Abstract
Experiments with selective antagonists for the tachykinin receptors (especially NK 1 and NK2), and with knockout (KO) mice with disruptions of the genes encoding for substance P and neurokinin A or the NK 1 receptor have shown that the tachykinins play a role in nociceptive processing, especially in pain and hyperalgesia related to chemical and inflammatory stimuli. We have examined the role of the tachykinins in pain and hyperalgesia induced by chemical stimulation of viscera. We reasoned that clear identification of the functional role of the tachykinins should be simpler in the visceral system, since almost all visceral afferents (>99%) contain peptides, and a high proportion contain tachykinins.
We have observed that NK 1 receptor KO mice show normal responses to mechanical visceral stimuli, but show deficits in responses to some but not all types of chemical or inflammatory visceral stimuli compared to wild-type mice. They also do not develop normal primary visceral hyperalgesia. In a separate study, we used an NK2 receptor antagonist and observed a dose-dependent inhibition of the enhanced responses of dorsal horn neurones to colorectal distension after inflammation. This antagonist had no effect on responses to distension of the normal colon or to pelvic nerve stimulation, suggesting a peripheral action specific to the sensitized colon.
We conclude that the tachykinins play an important role in the generation of visceral hyperalgesic states at both peripheral and central levels. These results provide a neurophysiological basis for a possible use of tachykinin receptor antagonists in functional pain disorders of internal organs.
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Cervero, F., Laird, J.M.A. (2000). Tachykinins in Visceral Pain and Hyperalgesia. In: Saadé, N.E., Apkarian, A.V., Jabbur, S.J. (eds) Pain and Neuroimmune Interactions. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4225-4_3
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DOI: https://doi.org/10.1007/978-1-4615-4225-4_3
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