Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA (2002) Lack of capsaicin (CAP)-evoked sensitization following SP-SAP treatment is not attributed to decreased CAP-evoked exciataion. Neuroscience 2002 Abstracts 351.24. Society for Neuroscience, Orlando, FL.
Summary: The depletion of SPR+ neurons in the spinal cord by substance P-saporin conjugate (SP-SAP) prevents the development of central sensitization, induced by capsaicin (CAP). SP-SAP treatment causes a dramatic decrease in CAP-evoked excitation of remaining nociceptive neurons. The lack of central sensitization after SP-SAP may be due to the decreased excitation of these neurons by CAP. We therefore compared excitation and sensitization following intraplantar injection of different doses of CAP (10 and 100 μg) in rats pretreated intrathecally with vehicle (VEH) or SP-SAP. Injection of 10μg or 100 μg CAP evoked activation and sensitization of nociceptive neurons in VEH-treated rats. Mean responses to von Frey stimuli doubled and heat threshold decreased by about 6˚ C. In SP-SAP rats, 10 μg CAP evoked excitation that was <60% of control whereas 100 μg CAP evoked excitation that was similar to control values. However, sensitization failed to occur following either dose of CAP. In addition, we examined whether effects of SP-SAP was mediated by descending modulation. Transsection of the dorsolateral funiculus increased spontaneous activity of nociceptive neurons in rats pretreated with VEH, but not with SP-SAP. Our data show that the development of central sensitization is dependent on neurons that possess the SPR, and that these neurons appear to be part of a supraspinal loop that modulates descending tonic inhibition.
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