Khasabov SG, Rogers SD, Mantyh PW, Simone DA (2000) Responses of spinal dorsal horn neurons to capsaicin following intrathecal pretreatment with substance p-saporin toxin. Neuroscience 2000 Abstracts 635.13. Society for Neuroscience, New Orleans, LA.
Summary: Intrathecal (i.t.) application of the cytotoxic substance P-saporin (SP-SAP) conjugate is internalized by dorsal horn neurons expressing the SP receptor (SPR) and results in loss of SPR-expressing neurons. Loss of SPR+ neurons attenuates the nocifensive behavior and hyperalgesia produced by intraplantar injection of capsaicin (CAP). Here we determined the effect of SP-SAP on CAP-evoked excitation and sensitization of dorsal horn neurons to heat and mechanical stimuli. Separate groups of rats were given i.t. injection of vehicle (VEH) or SP-SAP (5´10-6mM in 10ml) 10 or 30 days prior to electrophysiological experiments. Extracellular recordings were obtained from nociceptive dorsal horn neurons classed as high threshold (HT) or wide dynamic range (WDR). Responses to mechanical (von Frey monofilaments) and heat (35°C-51°C) stimuli were obtained before and after injection of 10 mg CAP into the receptive field. In VEH-treated animals, CAP produced an intense activation of HT and WDR neurons with a mean peak discharge rate of 52.2±11.2 Hz. In addition, the mean number of impulses evoked by mechanical stimuli increased 267±33% following CAP and mean heat thresholds decreased from 44.7±1.6°C to 37.7±0.7°C. In SP-SAP treated animals, however, the peak response evoked by CAP was decreased by 61±11% as compared to control. Moreover, CAP did not significantly alter responses to mechanical or heat stimuli. These data suggest that dorsal horn neurons that possess the SPR play a critical role in the development of sensitization to mechanical and heat stimuli following CAP.
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