Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity.

摘要: Tolerance to the analgesic effects of an opioid occurs after its chronic administration, a pharmacological phenomenon that has been associated with development abnormal pain sensitivity such as hyperalgesia. In present study, we examined role spinal glutamate transporters (GTs) in both morphine tolerance and thermal Chronic administered through either intrathecal boluses or continuous infusion induced dose-dependent downregulation GTs (EAAC1 GLAST) rat's superficial cord dorsal horn. This GT was mediated receptors because naloxone blocked changes. Morphine-induced reduced ability maintain vivo homeostasis at level, hyperalgesic response exogenous enhanced, including increased magnitude prolonged time course, morphine-treated rats GTs. Moreover, exhibited temporal correlation Consistently, inhibitor l-trans-pyrrolidine-2-4-dicarboxylate (PDC) potentiated, whereas positive regulator riluzole reduced, The from regulating activity by PDC were least part activation NMDA receptor (NMDAR), noncompetitive NMDAR antagonist MK-801 hyperalgesia potentiated PDC. These results indicate may contribute neural mechanisms means regional homeostasis.