{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:38:02Z","timestamp":1760146682474,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81100818"],"award-info":[{"award-number":["81100818"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In vitro experiments performed on dissociated dorsal root ganglion (DRG) neurons suggest the involvement of the hyperpolarization-activated cation current (Ih) in enhancing neuronal excitability, potentially contributing to neuropathic pain. However, the more confirmative in vivo information about how nerve injury interacts with Ih is lacking. In this study, Ih was recorded in vivo using the dynamic single-electrode voltage clamp (dSEVC) technique on L5 DRG neurons of normal rats and those seven days after spinal nerve axotomy (SNA). Compared to normal rats, SNA unexpectedly inhibited the activity of Ih channels on A-fiber DRG neurons: (a) the Ih current magnitude, density, and conductance were consistently diminished; and (b) the Ih activation velocity was slowed and the voltage for Ih activation was hyperpolarized. The half-activation voltage (V0.5) exhibited a negative shift, and the time constant for Ih activation was prolonged across all test potentials, indicating the reduced availability of Ih after SNA. To further investigate the mechanisms of SNA on Ih, the underlying HCN channels and the correlated mRNA were quantified and compared. The mRNA expression level of HCN1-4 was uniformly enhanced after SNA, which might have contributed to the increased cytoplasmic HCN1 intensity observed in both medium- and large-sized DRG neurons. This finding contradicted the functional reduction of Ih after SNA. Surprisingly, the HCN labeling pattern was altered after SNA: the labeling area of HCN1 and HCN2 at the membranous ring region of the axotomized large neurons became significantly thinner or absent. We concluded that the diminished ring immunoreactivity for HCN1 and HCN2 correlated with a reduced availability of Ih channels, elucidating the observed decrease in Ih in axotomized A-fiber neurons.<\/jats:p>","DOI":"10.3390\/ijms252312889","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T05:43:43Z","timestamp":1733118223000},"page":"12889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spinal Nerve Axotomy: Effects on Ih In Vivo and HCNs in DRG Neurons"],"prefix":"10.3390","volume":"25","author":[{"given":"Yuanlong","family":"Song","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan,430030, China"},{"name":"Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan,430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0642-1960","authenticated-orcid":false,"given":"Linlin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan,430030, China"},{"name":"Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan,430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S1474-4422(10)70143-5","article-title":"Neuropathic pain: Diagnosis, pathophysiological mechanisms, and treatment","volume":"9","author":"Baron","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.neuron.2015.03.003","article-title":"Dysfunction of cortical dendritic integration in neuropathic pain reversed by serotoninergic neuromodulation","volume":"86","author":"Santello","year":"2015","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.nbd.2017.07.005","article-title":"The brain-penetrant 5-HT(7) receptor agonist LP-211 reduces the sensory and affective components of neuropathic pain","volume":"106","author":"Santello","year":"2017","journal-title":"Neurobiol. 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