TY - JOUR
T1 - Choline attenuates inflammatory hyperalgesia activating nitric oxide/cGMP/ATP-sensitive potassium channels pathway
AU - Kusuda, Ricardo
AU - Carreira, Eleonora Uchôa
AU - Ulloa, Luis
AU - Cunha, Fernando Queiroz
AU - Kanashiro, Alexandre
AU - Cunha, Thiago Mattar
N1 - Funding Information:
FQC and TMC designed the study. RK and EUC performed the mouse experiments. RK, LU, AK, and TMC wrote the manuscript. RK and AK prepared the figures. AK and TMC edited the manuscript. FQC and TMC provided financial support.
Funding Information:
The research leading to these results has received funding from S?o Paulo Research Foundation (FAPESP; grants 13/08216-2, 12/23846-0, 11/20343-4, and 10/16823-8) and from National Council for Scientific and Technological Development (CNPq; 118636/2017-0).
PY - 2020/1/15
Y1 - 2020/1/15
N2 - 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), and glibenclamide (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.
AB - 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), and glibenclamide (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.
KW - Alpha 7-nicotinic acetylcholine receptor
KW - Choline
KW - Hyperalgesia
KW - Inflammation
KW - Neuroimmunomodulation
UR - http://www.scopus.com/inward/record.url?scp=85076551338&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076551338&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2019.146567
DO - 10.1016/j.brainres.2019.146567
M3 - Article
C2 - 31783002
AN - SCOPUS:85076551338
VL - 1727
JO - Brain Research
JF - Brain Research
SN - 0006-8993
M1 - 146567
ER -