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

Abstract

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.