Mechanisms of spinal cord stimulation in neuropathic pain

The understanding of the mode of action of spinal cord stimulation (SCS) as treatment of neuropathic pain is still fragmentary. SCS evolved from the g ate-control theory postulating a spinal modulation of noxious inflow, but t here is little evidence that SCS influences nociceptive pain; pain relief i n peripheral vascular disease and angina pectoris is presumably secondary t o other SCS effects. In man, SCS may effectively abolish both continuous an d evoked pain (tactile/thermal allodynia) whereas induced, acute nociceptiv e pain is unaffected. Recent SCS studies performed on rat models of mononeu ropathy have demonstrated a preferential effect on AP fiber mediated functi ons, and the hyperexcitability of wide-dynamic-range dorsal horn neurons wa s attenuated. These effects were coupled to increased release of GABA and r educed glutamate and aspartate release in the dorsal horn. Intrathecal admi nistration of GABA, baclofen and adenosine enhanced the SCS effect on tacti le allodynia even in previously non-responsive rats. Preliminary results in dicate that gabapentin may have a similar effect. GABAergic and adenosine-r elated mechanisms conceivably represent only examples of a number of putati ve receptor systems involved in SCS. Clinical trials have been initiated ex ploring the possibility to improve the efficacy of SCS by concomitant pharm acotherapy.