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.