{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:33:28Z","timestamp":1771338808383,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"grant from the Sato Fund, Nihon University School of Dentistry","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"grant from Uemura Fund, Nihon University School of Dentistry","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"grant from Dental Research Center, Nihon University School of Dentistry","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"KAKENHI","award":["17K11654"],"award-info":[{"award-number":["17K11654"]}]},{"name":"KAKENHI","award":["18K09732"],"award-info":[{"award-number":["18K09732"]}]},{"name":"KAKENHI","award":["19K10049"],"award-info":[{"award-number":["19K10049"]}]},{"name":"Nihon University Multidisciplinary Research Grant","award":["18-014"],"award-info":[{"award-number":["18-014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Insulin-like growth factor-1 (IGF-1) is upregulated in the injured peripheral nerve bundle and controls nociceptive neuronal excitability associated with peripheral nerve injury. Here, we examined the involvement of IGF-1 signaling in orofacial neuropathic pain following infraorbital nerve injury (IONI) in rats. IONI promoted macrophage accumulation in the injured ION, as well as in the ipsilateral trigeminal ganglion (TG), and induced mechanical allodynia of the whisker pad skin together with the enhancement of neuronal activities in the subnucleus caudalis of the spinal trigeminal nucleus and in the upper cervical spinal cord. The levels of IGF-1 released by infiltrating macrophages into the injured ION and the TG were significantly increased. The IONI-induced the number of transient receptor potential vanilloid (TRPV) subfamily type 4 (TRPV4) upregulation in TRPV subfamily type 2 (TRPV2)-positive small-sized, and medium-sized TG neurons were inhibited by peripheral TRPV2 antagonism. Furthermore, the IONI-induced mechanical allodynia was suppressed by TRPV4 antagonism in the whisker pad skin. These results suggest that IGF-1 released by macrophages accumulating in the injured ION binds to TRPV2, which increases TRPV4 expression in TG neurons innervating the whisker pad skin, ultimately resulting in mechanical allodynia of the whisker pad skin.<\/jats:p>","DOI":"10.3390\/ijms20246360","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T03:19:36Z","timestamp":1576811976000},"page":"6360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Increase in IGF-1 Expression in the Injured Infraorbital Nerve and Possible Implications for Orofacial Neuropathic Pain"],"prefix":"10.3390","volume":"20","author":[{"given":"Shiori","family":"Sugawara","sequence":"first","affiliation":[{"name":"Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan"},{"name":"Department of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0965-6498","authenticated-orcid":false,"given":"Masamichi","family":"Shinoda","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7750-0674","authenticated-orcid":false,"given":"Yoshinori","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroto","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo 101-8310, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnostic Sciences, Nihon University School of Dentistry, Tokyo 101-8310, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asako","family":"Kubo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikuko","family":"Shibuta","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Nihon University School of Dentistry, Tokyo 101-8310, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9498-3014","authenticated-orcid":false,"given":"Akira","family":"Toyofuku","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nihon University School of Dentistry, Tokyo 101-8310, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lin, C.S., Wu, S.Y., Huang, H.Y., and Lai, Y.L. 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