Spinal Cord Synaptic Plasticity and Chronic Pain

T he word “pain” encompasses several phenomena, which probably have several different mechanisms. Immediately after a noxious stimulus there comes an initial, short-lasting component of pain, which is described well by the gate-control theory. A little later comes a slow-onset, long-lasting component mediated by C-fibers from deep tissue, if that has been injured. This may be combined with sensitization of peripheral receptors and their continued activation by products of peripheral inflammatory processes. Relatively rarely, a pathologic state of chronic pain may develop, which can involve more or less permanent changes in the central nervous system (CNS), persisting long after the original injury has healed(l). Various forms of synaptic plasticity that may underlie these pathologic CNS changes are the subject of this review. There has been much interest recently in the involvement of spinal cord synaptic plasticity in the hyperalgesia and allodynia of chronic pain syndromes (2,3). Several forms of activity-dependent plasticity have been described in the spinal cord. Well established cases that have been widely associated with chronic pain are “windup” (4), which lasts seconds to minutes, and increases (5,6) or decreases (7) in the excitability of spinal reflexes lasting 1 to 3 h. More recently, long-term potentiation and depression of synaptic transmission, of the same types that occur in the hippocampus and neocortex (where they have been shown to last for days), have also been described in several regions of the spinal cord (8-10). Until now, there has been little cross-fertilization between the literature on spinal cord changes concerned with chronic pain and that on long-term potentiation and depression. It is, therefore, useful to summarize very briefly what is known of the mechanisms of these various forms of physiologic plasticity in such a way as to allow comparison between them and to clarify similarities and differences.