{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:38:57Z","timestamp":1793072337983,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["22K09020"],"award-info":[{"award-number":["22K09020"]}]},{"name":"JSPS KAKENHI","award":["19K09323"],"award-info":[{"award-number":["19K09323"]}]},{"name":"Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuropathic pain represents a critical challenge in medical research and clinical practice. Enhanced peripheral nerve activity and spinal dorsal horn neuronal firing are thought to contribute to the nociceptive hypersensitivities that are observed in chronic pain conditions, including those modeled by partial sciatic nerve ligation (PSNL). However, the detailed in vivo neuronal response dynamics and underlying mechanisms in the PSNL model remain to be fully clarified. To better understand these mechanisms, we evaluated dorsal root ganglion (DRG) and spinal dorsal horn neuronal activity in the PSNL model using in vivo approaches. Von Frey testing revealed sustained mechanical allodynia in PSNL animals; withdrawal thresholds were significantly reduced up to day 14 post-surgery. Immunohistochemistry revealed a stimulation-dependent increase in phosphorylated extracellular signal-regulated kinase (pERK)-positive neurons in the DRG, thereby indicating heightened peripheral nerve activity. Additionally, electrophysiological recordings demonstrated the enhanced firing of spinal dorsal horn neurons in response to the same stimuli. Notably, DRG pERK expression changes correlated with spinal neuronal firing frequency. Together, these findings suggest that peripheral nerve activity drives spinal neuronal sensitization, thus elucidating both pain mechanisms in the PSNL model and activity-dependent signaling in neuropathic pain.<\/jats:p>","DOI":"10.3390\/ijms27010124","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T16:19:26Z","timestamp":1766420366000},"page":"124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In Vivo Assessment of Peripheral and Spinal Neuronal Activity in the PSNL Model: Insights into Neuropathic Pain Mechanisms"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-1348","authenticated-orcid":false,"given":"Daisuke","family":"Uta","sequence":"first","affiliation":[{"name":"Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2426-7343","authenticated-orcid":false,"given":"Takuya","family":"Yamane","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Toyama, Japan"},{"name":"Neuroscience, Drug Discovery & Disease Research Laboratory, Shionogi & Co., Ltd., Toyonaka 561-0825, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sosuke","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Neuroscience, Drug Discovery & Disease Research Laboratory, Shionogi & Co., Ltd., Toyonaka 561-0825, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Kasai","sequence":"additional","affiliation":[{"name":"Neuroscience, Drug Discovery & Disease Research Laboratory, Shionogi & Co., Ltd., Toyonaka 561-0825, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2684-3666","authenticated-orcid":false,"given":"Toshiaki","family":"Kume","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/S0140-6736(21)00393-7","article-title":"Chronic pain: An update on burden, best practices, and new advances","volume":"397","author":"Cohen","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/j.pain.0000000000001390","article-title":"The IASP classification of chronic pain for ICD-11: Chronic primary pain","volume":"160","author":"Nicholas","year":"2019","journal-title":"Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17002","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","volume":"3","author":"Colloca","year":"2017","journal-title":"Nat. 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