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Tissue acidosis is effective in causing chronic muscle pain. However, how muscle nociceptors contribute to the transition from acute to chronic pain is largely unknown.
Here we showed that a single intramuscular acid injection induced a priming effect on muscle nociceptors of mice. The primed muscle nociceptors were plastic and permitted the development of long-lasting chronic hyperalgesia induced by a second acid insult.
The plastic changes of muscle nociceptors were modality-specific and required the activation of acid-sensing ion channel 3 (ASIC3) or transient receptor potential cation channel V1 (TRPV1).
increased activity of TTX-resistant voltage-gated sodium channels with ASIC3 or TRPV1 activation in NaV1.8-positive muscle nociceptors was required for the development of chronic hyperalgesia.
ASIC3 activation may manifest a new type of nociceptor priming in IB4-negative muscle nociceptors. The activation of ASIC3 and TRPV1 as well as enhanced NaV1.8 activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain.
Although both peripheral and central sensitizations are believed involved in the transition from acute to chronic muscle pain, the underlying mechanism is not well understood
An emerging hypothesis of hyperalgesic priming proposed by Jon Levine is that the transition might involve neural plasticity in primary afferent nociceptors, whereby an acute noxious stimulation can trigger long-lasting hypersensitivity of nociceptors to subsequent insults
Tissue acidosis in muscles related to ischemia and inflammation has a profound effect on the initiation and development of chronic muscle pain
Proton-sensing ion channels, such as acid-sensing ion channel 3 (ASIC3) and transient receptor potential cation channel V1 (TRPV1), are involved in activating muscle nociceptors and inducing the central sensitization that occurs in animal models of chronic muscle pain