SPINAL-CORD SUBSTANCE-P RECEPTOR IMMUNOREACTIVITY INCREASES IN BOTH INFLAMMATORY AND NERVE INJURY MODELS OF PERSISTENT PAIN

Numerous studies have implicated the primary afferent derived neuropep tide, substance P, which exerts its effects via the neurokinin-1/subst ance P receptor, in the transmission of nociceptive messages at the le vel of the spinal cord. Immunocytochemical studies demonstrate that th e substance P receptor is concentrated in neurons of lamina I of the s uperficial dorsal horn. Since alterations in the number and distributi on of the receptor may underlie persistent pain conditions, we have us ed immunocytochemistry to study the distribution of the receptor in tw o very different rat models of persistent pain: chronic inflammation, which is associated with increased levels of substance P, and sciatic nerve section, which is associated with decreased levels of substance P in the dorsal horn. Inflammation was produced by unilateral hindpaw injection of complete Freund's adjuvant. We report that there is an up -regulation of substance P receptor immunoreactivity in the superficia l laminae of the dorsal horn in both injury models. The increase was f ound at all time points studied (up to one week after induction of inf lammation and up to two weeks after sciatic nerve section). The increa se in substance P receptor immunoreactivity was not only present in th e medial part of the dorsal horn at segment L4, which is the region of input of the afferents from the hindpaw, but also in the lateral part s of the dorsal horn, and at segments rostral (L1) and caudal (S1) to the afferent input from the hindpaw. These results indicate that the u p-regulation of the receptor is not predictable merely by the change i n the concentration of substance P in the dorsal horn. Furthermore, th e non topographic up-regulation of substance P receptor in these diffe rent conditions may contribute to the central sensitization of dorsal horn nociceptors under conditions of persistent pain.