Abstract
We have previously shown that the male sex steroid testosterone inhibits slightly, but the female sex steroid 17β-estradiol (E2) potentiates dramatically, the capsaicin receptor-mediated current in rat dorsal root ganglion (DRG) neurons. Here, we used pharmacological methods and the nociceptive behavioral test to determine whether there is a sex difference in capsaicin-induced acute pain in rats in vivo and what mechanism underlies this sex difference. Results revealed that intradermal injection of capsaicin induced a dose-dependent nocifensive response in males and females, with the dose required to produce a comparable level of nociception being approximately 3- to 4-fold higher in males than in females. In addition, females during the proestrus stage exhibited significantly greater capsaicin-induced nocifensive responses compared with the estrus stage. Moreover, the female's enhanced sensitivity to the capsaicin-induced nocifensive response was completely reversed by ovariectomy 6 weeks before capsaicin injection. It is noteworthy that intradermal coinjection of E2 but not progesterone with capsaicin potentiated the capsaicin-induced nocifensive response in ovariectomized rats. Likewise, intradermal E2 injection dose-dependently potentiated the capsaicin-induced nocifensive response in male rats. Furthermore, potentiation by E2 of the capsaicin-induced nocifensive response in male rats was not significantly reduced by a selective protein kinase C (PKC) inhibitor or by a selective protein kinase A (PKA) inhibitor, indicating that neither PKC nor PKA was involved in the effect of E2. These data demonstrate that E2 mediates the female's enhanced sensitivity to capsaicin-induced acute pain, consistent with potentiation by E2 of the capsaicin receptor-mediated current in rat DRG neurons.
Footnotes
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This work was supported by the National Science Council of Taiwan [Grants NSC 94-2320-B-006-055, NSC 95-2320-B-006-051-MY2].
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.109.158402
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ABBREVIATIONS:
- DRG
- dorsal root ganglion
- E2
- 17β-estradiol
- PKC
- protein kinase C
- PKA
- protein kinase A
- TRPV1
- transient receptor potential vanilloid subtype 1
- OVX
- ovariectomy
- DMSO
- dimethyl sulfoxide
- Bis I
- bisindolylmaleimide I
- ANOVA
- analysis of variance
- ER
- estrogen receptor
- H89
- N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline sulfonamide
- Veh
- vehicle.
- Received July 2, 2009.
- Accepted September 21, 2009.
- © 2009 by The American Society for Pharmacology and Experimental Therapeutics
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