{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:22:39Z","timestamp":1760239359224,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002911","name":"Universidad Complutense de Madrid","doi-asserted-by":"publisher","award":["PR75\/18-21593"],"award-info":[{"award-number":["PR75\/18-21593"]}],"id":[{"id":"10.13039\/501100002911","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["BFU2011-26253, BFU2015-70067-REDC, SAF2016-78892"],"award-info":[{"award-number":["BFU2011-26253, BFU2015-70067-REDC, SAF2016-78892"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We have investigated whether the stress response mediated by the adrenal medulla in rats subjected to chronic constriction injury of the sciatic nerve (CCI) modulates their nocifensive behavior. Treatment with SK29661 (300 mg\/kg; intraperitoneal (I.P.)), a selective inhibitor of phenylethanolamine N-methyltransferase (PNMT) that converts noradrenaline (NA) into adrenaline (A), fully reverted mechanical allodynia in the injured hind paw without affecting mechanical sensitivity in the contralateral paw. The effect was fast and reversible and was associated with a decrease in the A to NA ratio (A\/NA) in the adrenal gland and circulating blood, an A\/NA that was elevated by CCI. 1,2,3,4-tetrahydroisoquinoline-7-sulfonamide (SKF29661) did not affect exocytosis evoked by Ca2+ entry as well as major ionic conductances (voltage-gated Na+, Ca2+, and K+ channels, nicotinic acetylcholine receptors) involved in stimulus-secretion coupling in chromaffin cells, suggesting that it acted by changing the relative content of the two adrenal catecholamines. Denervation of the adrenal medulla by surgical splanchnectomy attenuated mechanical allodynia in neuropathic animals, hence confirming the involvement of the adrenal medulla in the pathophysiology of the CCI model. Inhibition of PNMT appears to be an effective and probably safe way to modulate adrenal medulla activity and, in turn, to alleviate pain secondary to the injury of a peripheral nerve.<\/jats:p>","DOI":"10.3390\/ijms21218325","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T09:09:30Z","timestamp":1604653770000},"page":"8325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Adrenal Medulla Modulates Mechanical Allodynia in a Rat Model of Neuropathic Pain"],"prefix":"10.3390","volume":"21","author":[{"given":"Marina","family":"Arribas-Bl\u00e1zquez","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Veterinary Faculty and Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0595-073X","authenticated-orcid":false,"given":"Luis Alcides","family":"Olivos-Or\u00e9","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Veterinary Faculty and Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Victoria","family":"Barahona","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Veterinary Faculty and Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aneta","family":"Wojnicz","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Instituto Te\u00f3filo Hernando, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6628-6097","authenticated-orcid":false,"given":"Ricardo","family":"De Pascual","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Instituto Te\u00f3filo Hernando, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"S\u00e1nchez de la Muela","sequence":"additional","affiliation":[{"name":"Department of Animal Medicine and Surgery, Veterinary Faculty, Universidad Complutense de Madrid, 20040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio G.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Instituto Te\u00f3filo Hernando, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-9190","authenticated-orcid":false,"given":"Antonio R.","family":"Artalejo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Veterinary Faculty and Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1210\/jcem-6-2-117","article-title":"The general adaptation syndrome and the diseases of adaptation1","volume":"6","author":"Selye","year":"1946","journal-title":"J. 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