Upregulated glial cell line-derived neurotrophic factor through cyclooxygenase-2 activation in the muscle is required for mechanical hyperalgesia after exercise in rats.

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Upregulated glial cell line-derived neurotrophic factor through cyclooxygenase-2 activation in the muscle is required for mechanical hyperalgesia after exercise in rats.

J Physiol. 2013 Apr 15;

Authors: Murase S, Terazawa E, Hirate K, Yamanaka H, Kanda H, Noguchi K, Ota H, Queme F, Taguchi T, Mizumura K

Abstract
Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes delayed onset muscle soreness (DOMS), a kind of muscular mechanical hyperalgesia. Previously we reported that bradykinin-like substance released from the muscle during exercise plays a pivotal role in triggering the process of muscular mechanical hyperalgesia by upregulating nerve growth factor (NGF) in exercised muscle of rats. We show here that cyclooxygenase (COX)-2 and glial cell line-derived neurotrophic factor (GDNF) are also involved in DOMS. COX-2 inhibitors but not COX-1 inhibitors given orally before LC completely suppressed the development of DOMS, but when given 2 days after LC they failed to reverse the mechanical hyperalgesia. COX-2 mRNA and protein in exercised muscle increased 6-13 fold in mRNA and 1.7-2 fold in protein 0-12 hours after LC. COX-2 inhibitors did not suppress NGF upregulation after LC. Instead, we found GDNF mRNA was upregulated 7-8 fold in the exercised muscle 12 hours to 1 day after LC and blocked by pretreatment of COX-2 inhibitors. In situ hybridization studies revealed that both COX-2 and GDNF mRNA signals increased at the periphery of skeletal muscle cells 12 hours after LC. The accumulation of COX-2 mRNA signals was also observed in small blood vessels. Intramuscular injection of anti-GDNF antibody 2 days after LC partly reversed DOMS. Based on these findings, we conclude that GDNF upregulation through COX-2 activation is essential to mechanical hyperalgesia after exercise.

PMID: 23587883 [PubMed - as supplied by publisher]

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