Evidence that the sodium channel can generate neural pain is given by the extraordinary disease “paroxysmal extreme pain disorder” also known as “familial rectal pain syndrome.” Here, a mutation of the sodium channel gene, SCN9A, leads to the early onset of paroxysmal autonomic changes and attacks of excruciating deep burning pain in the rectum, eye, or jaw, or diffusely, as described by
Fertleman and coworkers. Similar but more diffuse painful states such as erythromelalgia and other pain disorders are being uncovered that are predicated on voltage-gated sodium channel mutations and more impressively, by the congenital absence of the ability to experience pain due to a loss of function mutation in a sodium channel gene and a mutation in the tyrosine kinase receptor gene. Fischer and Waxman provide a summary of the mutations in the sodium channel gene and their clinical presentations. Potassium channels have also been implicated in cases of severe pain, with IgG found against various components of voltage gated potassium channels (VGKC) in a series of patients with idiopathic pain often accompanied by hyperhidrosis described by Klein and colleagues. They suggested that immune suppression and antiepileptic drugs were helpful but these proposals require corroboration.
Causalgia is the name that Weir Mitchell applied to a rare (except in time of war) type of peripheral neuralgia consequent upon trauma, with partial interruption of the median or ulnar nerve and, less often, the sciatic or peroneal nerve (see also “Chronic Pain” further on and discussion in Chap. 43, Diseases of the Peripheral Nerves). It is characterized by persistent, severe pain in the hand or foot, most pronounced in the digits, palm of the hand, or sole. The pain has a burning quality and frequently radiates beyond the territory of any peripheral nerve. The painful parts are exquisitely sensitive to contact, so the patient cannot bear the pressure of clothing or drafts of air; even ambient heat, cold, noise, or emotional stimuli intensify the causalgic symptoms. The affected extremity is kept protected and immobile, often wrapped in a cloth moistened with cool water. Sudomotor, vasomotor, and, later, trophic abnormalities are usual accompaniments of the pain.
The term reflex sympathetic dystrophy (RSD) has been used to encompass several additional aspects of sustained pain after limb injury in the absence of evident damage to adjacent nerves. The current nomenclature for this syndrome is complex regional pain syndrome type 1 (CRPS I) but a plethora of terms (e.g., Sudeck atrophy of bone, minor causalgia, shoulder–hand syndrome, algodystrophy, or algoneurodystrophy) have also been used. It may also follow nontraumatic lesions of the peripheral nerves or even lesions of the CNS (“mimocausalgia”). The additional features, beyond the pain, are thinning of skin, warm surface temperature, poor nail growth, thinning of underlying bone and general disruption of thermal and vascular control. The skin of the affected part is moist and warm or cool and soon becomes shiny and smooth, at times scaly, devoid of hair, and discolored. Complex regional pain syndrome type 2 (CPRS 2), which is also referred to as causalgia, represents the same syndrome except that a history of direct injury to a peripheral nerve can be identified.