Activation of TRPV1 and TRPA1 leads to muscle nociception and mechanical hyperalgesia

Pain. 2009 Aug;144(3):270-277. doi: 10.1016/j.pain.2009.04.021. Epub 2009 May 22.


The involvement of TRPV1 and TRPA1 in mediating craniofacial muscle nociception and mechanical hyperalgesia was investigated in male Sprague-Dawley rats. First, we confirmed the expression of TRPV1 in masseter afferents in rat trigeminal ganglia (TG), and provided new data that TRPA1 is also expressed in primary afferents innervating masticatory muscles in double-labeling immunohistochemistry experiments. We then examined whether the activation of each TRP channel in the masseter muscle evokes acute nocifensive responses and leads to the development of masseter hypersensitivity to mechanical stimulation using the behavioral models that have been specifically designed and validated for the craniofacial system. Intramuscular injections with specific agonists for TRPV1 and TRPA1, capsaicin and mustard oil (MO), respectively, produced immediate nocifensive hindpaw responses followed by prolonged mechanical hyperalgesia in a concentration-dependent manner. Pretreatment of the muscle with a TRPV1 antagonist, capsazepine, effectively attenuated the capsaicin-induced muscle nociception and mechanical hyperalgesia. Similarly, pretreatment of the muscle with a selective TRPA1 antagonist, AP18, significantly blocked the MO-induced muscle nociception and mechanical hyperalgesia. We confirmed these data with another set of selective antagonist for TRPV1 and TRPA1, AMG9810 and HC030031, respectively. Collectively, these results provide compelling evidence that TRPV1 and TRPA1 can functionally contribute to muscle nociception and hyperalgesia, and suggest that TRP channels expressed in muscle afferents can engage in the development of pathologic muscle pain conditions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acrylamides / pharmacology
  • Afferent Pathways / drug effects
  • Afferent Pathways / metabolism
  • Animals
  • Ankyrins
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Facial Pain / metabolism*
  • Facial Pain / physiopathology
  • Hyperalgesia / metabolism*
  • Hyperalgesia / physiopathology
  • Injections, Intramuscular
  • Male
  • Masticatory Muscles / innervation*
  • Masticatory Muscles / physiopathology
  • Mustard Plant
  • Nociceptors / drug effects
  • Nociceptors / metabolism*
  • Pain Measurement / methods
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Plant Oils / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism
  • Sensory System Agents / pharmacology
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TRPV Cation Channels / drug effects
  • TRPV Cation Channels / metabolism*
  • Trigeminal Ganglion / drug effects
  • Trigeminal Ganglion / metabolism


  • 3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide
  • Acrylamides
  • Ankyrins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Calcium Channels
  • Plant Oils
  • Sensory System Agents
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TRPV Cation Channels
  • Trpa1 protein, rat
  • Trpv1 protein, rat
  • capsazepine
  • Capsaicin
  • mustard oil