Mechanisms of action of spinal cord stimulation in complex regional pain syndromes:: Present state of research and the future

Spinal cord stimulation (SCS) was a clinical spin-off from the Gate-Control theory by Melzack and Wall, launched in 1965. The main indication has been neurogenic pain conditions, and although SCS during the last decades has proven effective also for ischemic nociceptive pain, neuropathic pain of peripheral origin (nerve and root lesions) remains the most important indication. Not rarely the pain is accompanied by signs of dysautonomia leg oedema, rubor, pathologic perspiration, temperature changes) with a predilection for the distal part of the extremities. In these pain states, now labelled "complex regional pain syndromes (CRPS) type I and II", pathologic changes of sympathetic function has been hypothesized. SCS may be effective both in neuropathic pain with and without dysautonomia, but between 30-40% of selected cases fail to report a positive effect. The reason is unknown. Animal studies indicate that SCS releases substance P, serotonin, noradrenalin, glycin and GABA in the dorsal horns (DH). Activation of the CABA-B receptor may be linked to decrease of pathologic glutamate release in neuropathic pain. Also adenosine A-1 receptor-related mechanisms may be involved. Furtmermore, SCS may suppress sympathetic activity by central actions on efference via nicotinic receptors on the ganglionic level and mainly alpha -1 adrenoreceptors in the periphery. With higher SCS intensity - and maybe also with medium/low - antidromic mechanims with a peripheral release of CGRP - dependent on the presence of NO -, may contribute to peripheral vessel dilatation and warming. All these changes may participate in the beneficial effects of SCS in CRPS. The paper is ended with a discussion of future lines of research and method development.