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Choline attenuates inflammatory hyperalgesia activating nitric oxide/cGMP/ATP-sensitive potassium channels pathway.

Abstract
New findings on neural regulation of immunity are allowing the design of novel pharmacological strategies to control inflammation and nociception. Herein, we report that choline, a 7-nicotinic acetylcholine receptor (α7nAChRs) agonist, prevents carrageenan-induced hyperalgesia without affecting inflammatory parameters (neutrophil migration or cytokine/chemokines production) or inducing sedation or even motor impairment. Choline also attenuates prostaglandin-E2 (PGE2)-induced hyperalgesia via α7nAChR activation and this antinociceptive effect was abrogated by administration of LNMMA (a nitric oxide synthase inhibitor), ODQ (an inhibitor of soluble guanylate cyclase; cGMP), andglibenclamide(an inhibitor of ATP-sensitive potassium channels). Furthermore, choline attenuates long-lasting Complete Freund's Adjuvant and incision-induced hyperalgesia suggesting its therapeutic potential to treat pain in rheumatoid arthritis or post-operative recovery, respectively. Our results suggest that choline modulates inflammatory hyperalgesia by activating the nitric oxide/cGMP/ATP-sensitive potassium channels without interfering in inflammatory events, and could be used in persistent pain conditions.
AuthorsRicardo Kusuda, Eleonora Uchôa Carreira, Luis Ulloa, Fernando Queiroz Cunha, Alexandre Kanashiro, Thiago Mattar Cunha
JournalBrain research (Brain Res) Vol. 1727 Pg. 146567 (01 15 2020) ISSN: 1872-6240 [Electronic] Netherlands
PMID31783002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2019 Elsevier B.V. All rights reserved.
Chemical References
  • KATP Channels
  • alpha7 Nicotinic Acetylcholine Receptor
  • Nitric Oxide
  • Freund's Adjuvant
  • Cyclic GMP
  • Dinoprostone
  • Choline
Topics
  • Animals
  • Choline (pharmacology, therapeutic use)
  • Cyclic GMP (metabolism)
  • Dinoprostone (metabolism)
  • Freund's Adjuvant
  • Hyperalgesia (drug therapy)
  • Inflammation (drug therapy)
  • KATP Channels (metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide (metabolism)
  • alpha7 Nicotinic Acetylcholine Receptor (agonists)

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