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Roles of ASIC3, TRPV1, and Na V 1.8 in the Transition from Acute to Chronic Pain in a Mouse Model of Fibromyalgia

2014; SAGE Publishing; Volume: 10; Linguagem: Inglês

10.1186/1744-8069-10-40

1744-8069

Wei-Nan Chen, Cheng‐Han Lee, Shing-Hong Lin, Chia-Wen Wong, Wei‐Hsin Sun, John N. Wood, Chih‐Cheng Chen,

Thermoregulation and physiological responses

Background: 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. Results: 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). Activation of ASIC3 was associated with increased activity of tetrodotoxin (TTX)-sensitive voltage-gated sodium channels but not protein kinase Cε (PKCε) in isolectin B4 (IB4)-negative muscle nociceptors. In contrast, increased activity of TTX-resistant voltage-gated sodium channels with ASIC3 or TRPV1 activation in Na V 1.8-positive muscle nociceptors was required for the development of chronic hyperalgesia. Accordingly, compared to wild type mice, Na V 1.8-null mice showed briefer acid-induced hyperalgesia (5 days vs. >27 days). Conclusion: 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 Na V 1.8 activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain.