Fig. 2.

Soreness hypothesis. Tissue acidosis simultaneously evokes a pro-nociceptive signaling via ASIC3/TRPV1 activation and an anti-nociception via non-ASIC3, non-TRPV1 acid signaling. In most cases, pain associated with tissue acidosis is the balanced result of pro-nociceptive and anti-nociceptive acid signaling. In physical therapy, soreness sensation induced by acupuncture and/or noxipoint therapy is a sign of successful analgesia to balance the pro-nociceptive signaling. Fibromyalgia patients might have soreness phenotypes due to an imbalance of acid signaling in muscle nociceptors, especially with impaired non-ASIC3, non-TRPV1 acid signaling