Abstract
Fibromyalgia (FM) is among the most common chronic pain syndromes encountered in clinical practice, but there is limited understanding of FM pathogenesis. We examined the contribution of transient receptor potential vanilloid 1 (TRPV1) and TRPV4 channels to chronic pain in the repeated acid injection mouse model of FM and the potential therapeutic efficacy of electroacupuncture. Electroacupuncture (EA) at the bilateral Zusanli (ST36) acupoint reduced the long-lasting mechanical hyperalgesia induced by repeated acid saline (pH 4) injection in mouse hindpaw. Isolated L5 dorsal root ganglion (DRG) neurons from FM model mice (FM group) were hyperexcitable, an effect reversed by EA pretreatment (FM + EA group). The increase in mechanical hyperalgesia was also accompanied by upregulation of TRPV1 expression and phosphoactivation of extracellular signal regulated kinase (pERK) in the DRG, whereas DRG expression levels of TRPV4, p-p38, and p-JNK were unaltered. Blockade of TRPV1, which was achieved using TRPV1 knockout mice or via antagonist injection, and pERK suppressed development of FM-like pain. Both TRPV1 and TRPV4 protein expression levels were increased in the spinal cord (SC) of model mice, and EA at the ST36 acupoint decreased overexpression. This study strongly suggests that DRG TRPV1 overexpression and pERK signaling, as well as SC TRPV1 and TRPV4 overexpression, mediate hyperalgesia in a mouse FM pain model. The therapeutic efficacy of EA may result from the reversal of these changes in pain transmission pathways.
Highlights
Activation of acid-sensitive ion channels may contribute to the pain of fibromyalgia (FM) [1,2,3,4]
The contributions of transient receptor potential vanilloid 1 (TRPV1) and TRPV4 channel activity have been well documented in several pain models [30,31]
Inhibition or underexpression of TRPV1 and TRPV4 generally results in antinociceptive effects in animal models, but the role of these channels in FM is still unclear [14,20]
Summary
Activation of acid-sensitive ion channels may contribute to the pain of fibromyalgia (FM) [1,2,3,4]. Acidosis from lactate accumulation is a common trigger for muscle pain [5,6]; FM is strongly associated with acid-sensing ion channel 3 (ASIC3) [4]. Repeated acid injection can PLOS ONE | DOI:10.1371/journal.pone.0128037. TRPV1 Involved in Acupuncture Analgesia in Mice Fibromyalgia Repeated acid injection can PLOS ONE | DOI:10.1371/journal.pone.0128037 June 4, 2015
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