Peripheral inflammation alters desensitization of substance P-evoked current in rat dorsal root ganglion neurons

The neuropeptide substance P is synthesized in a proportion of neurons of the peripheral and central nervous system, and the receptor for substance P, tachykinin NK1 receptor, has been identified in numerous areas of the central nervous system including the spinal cord. The present investigation was to confirm the existence of tachykinin NK1 receptor on rat dorsal root ganglion (DRG) neurons and characterize the adaptation of inward current evoked by substance P during carrageenan-induced peripheral inflammation. Using whole-cell voltage recording technique, our results demonstrated that 1 μM substance P elicited significant inward current in a small population of small-diameter DRG neurons of control rats (7%, n = 218) and in a bigger proportion of DRG neurons of carrageenan-inflamed rats (15%, n = 203). Desensitization of substance P-evoked current was exhibited in almost all of substance P-responsive DRG neurons in control rats (94%, n = 16), while it diminished in a bigger proportion of DRG neurons (35%, n = 31) in inflamed rats. Furthermore, desensitization of substance P-evoked current was recovered by the activation of protein kinase C (PKC) by application of phorbol 12,13-dibutyrate, a selective agonist of PKC, in the DRG neurons of the inflamed rats. All these results indicated that tachykinin NK1 receptor in the primary afferents might contribute to the development and maintenance of inflammatory pain.