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Interaction of IL-1β and P2X(3) receptor in pathologic masseter muscle pain

N Noma1, M Shinoda, K Honda

  • 1Department of Oral Diagnostic Sciences, Nihon University School of Dentistry, Tokyo, Japan. noma.noboru@nihon-u.ac.jp

Insights

Chronic masseter muscle pain may involve P2X3 receptor (P2X3R) expression. This study found increased P2X3R, IL-1β, and ATP release in rats after muscle contraction, suggesting a role in pain.

Area of Science:

  • Neuroscience
  • Pain Research
  • Muscle Physiology

Background:

  • Chronic masseter muscle pain is a common temporomandibular disorder symptom.
  • The precise mechanisms driving this pain, particularly mechanical hyperalgesia, are not fully understood.
  • P2X3 receptor (P2X3R) involvement in muscle pain warrants investigation.

Purpose of the Study:

  • To investigate the role of P2X3 receptor (P2X3R) expression in mechanical hyperalgesia following masseter muscle contraction (CMM).
  • To examine the relationship between P2X3R, Interleukin-1 beta (IL-1β), and Adenosine Triphosphate (ATP) release in masseter muscle pain.
  • To assess the therapeutic potential of P2X3R antagonists in alleviating CMM-induced pain.

Main Methods:

  • Induction of CMM in a rat model.
  • Measurement of head-withdrawal threshold (HWT) to mechanical stimulation.
  • Quantification of IL-1β levels in masseter muscle.
  • Assessment of P2X3R-positive neurons in the trigeminal ganglion (TG).
  • Evaluation of ATP release from masseter muscle.
  • Administration of IL-1β receptor antagonist and P2X3/2/3 receptor antagonist (A-317491).

Main Results:

  • CMM rats exhibited significantly lower HWT and higher IL-1β levels in masseter muscle compared to controls.
  • Increased P2X3R-positive neurons were observed in the TG of CMM rats, correlating with IL-1β injections.
  • IL-1β receptor antagonist administration attenuated P2X3R upregulation.
  • ATP release from masseter muscle was significantly enhanced after CMM.
  • Administration of P2X3/2/3 receptor antagonist A-317491 attenuated the decrease in HWT in CMM rats.

Conclusions:

  • P2X3R expression, alongside elevated IL-1β and ATP release in the masseter muscle, plays a significant role in mechanical hyperalgesia after excessive muscle contraction.
  • Targeting P2X3R presents a potential therapeutic strategy for managing masseter muscle pain associated with temporomandibular disorders.