Remarkably long-lasting tachyphylaxis of pain responses to ET-1: evidence against central nervous system involvement

Canadian Journal of Physiology and Pharmacology
A Khodorova, G R Strichartz

Abstract

A profound tachyphylaxis of the acute nocifensive flinching (pain) response to subcutaneous injection of endothelin-1 (ET-1) into the hind paw footpad is shown by the reduced response to a second injection. Flinching from the second injection was 20% +/- 5%, 57% +/- 18%, 79% +/- 35%, and 100% +/- 17% of that from the first injection (both 200 micromol/L, 2 nmol) at respective intervals of 24, 30, 48, and 72 h. Inhibition of afferent impulses by local anesthesia of the sciatic nerve, reducing initial flinching to 6%-13% of control, did not affect the tachyphylaxis for the second injection at 24 h. There was no cross-desensitization between formalin and ET-1 injected sequentially into the same paw. Suppression of descending inhibitory effects from endogenous opiates by naloxone (5-8 mg/kg, i.p.), given 30 min before the second ET-1 injection, did not prevent tachyphylaxis. Diffuse effects caused by an initial subcutaneous ET-1 injection into the tail or forepaw resulted in sensitization of the response to ET-1 in the hind paw, rather than tachyphylaxis. In contrast, selective inhibition of local ETA receptors during the initial administration of ET-1, by the antagonist BQ-123 (3.2 mmol/L), reduced tachyphylaxis of nocifensive fli...Continue Reading

References

Jan 1, 1993·Journal of Cardiovascular Pharmacology·C Cyr, R M Kris
Apr 1, 1995·Anesthesiology·J G ThalhammerG R Strichartz
Mar 1, 1993·The American Journal of Physiology·R MarsaultC Frelin
Mar 1, 1996·Pain·T J BrennanG F Gebhart
Apr 5, 2000·The Journal of Biological Chemistry·T BremnesH Attramadal
May 31, 2001·The Journal of Biological Chemistry·J D PaascheH Attramadal
May 22, 2003·Pharmacology, Biochemistry, and Behavior·Tsukasa SakuradaShinobu Sakurada
Dec 30, 2008·The Journal of Pain : Official Journal of the American Pain Society·Alla KhodorovaGary Strichartz
Jun 30, 2009·The Journal of Pain : Official Journal of the American Pain Society·Alla KhodorovaGary Strichartz

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Citations

Nov 26, 2015·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Elodie SchaefferAurélie Birenbaum
Mar 1, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Travis P BarrGary R Strichartz

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