Thus it appears that the central effects of a painful condition are determined by many ascending and descending systems using a variety of transmitters. Some aspects of opiate addiction and also the discomfort that follows withdrawal of the drug might also be accounted for in this way. Indeed, it is known that some of these peptides not only relieve pain but suppress withdrawal symptoms.
It should be noted that the descending pain-control systems contain, in addition to opiate connections, noradrenergic and serotonergic influences as well. A descending norepinephrine-containing pathway, as mentioned, has been traced from the locus ceruleus in the dorsolateral pons to the spinal cord, and its activation blocks spinal nociceptive neurons. The rostroventral medulla contains a large number of serotonergic neurons from which descending fibers inhibit dorsal horn cells concerned with pain transmission, perhaps providing a rationale for the use of certain antidepression serotonin agonist medications in patients with chronic pain.
Finally, there is remodeling of the types and densities of surface receptors in the posterior horns as a result of nerve injury. These changes alter the effects of the above mentioned secondary modulating systems on pain pathways. This assumes importance in states of chronic pain after somatic and neural injury as discussed in the next sections.
Several terms related to the experience of altered sensations and pain are often used interchangeably but each has specific meaning. Hyperesthesia is a general term for heightened cutaneous sensitivity. The term hyperalgesia refers to an increased sensitivity and a lowered threshold to painful stimuli. Inflammation and burns of the skin are common causes of hyperalgesia. The term hypalgesia, or hypoalgesia, refers to the opposite state—that is, a decreased sensitivity and a raised threshold to painful stimuli. A demonstrable reduction in pain perception (i.e., an elevated threshold) associated with an increased reaction to the stimulus once it is perceived, is sometimes referred to as hyperpathia (subtly different from hyperalgesia). In this circumstance there is an excessive reaction to all stimuli, even those (such as light touch) that normally do not evoke pain, a symptom termed allodynia. The elicited allodynic pain may have unusual features, outlasting the stimulus and being diffuse, modifiable by fatigue and emotion, and often being mixed with other sensations. The mechanism of these abnormalities is not clear but both hyperpathia and allodynia are common features of neuropathic or neurogenic pain, such as the pain generated by peripheral neuropathy. These features are also exemplified by causalgia, a type of burning pain that results from interruption of a peripheral nerve (see “Causalgia and Reflex Sympathetic Dystrophy”).
As indicated earlier, the nerve endings in each tissue are activated by different mechanisms, and the pain that results is characterized by its quality, locale, and temporal attributes. Skin pain is of two types: a pricking pain, evoked immediately on penetration of the skin by a needle point; or a stinging or burning pain that follows in a second or two. Together they constitute the “double response” of Lewis. Both types of dermal pain can be localized with precision. Compression of nerves by the application of a tourniquet to a limb abolishes pricking pain before burning pain because large fibers are more susceptible to pressure. The first (fast) pain is transmitted by the larger (A-d) fibers and the second (slow) pain, which is somewhat more diffuse and longer lasting, by the thinner, unmyelinated C fibers.