Involvement of substance P in hyperalgesia induced by intrathecal galanin

Previously we have demonstrated that an intrathecal injection of galanin (GAL) decreases the nociceptive threshold for mechanical stimulation without effect on thermal nociceptive responses. The present experiments were conducted to determine whether substance P (SP) would be involved in such a decrease in the nociceptive threshold produced by GAL. An intrathecal injection of anti-SP monoclonal antibody inhibited the nociceptive threshold-decreasing effect of intrathecal GAL (0.1 nmol/rat). This antibody significantly suppressed the contractile action of SP (3 nM) on the longitudinal muscle and that of neurokinin A (3 nM) to a lesser degree. Binding of [125I]Tyr8-SP to this antibody was inhibited by SP in a concentration-dependent manner in the range 0.1-33 nM without suppression by GAL at a concentration of 3300 nM. In addition, an intrathecal injection of the anti-SP monoclonal antibody increased the nociceptive threshold for mechanical stimulation in carrageenin-inflamed rats without effect on thermal nociceptive behaviors. The capsaicin (0.5 microM)-evoked release of immunoreactive SP from dorsal-half slices of the spinal cord was increased by galanin (1 microM, but not 0.1 microM) without effects on basal release. An intrathecal injection of GAL did not produce aversive responses (biting, licking and scratching) at doses of 0.1 and 1 nmol/rat. GAL (0.1 nmol/rat) did not affect biting/licking behaviors evoked by SP (1 nmol/rat), but inhibited SP-evoked scratching behavior. These results suggest that the nociceptive threshold-decreasing action of intrathecal GAL is at least in part mediated by SP, and that GAL may act on primary afferent terminals to increase the release of SP evoked by stimulation.