REPEATED SPINAL-CORD STIMULATION DECREASES THE EXTRACELLULAR LEVEL OFGAMMA-AMINOBUTYRIC-ACID IN THE PERIAQUEDUCTAL GRAY-MATTER OF FREELY MOVING RATS

Most of the previous experimental studies on the antinociceptive effec ts of electrical spinal cord stimulation (SCS) have focused on short-l asting effects mainly depending on spinal mechanisms. However, patient s treated with SCS for chronic pain often report pain relief exceeding the period of stimulation for several hours. The long lasting effect of SCS might not only involve spinal, but also supraspinal mechanisms. A supraspinal region of major importance for the coordination of desc ending pain inhibition is the periaqueductal grey matter (PAG). The ai m of the present microdialysis study, performed in awake freely moving rats, was to investigate if repeated SCS (two 30 min periods separate d by a 90 min resting period) alters the extracellular neurotransmitte r concentrations in the ventrolateral PAG. In a first series of experi ments significantly decreased (- 30%; P < 0.05; n = 7) gamma-aminobuty ric acid (GABA) levels were detected immediately after the second SCS session. Neither the concentration of serotonin nor that of substance P-like immunoreactivity (SP-LI) was affected by SCS. The decrease of G ABA after two SCS sessions was confirmed in a second series of experim ents (- 30%; P < 0.05; n = 7). No spontaneous decline of GABA was obse rved in sham-stimulated animals (n = 6). The glutamate concentration w as also determined in this latter series of experiments and a signific ant decrease (- 23%; P < 0.05; n = 5) was observed after the second SC S session. As GABA-neurons in the PAG exert a tonic depressive effect on the activity in descending pain inhibitory pathways, a decreased ex tracellular GABA level in this region, as detected following repeated SCS, might indicate an increased pain inhibition.