INFLAMMATION INCREASES THE DISTRIBUTION OF DORSAL HORN NEURONS THAT INTERNALIZE THE NEUROKININ-1 RECEPTOR IN RESPONSE TO NOXIOUS AND NONNOXIOUS STIMULATION

Although the neurokinin-1 (NK-1)/substance P (SP) receptor is expresse d by neurons throughout the spinal dorsal horn, noxious chemical stimu lation in the normal rat only induces internalization of the receptor in cell bodies and dendrites of lamina I. Here we compared the effects of mechanical and thermal stimulation in normal rats and in rats with persistent hindpaw inflammation. Electron microscopic analysis confir med the upregulation of receptor that occurs with inflammation and dem onstrated that in the absence of superimposed stimulation, the increas ed receptor was, as in normal rats, concentrated on the plasma membran e. In general, noxious mechanical was more effective than noxious ther mal stimulation in inducing NK-1 receptor internalization, and this wa s increased in the setting of inflammation. Although a 5 sec noxious m echanical stimulus only induced internalization in 22% of lamina I neu rons in normal rats, after inflammation, it evoked near-maximal (98%) internalization in lamina I, produced significant changes in laminae I II-VI, and expanded the rostrocaudal distribution of neurons with inte rnalized receptor. Even non-noxious (brush) stimulation of the inflame d hindpaw induced internalization in large numbers of superficial and deep neurons. For thermal stimulation, the percentage of cells with in ternalized receptor increased linearly at >45 degrees C, but in normal rats, these were restricted to lamina I. After inflammation, however, the 52 degrees C stimulus also induced internalization in 25% of lami nae III-IV cells. These studies provide a new perspective on the reorg anization of dorsal horn circuits in the setting of persistent injury and demonstrate a critical contribution of SP.