Differential responses of pronociceptive neurons in the rostral ventromedial medulla during acute capsaicin-evoked visceral and somatic hyperalgesia

Pro-nociceptive Rostral Ventromedial Medulla (RVM) neurons have been proposed to be involved in the generation of hyperalgesic states during somatic inflammation but their possible role in visceral hyperalgesia is unknown. Here we have compared the nociceptive behaviour of rats following peripheral application of capsaicin (CAP) either intracolonic(IC) or intradermal(ID). Electrophysiological experiments were also conducted to explore the role of RVM pro nociceptive “ON” cells in the maintenance of somatic and visceral hyperalgesic states. In behavioural experiments, the mechanical sensitivity of the abdomen and hindpaw was tested in rats (von Frey test) before and after IC or ID CAP to assess hyperalgesia. In the electrophysiological experiments, recordings from RVM “ON” cells were made. Neurons were identified as “ON” cells if they increased their firing rate in response to noxious stimuli: pinch, heat and colorectal distension. After characterization, CAP or saline was instilled IC or injected ID, and the test noxious stimuli were applied again. IC CAP evoked spontaneous pain behaviours lasting more than 10 minutes after the injection but were much shorter when CAP was applied ID. Also, IC CAP induced hyperalgesia in the abdominal skin. ID CAP induced a hyperalgesia of the paw that lasted for only 10 minutes. Intracolonic CAP evoked an increase in the firing of “ON” cells that remained significantly higher for over 60 minutes. Noxious stimuli applied to the colon or to either hindpaw during this time significantly increased the firing of the cells. ID CAP evoked an increase in the firing of “ON” cells that lasted only for a few minutes after the injection. Noxious stimuli applied did not induce further increases in the firing of the cells. We conclude that the sustained responses of RVM “ON” cells following IC CAP could contribute to the prolonged central hyperexcitability induced by a visceral noxious stimulus.