ASICs are required for immediate exercise‐induced muscle pain (IEIP), but not delayed‐onset muscle soreness (DOMS)

Abstract

Introduction IEIP and DOMS are types of muscle pain induced by exercise. IEIP occurs during and immediately after, whereas DOMS occurs days after exercise, and are attributed to metabolites and inflammation in muscle, respectively. Acid sensing ion channels (ASICs), H+-gated channels expressed in muscle afferents, play a role in different pain conditions. ASICs are activated by H+ and other chemicals released during intense muscle contraction and microinjuries. Recently, we showed that ASICs are required for IEIP. PURPOSE Here, we tested if ASICs are also required for DOMS. METHODS C57BL/6 wild type (WT) and ASIC3-/- mice underwent an exhaustive exercise (exercise groups), or were placed on a non-moving treadmill for a same amount of time (control groups). Exercise-induced muscle pain was assessed by muscle withdrawal threshold (MWT) at baseline, immediately and 24h after exercise. Locomotor movement, grip strength and exercise performance were tested at baseline and 24hrs after exercise for WT and ASIC3-/- to evaluate DOMS. RESULTS ASIC3-/- had similar baseline muscle pain, locomotor activity, grip strength, and exercise performance as WT mice. WT showed diminished MWT immediately after exercise indicated they developed IEIP (P < 0.001), but ASIC3-/- mice did not. However, both, ASIC3-/- and WT had similarly lower MWT (P < 0.05) and grip strength (P < 0.01) 24hrs after baseline-exercise. On the other hand, ASIC3-/- displayed significantly lower locomotor activity and repeat exercise performance at 24h timepoint compared to WT mice­ (P < 0.05). CONCLUSION While WT and ASIC3-/- had a same exercise performance, they had different pain perception immediately after, but not a day after exercise. Unlike WT mice, ASIC3-/- did not develop IEIP. At 24h after exercise, ASIC3-/- developed similar DOMS features (hyperalgesia and lower strength) as WT mice. Interestingly, ASIC3 -/- mice had diminished locomotor movement and repeat exercise performance at 24h. These results show ASICs are required for IEIP, but not DOMS, and they might play a protective role from muscle injury during metabolic perturbations like high intensity exercise.