplegia
Alternating hemiplegia is a form of hemiplegia that has an ipsilateral and contralateral presentation in different parts of the body. The disorder is characterized by recurrent episodes of paralysis on one side of the body. There are multiple forms of alternating hemiplegia, Weber's syndrome, middle alternating hemiplegia, and inferior alternating hemiplegia. This type of syndrome can result from a unilateral lesion in the brainstem affecting both upper motor neurons and lower motor neurons. The muscles that would receive signals from these damaged upper motor neurons result in spastic paralysis. With a lesion in the brainstem, this affects the majority of limb and trunk muscles on the contralateral side due to the upper motor neurons decussation after the brainstem. The cranial nerves and cranial nerve nuclei are also located in the brainstem making them susceptible to damage from a brainstem lesion. Cranial nerves III (Oculomotor), VI (Abducens), and XII (Hypoglossal) are most often associated with this syndrome given their close proximity with the pyramidal tract, the location which upper motor neurons are in on their way to the spinal cord. Damages to these structures produce the ipsilateral presentation of paralysis or palsy due to the lack of cranial nerve decussation (aside from the trochlear nerve) before innervating their target muscles. The paralysis may be brief or it may last for several days, many times the episodes will resolve after sleep. Some common symptoms of alternating hemiplegia are mental impairment, gait and balance difficulties, excessive sweating and changes in body temperature.
Pain in amphibians
Several scientists and scientific groups have expressed the belief that amphibians can feel pain, however, this remains somewhat controversial due to differences in brain structure and the nervous system compared with other vertebrates.
Dysesthesia
Occlusal dysesthesia, or "phantom bite," is characterized by the feeling that the bite is "out of place" (occlusal dystopia) despite any apparent damage or instability to dental or oromaxillofacial structures or tissue. Phantom bite often presents in patients that have undergone otherwise routine dental procedures. Short of compassionate counseling, evidence for effective treatment regimes is lacking.Although dysesthesia is similar to phantom limb syndrome, they should not be confused. In phantom limb, the sensation is present in an amputated or absent limb, while dysesthesia refers to discomfort or pain in a tissue that has not been removed or amputated. The dysesthetic tissue may also not be part of a limb, but part of the body, such as the abdomen. The majority of individuals with both phantom limb and dysesthesia experience painful sensations.
Phantom pain
There are many different treatment options for phantom limb pain that are actively being researched. Most treatments do not take into account the mechanisms underlying phantom pains, and are therefore ineffective. However, there are a few treatment options that have been shown to alleviate pain in some patients, but these treatment options usually have a success rate less than 30%. It is important to note that this rate of success does not exceed the placebo effect. It is also important to note that because the degree of cortical reorganization is proportional to phantom limb pains, any perturbations to the amputated regions may increase pain perception.
Pain in invertebrates
Invertebrate nervous systems are very unlike those of vertebrates and this dissimilarity has sometimes been used to reject the possibility of a pain experience in invertebrates. In humans, the neocortex of the brain has a central role in pain and it has been argued that any species lacking this structure will therefore be incapable of feeling pain. However, it is possible that different structures may be involved in the pain experience of other animals in the way that, for example, crustacean decapods have vision despite lacking a human visual cortex.
Two groups of invertebrates have notably complex brains: arthropods (insects, crustaceans, arachnids, and others) and modern cephalopods (octopuses, squid, cuttlefish) and other molluscs. The brains of arthropods and cephalopods arise from twin parallel nerve cords that extend through the body of the animal. Arthropods have a central brain with three divisions and large optic lobes behind each eye for visual processing. The brains of the modern cephalopods in particular are highly developed, comparable in complexity to the brains of some vertebrates (See also: Invertebrate brains). Emerging results suggest that a convergent evolutionary process has led to the selection of vertebrate-like neural organization and activity-dependent long-term synaptic plasticity in these invertebrates. Cephalopods stand out by having a central nervous system that shares prime electrophysiological and neuroanatomical features with vertebrates like no other invertebrate taxon.
Phantom pain
Phantom pain sensations are described as perceptions that an individual experiences relating to a limb or an organ that is not physically part of the body. Limb loss is a result of either removal by amputation or congenital limb deficiency. However, phantom limb sensations can also occur following nerve avulsion or spinal cord injury.
History of pain theory
The use of fMRI to study brain activity confirms the link between visual perception and pain perception. It has been found that the brain regions that convey the perception of pain are the same regions that encode the size of visual inputs. One specific area, the magnitude-related insula of the insular cortex, functions to perceive the size of a visual stimulation and integrate the concept of that size across various sensory systems, including the perception of pain. This area also overlaps with the nociceptive-specific insula, part of the insula that selectively processes nociception, leading to the conclusion that there is an interaction and interface between the two areas. This interaction tells the individual how much relative pain they are experiencing, leading to the subjective perception of pain based on the current visual stimulus.
