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Estrogen modulation of peripheral pain signal transduction: involvement of P2X(3) receptors

Bei Ma1, Li-Hua Yu, Juan Fan

  • 1Department of Physiology, Shanghai Second Military Medical University, Shanghai, 200433, People's Republic of China, mabei08@yahoo.com.cn.

Purinergic Signalling
|April 13, 2011
PubMed

Insights

Estrogen reduces pain sensitivity by modulating P2X(3) receptors in the dorsal root ganglion (DRG). This study shows estrogen decreases P2X(3) receptor expression, alleviating mechanical hyperalgesia in female rats.

Area of Science:

  • Neuroscience
  • Pain Research
  • Endocrinology

Background:

  • Gonadal hormones influence pain perception, but mechanisms are unclear.
  • Adenosine triphosphate (ATP) receptor subunit P2X(3) is implicated in pain signaling.
  • Estrogen's role in peripheral pain modulation requires further investigation.

Purpose of the Study:

  • To determine if P2X(3) receptors mediate estrogen's modulatory effects on peripheral pain in dorsal root ganglion (DRG).
  • To investigate the impact of ovariectomy and estradiol replacement on pain behavior and P2X(3) receptor expression in rats.
  • To examine the effect of estrogen on P2X(3) mRNA and protein levels in cultured DRG neurons.

Main Methods:

  • Mechanical pain behavior tests in sham, ovariectomized (OVX), and estradiol-replaced (OVX+E(2)) rats.
  • Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) for P2X(3) mRNA levels.
  • Western blot analysis for P2X(3) protein concentrations.
  • Pharmacological inhibition of P2X(3)/P2X(2/3) receptors using TNP-ATP and A-317491.
  • In vitro studies with cultured DRG neurons treated with 17β-estradiol and ICI 182,780.

Main Results:

  • Ovariectomy induced mechanical hyperalgesia in rats, which was reversed by estradiol replacement.
  • P2X(3) receptor mRNA and protein levels were significantly elevated in OVX rats and normalized after estradiol treatment.
  • P2X(3) receptor antagonists (TNP-ATP, A-317491) reversed hyperalgesia in OVX rats.
  • 17β-estradiol decreased P2X(3) mRNA in cultured DRG neurons in a concentration-dependent manner, an effect blocked by an estrogen receptor antagonist.

Conclusions:

  • Female gonadal hormone 17β-estradiol modulates peripheral pain signaling by downregulating P2X(3) receptor expression and function in primary sensory neurons.
  • Estrogen likely exerts its analgesic effects through genomic mechanisms involving estrogen receptors.
  • P2X(3) receptors represent a potential therapeutic target for managing pain conditions influenced by gonadal hormone status.

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