ASICs are Required for Immediate Exercise-Induced Muscle Pain (IEIP), but not Delayed Onset Muscle Soreness (DOMS)

Abstract

IEIP and DOMS are two types of muscle pain induced by exercise. IEIP occurs during whereas DOMS appears days after exercise. Acid sensing ion channels (ASICs) expressed in muscle afferents, play a role in different pain conditions. ASICs are regulated via chemicals released during intense muscle contraction and microinjuries. Recently, we showed that ASICs are required for IEIP. Here, we tested if ASICs are also required for DOMS. Wild type (WT) and ASIC3-/- mice were divided into control and exercise groups. Exercise group underwent an exhaustive exercise; control group were placed on a non-moving treadmill. Locomotor movement was measured via Open field test to examine fatigue and/or soreness immediately and 24h after exercise. Next, exercise-induced muscle pain was assessed by muscle withdrawal threshold (MWT) at baseline, immediately and 24h after exercise. Our results showed; ASIC3-/- had similar baseline locomotor activity, muscle pain responses and exercise performance as WT. However, ASIC3-/- showed different responses after exercise compared to WT. WT had a lower MWT immediately and 24h after exercise compared to baseline. On the other hand, ASIC3-/- showed a lower MWT only 24h after exercise, but not immediately after. In addition, ASIC3-/- had significant lower locomotor activity than WT immediately after exercise. Also, ASIC3-/- had significant lower movement 24h after exercise compared to control ASIC3-/-, however this difference was not significant for WT mice. In summary, while WT and ASIC3-/- had a same exercise performance, they had different pain perception and fatigue immediately, but not 24h after exercise. Unlike WT, ASIC3-/- did not develop IEIP, even though ASIC3-/- had a higher fatigue level than WT as measured by diminished locomotion after exercise. On the other hand, ASIC3-/- developed DOMS a day after exercise like WT. These results show ASICs are required for immediate exercise-induced pain, but not exercise-induced fatigue and DOMS. Supported by the Department of Veterans Affairs Merit Award (5I01BX000776).