The role of neurokinin 1 receptors in the maintenance of visceral hyperalgesia induced by repeated stress in rats

Background & Aims: The neurokinin 1 receptors (NK 1 Rs) and substance P (SP) have been implicated in the stress and/or pain pathways involved in chronic pain conditions. Here we examined the participation of NK 1 Rs in sustained visceral hyperalgesia observed in rats exposed to chronic psychological stress. Methods: Male Wistar rats were exposed to daily 1-hour water avoidance stress (WA) or sham WA for 10 consecutive days. We tested intraperitoneal or intrathecal injection of the NK 1 R antagonist SR140333 on the visceromotor reflex to colorectal distention in both groups at day 11. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were used to assess the expression of NK 1 Rs and/or SP in samples of colon, spinal cord, and dorsal root ganglia. Results: Both intraperitoneal and intrathecal SR140333 injection diminished the enhanced visceromotor reflex to colorectal distention at day 11 in stressed rats but did not affect the response in control animals. Real-time polymerase chain reaction and Western blotting demonstrated stress-induced up-regulation of spinal NK 1 Rs. Immunohistochemistry showed an increased number of NK 1 R-expressing neurons in the laminae I of the dorsal horn in stressed rats. The expression of NK 1 Rs was decreased in colon from stressed rats compared with control. The expression of SP gene precursor in dorsal root ganglia was unchanged in stressed rats compared with controls. Conclusions: Stress-induced increased NK 1 R expression on spinal neurons and the inhibitory effect of intrathecal NK 1 R antagonist on visceral hyperalgesia support the key contribution of spinal NK 1 Rs in the molecular pathways involved in the maintenance of visceral hyperalgesia observed after chronic WA.