Release of neurotransmitters in the CNS by spinal cord stimulation: survey of present state of knowledge and recent experimental studies.

Electric stimulation applied to the posterior surface of the spinal cord (SCS) is an established treatment in certain chronic pain syndromes resistant to conventional therapeutic procedures. Despite the clinical value of SCS, the mechanisms behind the efficacy of the method are largely unknown. Several neurotransmitters in the CNS (e.g. opioids, serotonin, noradrenaline, substance P, GABA), have been proposed to be involved in the pain-alleviating effect of SCS. However, as yet there is no evidence that these would be involved in the beneficial effects of SCS. We have studied neurotransmitter release, using microdialysis techniques, in the spinal dorsal horn and the periaqueductal grey substance (PAG) of the rat and the cat, induced by SCS applied with current parameters equivalent to those used clinically in man. Up to now dialysates have been assayed for GABA, serotonin and substance P with highly sensitive methods. Three groups of studies have been carried out: (1) dorsal horn microdialysis in rats under halothane anesthesia during acute SCS; (2) dorsal horn microdialysis in cats under barbiturate anesthesia or following decerebration, and (3) PAG microdialysis in awake, unrestrained rats with chronic SCS. In the dorsal horn studies, microdialysis probes of different sizes were implanted in the lower lumbar dorsal horns. In the PAG studies, rats had guide cannulas for microdialysis stereotactically inserted into the PAG. SCS was applied at a low thoracic level with 50 or 100 Hz; 0.2 ms and an intensity amounting to 2/3 of the motor threshold. The microdialysis probes were perfused with modified Ringer's solution. Fractions of the dialysate were collected at various intervals. GABA and serotonin were assayed by reverse-phase HPLC, while substance P was investigated using a highly sensitive radioimmunoassay. SCS induced a significant release of GABA in the dorsal horn, most marked in the fraction following the stimulation period. In the rats with PAG microdialysis, the GABA level decreased significantly following two stimulation periods, although transitional increases during SCS were noted in some animals. In the decerebrated cat, a significant release of serotonin in the dorsal horn was obtained with SCS, while the levels of the metabolite 5-HIAA were little influenced by stimulation. On the contrary, in the decerebrated preparation there was no release of substance P in the dorsal horn with SCS, although in the intact cat under barbiturate anesthesia a significant release was induced.4+ off