INVOLVEMENT OF ENDOGENOUS OPIOIDS IN THE ANALGESIC EFFECT OF SUBSTANCE P AT SUPRASPINAL LEVEL

Substance P (SP) and its neurokinin 1 (NK1) receptor, are widely distributed through the peripheral and central nervous systems, where they are involved in pain transmission. Although SP is thought to have excitatory actions and promote nociception in the spinal cord, when supraspinally injected the peptide induces analgesia. Altered pain states, such as those caused by nerve injury and inflammation, are associated with allodynia (pain to non-noxious stimuli) and hyperalgesia (increased pain to noxious stimuli). It has been suggested that supraspinal SP/NK1 receptor system is modified in chronic pain. To this regard we evaluated the role of supraspinal SP and NK1 receptor in inflammatory pain induced by injection of carrageenan in the hind-paw of the rat. Moreover, because the NK1 receptor colocalizes with the MOP receptor at supraspinal sites involved in pain modulation, we decided to study the possible involvement of the opioid system on SP-induced effects. Intracerebroventricular SP clearly showed inhibition of allodynia and hyperalgesia. Pretreatment with the selective NK1 antagonist L-733,060 and the opioid antagonist naloxone blocked the SP-induced effects also when SP was administered after the carrageenan injection. These results suggest the involvement of supraspinal NK1 in inflammatory pain possibly mediated by the release of endogenous opioids.