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The purpose of this study was to explore the role of endothelin in neuropathic pain. Endothelins (ET) are a family (ET-1, ET-2, ET-3) of ubiquitously expressed peptides involved in control of vascular tone. Injected ET-1 causes intense pain via activation of ETA receptors, modulated by analgesic signals initiated by ETB receptor activation. Using a rat model of chronic constriction injury of the sciatic nerve, we found that pharmacologic ETA receptor antagonism acutely and significantly reduced thermal and mechanical hyperalgesic responses 5 days after injury. Furthermore, ET-1 and the ETA receptor are locally upregulated at the site of chronic constriction injury at both the message and the protein levels, suggesting that ET-1 may be involved in establishing pain after the injury. These data point to ET-1 as an important mediator of pain in general and suggest that ETA antagonism deserves study as a potential novel therapy for neuropathic pain.

“It seems to me, now,” reflected Troy Perry, four years after founding a successful new Protestant denomination, “that it must have been a matter of timing, and I think that it was fate, too! God chose me for my mission at a time when He knew the world would respond, once the need was made clear.” While the question of divine ordination is a bit outside the scholar's jurisdiction, the question of timing is a crucial one for historical inquiry, and Perry's remarks show an insightful awareness that the success of the Universal Fellowship of Metropolitan Community Churches (UFMCC) was due in large part to timing. As with any successful religious group, however, the seeds of the UFMCC germinated, sprouted, and grew as a result of a multitude of interconnected factors, including both external back-ground factors in American society at large and internal factors within the UFMCC itself. This article relates the history and early growth of the UFMCC to this constellation of factors in order to gain a clearer understanding of both the denomination itself and the social changes of which it was an integral part.

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