Abstract
Many studies have demonstrated that premenopausal women are at increased risk for various pain disorders. Pain-sensing neurons, termed “nociceptors,” in the trigeminal ganglia (TG) and dorsal root ganglia (DRG) express receptors for inflammatory mediators and noxious physical stimuli and transmit signals for central processing of pain sensation. Estrogen receptors (ERs) are also expressed on nociceptors in the TG and DRG, and there is ample literature to suggest that activation of ERs can influence pain mechanisms. However, the mechanism for ER modulation of nociceptor activity is incompletely understood. The aim of this study was to characterize the effect of 17β-estradiol (17β-E2) on signaling of the inflammatory mediator bradykinin (BK) in primary cultures of rat sensory neurons and a behavioral model of thermal allodynia in rats. Here, we show that exposure to 17β-E2 rapidly (within 15 min) enhanced responses to BK in vitro and in vivo. The 17β-E2-mediated enhancement of BK signaling was not blocked by the transcription inhibitor anisomycin and was mediated by a membrane-associated ER. The effect of 17β-E2 to enhance BK responses required activation of β1-containing, RGD-binding integrins. These data show that 17β-E2 rapidly enhances inflammatory mediator responses both in vitro and in vivo and suggest that 17β-E2 acting at primary sensory pain neurons may participate in regulating the sensitivity of women to painful stimuli.
Footnotes
This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants R01-NS055835, R01-NS061884, R01-NS058655], the National Institute of Dental and Craniofacial Research [COSTAR Training Grant T32DE14318] (to M.P.R.), the Texas Advanced Research Program [Grant 003659-0023], and The Oral and Maxillofacial Surgery Foundation.
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.167445.
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ABBREVIATIONS:
- TG
- trigeminal ganglia
- DRG
- dorsal root ganglia
- BK
- bradykinin
- 17β-E2
- 17β-estradiol
- PWL
- paw withdrawal latency
- ER
- estrogen receptor
- OVX
- ovariectomized
- DMSO
- dimethyl sulfoxide
- BSA
- bovine serum albumin
- HBSS
- Hank's balanced salt solution
- IP
- inositol phosphate
- PLC
- phospholipase C.
- Received February 23, 2010.
- Accepted July 19, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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