TRPV1 and TRPV4 play pivotal roles in delayed onset muscle soreness.

Abstract

Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes tenderness and movement related pain after some delay (delayed-onset muscle soreness, DOMS). We previously demonstrated that nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) are up-regulated in exercised muscle through up-regulation of cyclooxygenase (COX)-2, and they sensitized nociceptors resulting in mechanical hyperalgesia. There is also a study showing that transient receptor potential (TRP) ion channels are involved in DOMS. Here we examined whether and how TRPV1 and/or TRPV4 are involved in DOMS. We firstly evaluated a method to measure the mechanical withdrawal threshold of the deep tissues in wild-type (WT) mice with a modified Randall-Selitto apparatus. WT, TRPV1-/- and TRPV4-/- mice were then subjected to LC. Another group of mice received injection of murine NGF-2.5S or GDNF to the lateral gastrocnemius (LGC) muscle. Before and after these treatments the mechanical withdrawal threshold of LGC was evaluated. The change in expression of NGF, GDNF and COX-2 mRNA in the muscle was examined using real-time RT-PCR. In WT mice, mechanical hyperalgesia was observed 6-24 h after LC and 1-24 h after NGF and GDNF injection. LC induced mechanical hyperalgesia neither in TRPV1-/- nor in TRPV4-/- mice. NGF injection induced mechanical hyperalgesia in WT and TRPV4-/- mice but not in TRPV1-/- mice. GDNF injection induced mechanical hyperalgesia in WT but neither in TRPV1-/- nor in TRPV4-/- mice. Expression of NGF and COX-2 mRNA was significantly increased 3 h after LC in all genotypes. However, GDNF mRNA did not increase in TRPV4-/- mice. These results suggest that TRPV1 contributes to DOMS downstream (possibly at nociceptors) of NGF and GDNF, while TRPV4 is located downstream of GDNF and possibly also in the process of GDNF up-regulation.

• Authors: Hiroki Ota, Kimiaki Katanosaka, Shiori Murase, Makiko Kashio, Makoto Tominaga, Kazue Mizumura
• Journal: PloS one (PLoS One) Vol. 8 Issue 6 Pg. e65751 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23799042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glial Cell Line-Derived Neurotrophic Factor
• RNA, Messenger
• TRPV Cation Channels
• TRPV1 protein, mouse
• Trpv4 protein, mouse
• Nerve Growth Factor

Topics

• Animals
• Glial Cell Line-Derived Neurotrophic Factor (genetics, physiology)
• Hyperalgesia (physiopathology)
• Mice
• Mice, Knockout
• Muscle Contraction (physiology)
• Myalgia (physiopathology)
• Nerve Growth Factor (genetics)
• Physical Conditioning, Animal
• RNA, Messenger (genetics)
• TRPV Cation Channels (physiology)
• Up-Regulation