Modulation of bradykinin-induced mechanical hyperalgesia in the rat by activity in abdominal vagal afferents
Article first published online: 25 DEC 2001
European Journal of Neuroscience
Volume 10, Issue 2, pages 435–444, February 1998
How to Cite
Khasar, S. G., Miao, F. J. .-P., Jänig, W. and Levine, J. D. (1998), Modulation of bradykinin-induced mechanical hyperalgesia in the rat by activity in abdominal vagal afferents. European Journal of Neuroscience, 10: 435–444. doi: 10.1046/j.1460-9568.1998.00030.x
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Received 21 May 1997, revised 25 August 1997, accepted 2 September 1997
- cutaneous nociception;
- sympathetic decentralization sympathectomy;
- sympathetic postganglionic neurones;
Bradykinin-induced plasma extravasation and mechanical hyperalgesia are sympathetic-dependent components of inflammation. Noxious stimulation has been found to inhibit bradykinin-induced plasma extravasation by activating the hypothalamo-pituitary-adrenal axis. The sensitivity of this nociceptive-neuroendocrine feedback control of inflammation is modulated by activity in subdiaphragmatic vagal afferents. In the present study, we tested the hypothesis that activity in the subdiaphragmatic vagus also modifies bradykinin-induced mechanical hyperalgesia in the rat, using the Randall–Selitto method.
Following subdiaphragmatic vagotomy, the baseline paw-withdrawal threshold to mechanical stimulation decreased and bradykinin-induced mechanical hyperalgesia was enhanced. Mechanical hyperalgesia produced by prostaglandin E2, a direct-acting hyperalgesic agent, was not significantly affected by vagotomy. The effect of subdiaphragmatic vagotomy on bradykinin-induced hyperalgesia, but not on baseline paw-withdrawal threshold, was mimicked by coeliac branch vagotomy.
Indomethacin blocked the hyperalgesia in normal rats, but not in vagotomized rats, suggesting that bradykinin-induced hyperalgesia in normal rats is mediated by prostaglandins, whose role was unexpectedly diminished after vagotomy.
Bradykinin-induced hyperalgesia in normal rats was abolished by lumbar sympathectomy but not by sympathetic decentralization (cutting the preganglionic axons). In rats that were both vagotomized and sympathectomized, hyperalgesia induced by low-dose bradykinin was no longer present.
These results demonstrate that vagotomy induces a decrease in baseline mechanical paw-withdrawal threshold and an enhancement of bradykinin-induced mechanical hyperalgesia and suggest that these phenomena are generated by actions in peripheral tissues.