title: Bradykinin and nerve growth factor play pivotal roles in muscular mechanical hyperalgesia after exercise (delayed-onset muscle soreness).
abstract: Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes delayed-onset muscle soreness (DOMS), a kind of muscular mechanical hyperalgesia. The substances that induce this phenomenon are largely unknown. Peculiarly, DOMS is not perceived during and shortly after exercise, but rather is first perceived after approximately 1 d. Using B(2) bradykinin receptor antagonist HOE 140, we show here that bradykinin released during exercise plays a pivotal role in triggering the process that leads to muscular mechanical hyperalgesia. HOE 140 completely suppressed the development of muscular mechanical hyperalgesia when injected before LC, but when injected 2 d after LC failed to reverse mechanical hyperalgesia that had already developed. B(1) antagonist was ineffective, regardless of the timing of its injection. Upregulation of nerve growth factor (NGF) mRNA and protein occurred in exercised muscle over a comparable time course (12 h to 2 d after LC) for muscle mechanical hyperalgesia. Antibodies to NGF injected intramuscularly 2 d after exercise reversed muscle mechanical hyperalgesia. HOE 140 inhibited the upregulation of NGF. In contrast, shortening contraction or stretching induced neither mechanical hyperalgesia nor NGF upregulation. Bradykinin together with shortening contraction, but not bradykinin alone, reproduced lasting mechanical hyperalgesia. We also showed that rat NGF sensitized thin-fiber afferents to mechanical stimulation in the periphery after 10-20 min. Thus, NGF upregulation through activation of B(2) bradykinin receptors is essential (though not satisfactory) to mechanical hyperalgesia after exercise. The present observations explain why DOMS occurs with a delay, and why lengthening contraction but not shortening contraction induces DOMS.
authors.affiliation: Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Murase
authors.forename: Etsuji
authors.initials: E
authors.lastname: Terazawa
authors.forename: Fernando
authors.initials: F
authors.lastname: Queme
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ota
authors.forename: Teru
authors.initials: T
authors.lastname: Matsuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirate
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kozaki
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Katanosaka
authors.forename: Toru
authors.initials: T
authors.lastname: Taguchi
authors.forename: Hisako
authors.initials: H
authors.lastname: Urai
authors.forename: Kazue
authors.initials: K
authors.lastname: Mizumura
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D010147:Pain Measurement / Q000379:methods; D010805:Physical Conditioning, Animal / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D001920:Bradykinin