{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:21:25Z","timestamp":1785392485137,"version":"3.55.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,7,6]]},"abstract":"<jats:p>Control of expression of molecular receptors for chemical\n messengers and modulation of these receptors\u2019 activity are now\n established as ways to alter cellular reaction. This paper extends\n these mechanisms to the arena of pathological pain by presenting the\n hypothesis that increased expression of \u03b1-adrenergic receptors in\n primary afferent neurons is part of the etiology of pain in classical\n causalgia. It is argued that partial denervation by lesion of\n peripheral nerve or by tissue destruction induces a change in\n peripheral nociceptors, making them excitable by sympathetic activity\n and adrenergic substances. This excitation is mediated by\n \u03b1-adrenergic receptors and has a time course reminiscent of\n experimental denervation supersensitivity. The change in neuronal\n phenotype is demonstrable after lesions of mixed nerves or of the\n sympathetic postganglionic supply. Similar partial denervations also\n produce a substantial increase in the number of dorsal root ganglion\n neurons evidencing the presence of \u03b1-adrenergic receptors. The\n hypothesis proposes the increased presence of \u03b1-adrenergic receptors\n in primary afferent neurons to result from an altered gene expression\n triggered by cytokines\/growth factors produced by disconnection of\n peripheral nerve fibers from their cell bodies. These additional\n adrenergic receptors are suggested to make nociceptors and other\n primary afferent neurons excitable by local or circulating\n norepinephrine and epinephrine. For central pathways, the adrenergic\n excitation would be equivalent to that produced by noxious events and\n would consequently evoke pain. In support, evidence is cited for a form\n of denervation supersensitivity in causalgia and for increased\n expression of human \u03b1-adrenergic receptors after loss of sympathetic\n activity.<\/jats:p>","DOI":"10.1073\/pnas.96.14.7664","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"7664-7667","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":57,"title":["Causalgia, pathological pain, and adrenergic receptors"],"prefix":"10.1073","volume":"96","author":[{"given":"Edward R.","family":"Perl","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Physiology, CB 7545, University of\r North Carolina, Chapel Hill, NC 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