{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:36:06Z","timestamp":1790825766546,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Pain and nociception are different phenomena. Nociception is the result of complex activity in sensory pathways. On the other hand, pain is the effect of interactions between nociceptive processes, and cognition, emotions, as well as the social context of the individual. Alterations in the nociceptive route can have different genesis and affect the entire sensorial process. Genetic problems in nociception, clinically characterized by reduced or absent pain sensitivity, compose an important chapter within pain medicine. This chapter encompasses a wide range of very rare diseases. Several genes have been identified. These genes encode the Nav channels 1.7 and 1.9 (SCN9A, and SCN11A genes, respectively), NGF\u03b2 and its receptor tyrosine receptor kinase A, as well as the transcription factor PRDM12, and autophagy controllers (TECPR2). Monogenic disorders provoke hereditary sensory and autonomic neuropathies. Their clinical pictures are extremely variable, and a precise classification has yet to be established. Additionally, pain insensitivity is described in diverse numerical and structural chromosomal abnormalities, such as Angelman syndrome, Prader Willy syndrome, Chromosome 15q duplication syndrome, and Chromosome 4 interstitial deletion. Studying these conditions could be a practical strategy to better understand the mechanisms of nociception and investigate potential therapeutic targets against pain.<\/jats:p>","DOI":"10.3390\/pathophysiology29030035","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:15:26Z","timestamp":1659485726000},"page":"435-452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Pathophysiology of Nociception and Rare Genetic Disorders with Increased Pain Threshold or Pain Insensitivity"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5236-3132","authenticated-orcid":false,"given":"Marco","family":"Cascella","sequence":"first","affiliation":[{"name":"Division of Anesthesia, Istituto Nazionale Tumori IRCCS\u2014Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Muzio","sequence":"additional","affiliation":[{"name":"Division of Infantile Neuropsychiatry, UOMI-Maternal and Infant Health, ASL NA3\/Sud, 80059 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-3594","authenticated-orcid":false,"given":"Federica","family":"Monaco","sequence":"additional","affiliation":[{"name":"Division of Anesthesia, Istituto Nazionale Tumori IRCCS\u2014Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9981-5431","authenticated-orcid":false,"given":"Davide","family":"Nocerino","sequence":"additional","affiliation":[{"name":"Division of Anesthesia, Istituto Nazionale Tumori IRCCS\u2014Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-3855","authenticated-orcid":false,"given":"Alessandro","family":"Ottaiano","sequence":"additional","affiliation":[{"name":"SSD Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori IRCCS\u2014Fondazione G. Pascale, 80130 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8158-7509","authenticated-orcid":false,"given":"Francesco","family":"Perri","sequence":"additional","affiliation":[{"name":"Medical and Experimental Head and Neck Oncology Unit, Istituto Nazionale Tumori IRCCS\u2014Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo Antonio","family":"Innamorato","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Pain Unit, Santa Maria delle Croci Hospital, AUSL Romagna, Viale Vincenzo Randi 5, 48121 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref_2","unstructured":"Zelaya, E.C., Dahlhamer, M.J., Lucas, W.J., and Connor, E. (2021, November 23). Chronic Pain and High-Impact Chronic Pain among U.S. Adults, 2019. 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