{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:11:33Z","timestamp":1791303093812,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,3,3]],"date-time":"2009-03-03T00:00:00Z","timestamp":1236038400000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To develop and validate a model of cutaneous allodynia triggered by dural inflammation for pain associated with headaches. To explore neural mechanisms underlying cephalic and extracephalic allodynia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Inflammatory mediators (IM) were applied to the dura of unanesthetized rats via previously implanted cannulas, and sensory thresholds of the face and hind\u2010paws were characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IM elicited robust facial and hind\u2010paw allodynia, which peaked within 3 hours. These effects were reminiscent of cutaneous allodynia seen in patients with migraine or other primary headache conditions, and were reversed by agents used clinically in the treatment of migraine, including sumatriptan, naproxen, and a calcitonin gene\u2013related peptide antagonist. Consistent with clinical observations, the allodynia was unaffected by a neurokinin\u20101 antagonist. Having established facial and hind\u2010paw allodynia as a useful animal surrogate of headache\u2010associated allodynia, we next showed that blocking pain\u2010facilitating processes in the rostral ventromedial medulla (RVM) interfered with its expression. Bupivacaine, destruction of putative pain\u2010facilitating neurons, or block of cholecystokinin receptors prevented or significantly attenuated IM\u2010induced allodynia. Electrophysiological studies confirmed activation of pain\u2010facilitating RVM \u201con\u201d cells and transient suppression of RVM \u201coff\u201d cells after IM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Facial and hind\u2010paw allodynia associated with dural stimulation is a useful surrogate of pain associated with primary headache including migraine and may be exploited mechanistically for development of novel therapeutic strategies for headache pain. The data also demonstrate the requirement for activation of descending facilitation from the RVM for the expression of cranial and extracranial cutaneous allodynia, and are consistent with a brainstem generator of allodynia associated with headache disorders. Ann Neurol 2009;65:184\u2013193<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.21537","type":"journal-article","created":{"date-parts":[[2009,3,3]],"date-time":"2009-03-03T08:23:34Z","timestamp":1236068614000},"page":"184-193","source":"Crossref","is-referenced-by-count":203,"title":["Medullary pain facilitating neurons mediate allodynia in headache\u2010related pain"],"prefix":"10.1002","volume":"65","author":[{"given":"Rebecca M.","family":"Edelmayer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd 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