Selective ablation of mu-opioid receptor expressing neurons in the rostral ventromedial medulla attenuates stress-induced mechanical hypersensitivity.

摘要

AIMS: Chronic stress-related conditions are often associated with stress-induced hyperalgesia. However, the neural circuitry responsible for producing stress-induced hyperalgesia is not well characterized. The aim of this study was to determine the contribution of mu-opioid expressing brainstem neurons to the expression of stress-induced hyperalgesia. MAIN METHODS: The present study utilized a model of stress-induced mechanical hypersensitivity that involved application of repeated, light tactile whisker pad stimulation (WPS) in rats. Repeated WPS (10 applications/session, 4 sessions/h in 1 day, sessions on days 1-5 and 8-12) increased defensive-aggressive and hypervigilant behaviors, and produced hypersensitivity to tactile stimulation of the hind paw. In order to test the possible involvement of mu-opioid receptor expressing neurons in the rostral ventral medulla (RVM) to this response, rats received RVM microinjections of the toxin conjugate dermorphin-saporin or its control, saporin. Fourteen days later rats underwent either WPS or sham conditioning. KEY FINDINGS: Repeated WPS produced defensive-aggressive behaviors directed towards the stimulus and mechanical hypersensitivity of the hind paw that persisted for up to 2 weeks after the final WPS session. Dermorphin-saporin, but not saporin, microinjections prevented the development of hind paw mechanical hypersensitivity, but did not affect the defensive-aggressive behaviors. SIGNIFICANCE: The finding that chronic stress produces mechanical hypersensitivity through circuitry that involves the RVM provides a potential neurobiological basis for the complex interaction between chronic stress and pain.