Inhibition of Primate Spinothalamic Tract Neurons by Spinal Glycine and GABA Is Reduced During Central Sensitization. LIN, QING, YUAN BO PENG AND WILLIAM D. WILLIS. Department of Anatomy and Neurosciences, Marine Biomedical Institute, The University of Texas Medical Branch, Galveston, TX 77555-1069, U.S.A..
APStracts 3:0067N, 1996.
1. In our previous work, we demonstrated that the glycinergic and GABAergic mechanisms that help mediate the descending inhibition from the periaqueductal gray exert a tonic modulation of nociceptive inputs through spinal glycine and GABA receptors. This study was designed to examine further possible changes in the inhibition of the activity of spinothalamic tract (STT) neurons mediated by spinal glycine and GABA receptors when STT cells are sensitized by intradermal injection of capsaicin and to investigate the role of the protein kinase C (PKC) system in the functional modulation of these receptors. 2. While the responses of STT cells to cutaneous mechanical stimuli were sensitized by intradermal injection of capsaicin, the inhibition of the responses of all STT cells tested to noxious cutaneous stimuli produced by iontophoretic release of glycine and GABA was significantly attenuated. The inhibition elicited by iontophoretic application of a GABA A agonist, muscimol, was reduced in some of the cells tested. 3. When the spinal cord dorsal horn was pretreated with a selective PKC inhibitor, NPC15437, by microdialysis, sensitization of STT cells by capsaicin injection and the accompanying attenuation of glycine- and GABA-induced inhibition were prevented. 4. Sensitization of STT cells to cutaneous mechanical stimuli was also induced by administration of the PKC activator, 12- O - tetradecanoylphorbol-13-acetate, into the spinal dorsal horn. The inhibition produced by iontophoretic release of glycine, GABA and muscimol was found to be reduced in most cells examined when this phorbol ester was used. An inactive phorbol ester, 4 [alpha] -phorbol 12,13-didecanoate, did not produce significant effects on cellular activity. 5. These results suggest that there is an activation of PKC in the spinal cord when STT neurons are sensitized following intradermal injection of capsaicin or administration of phorbol ester. This sensitization is likely to be involved in the development of allodynia and secondary hyperalgesia not only by enhancing the responses of excitatory amino acid receptors but also by desensitizing glycine and GABA receptors.

Received 1 December 1995; accepted in final form 13 March 1996.
APS Manuscript Number J814-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 April 96