Contribution of alpha(2) receptor subtypes to nerve injury-induced pain and its regulation by dexmedetomidine

British Journal of Pharmacology
A B MalmbergA I Basbaum

Abstract

There is evidence that noradrenaline contributes to the development and maintenance of neuropathic pain produced by trauma to a peripheral nerve. It is, however, unclear which subtype(s) of alpha adrenergic receptors (AR) may be involved. In addition to pro-nociceptive actions of AR stimulation, alpha(2) AR agonists produce antinociceptive effects. Here we studied the contribution of the alpha(2) AR subtypes, alpha(2A), alpha(2B) and alpha(2C) to the development of neuropathic pain. We also examined the antinociceptive effect produced by the alpha(2) AR agonist dexmedetomidine in nerve-injured mice. The studies were performed in mice that carry either a point (alpha(2A)) or a null (alpha(2B) and alpha(2C)) mutation in the gene encoding the alpha(2) AR. To induce a neuropathic pain condition, we partially ligated the sciatic nerve and measured changes in thermal and mechanical sensitivity. Baseline mechanical and thermal withdrawal thresholds were similar in all mutant and wild-type mice; and, after peripheral nerve injury, all mice developed comparable hypersensitivity (allodynia) to thermal and mechanical stimulation. Dexmedetomidine reversed the allodynia at a low dose (3 microg kg(-1), s.c.) and produced antinociceptive effe...Continue Reading

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Citations

Feb 6, 2004·European Journal of Pharmacology·Umit Kazim OzdoğanMika Scheinin
Jan 20, 2004·Pharmacology & Therapeutics·Melanie Philipp, Lutz Hein
May 20, 2003·European Journal of Pharmacology·Janne LähdesmäkiHeikki Mansikka
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Feb 13, 2018·Frontiers in Neural Circuits·Xiao YuWilliam Wisden
Jan 19, 2019·British Journal of Pharmacology·Zahra Bahari, Gholam Hossein Meftahi
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