{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:57:08Z","timestamp":1785243428160,"version":"3.55.0"},"reference-count":181,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:00:00Z","timestamp":1665187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis is considered a multifactorial and heterogeneous systemic disease with many underlying pathologic mechanisms having been elucidated; however, the pathomechanism is far from entirely known. This opinion article will demonstrate the potential relevance of the somatosensory Piezo2 microinjury-induced quad-phasic non-contact injury model in psoriasis through a multidisciplinary approach. The primary injury is suggested to be on the Piezo2-containing somatosensory afferent terminals in the Merkel cell\u2013neurite complex, with the concomitant impairment of glutamate vesicular release machinery in Merkel cells. Part of the theory is that the Merkel cell\u2013neurite complex contributes to proprioception; hence, to the stretch of the skin. Piezo2 channelopathy could result in the imbalanced control of Piezo1 on keratinocytes in a clustered manner, leading to dysregulated keratinocyte proliferation and differentiation. Furthermore, the author proposes the role of mtHsp70 leakage from damaged mitochondria through somatosensory terminals in the initiation of autoimmune and autoinflammatory processes in psoriasis. The secondary phase is harsher epidermal tissue damage due to the primary impaired proprioception. The third injury phase refers to re-injury and sensitization with the derailment of healing to a state when part of the wound healing is permanently\u00a0kept alive due to genetical predisposition and environmental risk factors. Finally, the quadric damage phase is associated with the aging process and associated inflammaging. In summary, this opinion piece postulates that the primary microinjury of our \u201csixth sense\u201d, or the Piezo2 channelopathy of the somatosensory terminals contributing to proprioception, could be the principal gateway to pathology due to the encroachment of our preprogrammed genetic encoding.<\/jats:p>","DOI":"10.3390\/ijms231911940","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Psoriasis, Is It a Microdamage of Our \u201cSixth Sense\u201d? A Neurocentric View"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-1306","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Sonkodi","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Sport Medicine, Hungarian University of Sports Sciences, 1123 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1001\/jamadermatol.2021.2007","article-title":"Psoriasis Prevalence in Adults in the United States","volume":"157","author":"Armstrong","year":"2021","journal-title":"JAMA Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1093\/pcmedi\/pbz011","article-title":"Genetics of psoriasis: A basis for precision medicine","volume":"2","author":"Ran","year":"2019","journal-title":"Precis. Clin. 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