Scotoma
Beyond its literal sense concerning the visual system, the term "scotoma" is also used metaphorically in several fields, including neurology, neuropsychology, psychology, philosophy, and politics. The common theme of all the figurative senses is of a gap not in visual function but in the mind's perception, cognition, or world view. Their concrete connection to the literal sense, however, is by the connection between the nervous system and the mind, via the chain of links from sensory input, to nerve conduction, to the brain, to perception (the processing and interpreting of that input) via the brain-mind correlation, to psychological function. Thus there is not only (or not necessarily) a visual inability to see an aspect of reality but also (or instead) a mental inability to conceive even the possibility of seeing that aspect, due to a cognitive schema that lacks any provision for it.
At the most concrete level, there is neuropsychological scotoma. One example is the hemispatial neglect that is sometimes experienced by people who have had strokes. Another type is the phenomenon of reverse or negative phantom limb, in which nerve injuries to the limbs, such as trauma in which a limb's nerves are severed but the limb is spared from amputation, can affect the mind's body schema in such a way that an existing limb seems to its owner like it should not exist, and its presence thus seems uncanny. Neurologist Oliver Sacks, who experienced a reverse phantom leg that later resolved, considered it a form of spatial neglect in the body schema analogous to hemispatial neglect in that the mind could not conceive of the leg as self because it could not conceive that there was any space for the leg to exist in. Sacks and others agreed that the leg thus seemed like someone else's leg, including sometimes a cadaverous one, which was part of the reason for the dysphoria but not the sole explanation. Even for people who intellectually understood that the leg or hand was supposed to be theirs simply could not believe it emotionally and could not completely reconcile reality with schema, prompting great unease. Given how hard this is to comprehend for a person who has not experienced it, people recently experiencing it for the first time consider it both uncanny and ineffable (as Sacks self-reported and found in others). Sacks also explored the regular type of phantom limb (a positive phantom), which does not produce a neuropsychological scotoma but shares with reverse phantoms the trait that the body schema resists revision despite a person's perfect intellectual awareness and acceptance of the current physical reality (that is, that the amputated limb is gone or that the spared limb is still present). This suggests that aspects of schema in the mind (body schema, world schema) have neurologic bases that cannot be revised by mere intellectual understanding—at least not quickly. Sacks does explore the topic of how people adapt to phantoms over the years and how positive phantom limbs often gradually foreshorten and sometimes disappear; but some remain for the rest of life.
At a higher level of abstraction are what have been called , in which a person's self-perception of his or her own personality is judged by others to have a gap in perceptive ability. Thus, in psychology, "scotoma" can refer to a person's inability to perceive personality traits in themselves that are obvious to others. And at the highest abstraction level are what have been called intellectual scotomas, in which a person cannot perceive distortions in their world view that are obvious to others. Thus, in philosophy or politics, a person's thoughts or beliefs might be shaped by an inability to appreciate aspects of social interaction or institutional structure.
Pain in cephalopods
Sometimes a distinction is made between "physical pain" and "emotional" or "psychological pain". Emotional pain is the pain experienced in the absence of physical trauma, e.g. the pain experienced by humans after the loss of a loved one, or the break-up of a relationship. It has been argued that only primates and humans can feel "emotional pain", because they are the only animals that have a neocortex – a part of the brain's cortex considered to be the "thinking area". However, research has provided evidence that monkeys, dogs, cats and birds can show signs of emotional pain and display behaviours associated with depression during painful experience, i.e. lack of motivation, lethargy, anorexia, unresponsiveness to other animals.
Pain
The prevalence of phantom pain in upper limb amputees is nearly 82%, and in lower limb amputees is 54%. One study found that eight days after amputation, 72% of patients had phantom limb pain, and six months later, 67% reported it. Some amputees experience continuous pain that varies in intensity or quality; others experience several bouts of pain per day, or it may reoccur less often. It is often described as shooting, crushing, burning or cramping. If the pain is continuous for a long period, parts of the intact body may become sensitized, so that touching them evokes pain in the phantom limb. Phantom limb pain may accompany urination or defecation.
Pain in crustaceans
Sometimes a distinction is made between "physical pain" and "emotional" or "psychological pain". Emotional pain is the pain experienced in the absence of physical trauma, e.g. the pain experienced by humans after the loss of a loved one, or the break-up of a relationship. It has been argued that only primates and humans can feel "emotional pain", because they are the only animals that have a neocortex – a part of the brain's cortex considered to be the "thinking area". However, research has provided evidence that monkeys, dogs, cats and birds can show signs of emotional pain and display behaviours associated with depression during painful experience, i.e. lack of motivation, lethargy, anorexia, unresponsiveness to other animals.
Neuropathic pain
Up to 7%-8% of the European population is affected, and in 5% of persons it may be severe.
Neuropathic pain may result from disorders of the peripheral nervous system or the central nervous system (brain and spinal cord). Thus, neuropathic pain may be divided into peripheral neuropathic pain, central neuropathic pain, or mixed (peripheral and central) neuropathic pain.
