Premium
EP 2 receptor plays pivotal roles in generating mechanical hyperalgesia after lengthening contractions
Author(s) -
Ota H.,
Katanosaka K.,
Murase S.,
Furuyashiki T.,
Narumiya S.,
Mizumura K.
Publication year - 2018
Publication title -
scandinavian journal of medicine and science in sports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.575
H-Index - 115
eISSN - 1600-0838
pISSN - 0905-7188
DOI - 10.1111/sms.12954
Subject(s) - glial cell line derived neurotrophic factor , downregulation and upregulation , hyperalgesia , endocrinology , prostaglandin e2 receptor , medicine , receptor , agonist , prostaglandin e2 , neurotrophic factors , nerve growth factor , chemistry , cyclooxygenase , bradykinin , prostaglandin , nociception , biochemistry , enzyme , gene
We previously demonstrated that nerve growth factor ( NGF ) and glial cell line‐derived neurotrophic factor ( GDNF ) were upregulated after lengthening contractions ( LC ) in exercised muscle through B2 bradykinin receptor activation and cyclooxygenase ( COX )‐2 upregulation, respectively, and that these trophic factors sensitized nociceptors resulting in mechanical hyperalgesia (delayed‐onset muscle soreness, DOMS ). Here, we examined the prostaglandin receptor subtype involved in DOMS . The mechanical withdrawal threshold of the exercised muscle was measured before and after LC in rats administered prostaglandin E 2 receptor ( EP ) antagonists before LC , or in wild‐type ( WT ), EP 2 knockout ( EP 2 −/− ), and IP knockout ( IP −/− ) mice. The change in expression of NGF , GDNF , or COX ‐2 mRNA was examined using real‐time RT ‐ PCR in the muscle in EP 2 −/− and WT mice. None of the antagonists to EP 1, EP 3, and EP 4 receptors ( ONO ‐8713, ONO ‐ AE 5‐599, and ONO ‐ AE 3‐208, respectively) induced a significant difference in DOMS compared with controls in rats. WT and IP −/− mice developed mechanical hyperalgesia after LC , but EP 2 −/− mice did not. Upregulation of NGF , GDNF , and COX ‐2 mRNA was observed after LC in WT mice but not in EP 2 −/− mice. Injecting an EP 2 agonist ( ONO ‐ AE 1‐259‐01) into the mouse muscle increased expression of COX ‐2 mRNA . These results suggest that EP 2 contributes to generating mechanical hyperalgesia through positive feedback upregulation of COX ‐2 expression in muscle after LC.