Editors' ChoicePhysiology

Building Muscle Is a Pain

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Science Signaling  16 Mar 2010:
Vol. 3, Issue 113, pp. ec83
DOI: 10.1126/scisignal.3113ec83

People who engage in unaccustomed exercise are likely to feel delayed-onset muscle soreness, which occurs 1 to 2 days later and resolves after 3 to 7 days. Because bradykinin is released from muscle during exercise and is known to mediate pain, Murase et al. examined the role of bradykinin in a rat model of mechanical muscle hyperalgesia. Pharmacological block of bradykinin 2 receptors before lengthening-contraction (LC) exercise of the rat leg muscle prevented the development of mechanical hyperalgesia, but application 30 minutes after LC exercise (before hyperalgesia onset) was not effective at preventing the development of hyperalgesia, and application during the time of the hyperalgesic response (2 days after LC) failed to reverse the hyperalgesia. Transcript and protein abundance of nerve growth factor (NGF) was increased in muscle after LC exercise but not after other exercise paradigms that fail to produce hyperalgesia. Intramuscular injection of antibodies that block NGF activity 6 hours after LC exercise blocked generation of muscle hyperalgesia, and injection of high concentrations during the period of hyperalgesia partially reversed the hyperalgesia. Injection of NGF into the muscle induced mechanical hyperalgesia in the absence of exercise. Unexpectedly, injection of bradykinin failed to stimulate hyperalgesia in the absence of exercise. However, the bradykinin 2 receptor antagonist at concentrations that blocked hyperalgesia prevented the increase in NGF associated with exercise, suggesting that the bradykinin-induced hyperalgesia involved stimulation of NGF production. Finally, intramuscular injection of NGF in an isolated muscle-nerve preparation resulted in increased afferent nerve activity in response to mechanical stimulation. Thus, exercise that induces the production of bradykinin triggers a pathway that induces NGF, which sensitizes pain nerves associated with muscles, which contributes to delayed-onset muscle soreness.

S. Murase, E. Terazawa, F. Queme, H. Ota, T. Matsuda, K. Hirate, Y. Kozaki, K. Katanosaka, T. Taguchi, H. Urai, K. Mizumura, Bradykinin and nerve growth factor play pivotal roles in muscular mechanical hyperalgesia after exercise (delayed-onset muscle soreness). J. Neurosci. 30, 3752–3761 (2010). [Abstract] [Full Text]