Central neuropathic pain is found in spinal cord injury, multiple sclerosis, and some strokes. Aside from diabetes (see diabetic neuropathy) and other metabolic conditions, the common causes of painful peripheral neuropathies are herpes zoster infection, HIV-related neuropathies, nutritional deficiencies, toxins, remote manifestations of malignancies, immune mediated disorders and physical trauma to a nerve trunk. Neuropathic pain is common in cancer as a direct result of cancer on peripheral nerves (e.g., compression by a tumor), or as a side effect of chemotherapy (chemotherapy-induced peripheral neuropathy), radiation injury or surgery.
Nerve allograft
In a trauma or surgical resection, a nerve can be damaged, which is called a nerve defect. This defect needs to be repaired in order to regain full or partial sensory and motor function.
Peripheral nerve injury is a major clinical problem and can result in neuropathic pain, which is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.
Damaged nerve fibers continuously excite electric pulses, inducing pain or abnormal sensation dysesthesia. It has been shown that in allograft surgeries, post-operative neuropathic pain was present in some patients, but only if they suffered from this condition pre-operatively. Patients without neuropathic pain before their surgery did not complain about neuropathic pain afterwards. Hence, allograft treatment does not seem to be a risk factor for this specific problem.
Phantom limb
Phantom limb pain (PLP) is a complex phenomenon that includes a wide variety of symptoms ranging from tingling and itching to burning and aching.
Electroanalgesia
The use of peripheral nerve stimulation, or PNS, for the relief of chronic pain states was first reported over 30 years ago. Recent studies have demonstrated that electrical stimulation of nerves leads to inhibitory input to the pain pathways at the spinal cord level. PNS is most effective in the treatment of neuropathic pain (e.g., posttraumatic neuropathy, diabetic neuropathy) when the nerve lesion is distal to the site of stimulation.
Tactile hallucination
Cenesthopathy is a rare medical term used to refer to the feeling of being ill and this feeling is not localized to one region of the body. Cenesthopathic hallucinatory experiences are caused by the hyperactive neuronal stimulation of the primary somatosensory cortex due to a disorder or a damage to this area. There are two theories that are established to portray sensation of unified bodily feeling. One of these theories is called associationism, which states that cenesthesia is an amalgamation of propioceptive and interoceptive sensations. Faculty psychology is the other theory which states that there is a particular brain region where all of the sensory information converged and the integration of this information gives one cenesthetic sensation. The latter theory became more predominant and it established two types of cenestopathic hallucinations namely "painful" and "paraesthetic". Patients that experience "painful" type of cenesthopathic hallucination felt that their organs were stretched apart and twisted. On the other hand, patients with "paraesthetic" cenesthopathic hallucination experience severe hallucinatory itching.
Phantom pain
Age and gender have not been shown to affect the onset or duration of phantom limb pain. Although it has not been fully explored, one investigation of lower limb amputation observed that as stump length decreased, there was a greater incidence of moderate and severe phantom pain.
Parasympathetic nervous system
General visceral afferent sensations are mostly unconscious visceral motor reflex sensations from hollow organs and glands that are transmitted to the CNS. While the unconscious reflex arcs normally are undetectable, in certain instances they may send pain sensations to the CNS masked as referred pain. If the peritoneal cavity becomes inflamed or if the bowel is suddenly distended, the body will interpret the afferent pain stimulus as somatic in origin. This pain is usually non-localized. The pain is also usually referred to dermatomes that are at the same spinal nerve level as the visceral afferent synapse.
Psychogenic pain
Sufferers are often stigmatized, because both medical professionals and the general public tend to think that pain from psychological source is not "real". However, specialists consider that it is no less actual or hurtful than pain from other sources.
Phantom limb
Not all scientists support the hypothesis that phantom limb pain is the result of maladaptive changes in the cortex. Pain researchers such as Tamar Makin (Oxford) and Marshall Devor (Hebrew University, Jerusalem) argue that phantom limb pain is primarily the result of "junk" inputs from the peripheral nervous system.
Occipital nerve stimulation
The history of PNS is thoroughly reported by Slavin, 2011. The use of PNS for chronic pain was first reported in 1967 by Wall and Sweet although the first implantations were performed in 1962 by Shelden. They demonstrated that electrical stimulation of peripheral nerves suppresses the perception of pain. A period of semi-experimental PNS usage continued for 15 – 20 years. During the latter half of the 1980s, PNS became an established surgical procedure. In the late 1990s, Weiner and Reed reported the percutaneous technique of inserting electrodes in the vicinity of the occipital nerves to treat occipital neuralgia. Weiner showed that placing a PNS electrode close to a nerve is effective for pain relief and a technically simple procedure. This pioneering work heralded the start of the modern era of PNS. It was 2003 before Popeney and Aló proposed using PNS for the treatment of chronic migraine. Subsequently, prospective randomized controlled trials were launched to gather additional clinical evidence.