title: Promotion of thermal analgesia and neuropeptidergic skin reinnervation by 4-methylcatechol in resiniferatoxin-induced neuropathy.
abstract: To investigate whether 4-methylcatechol (4MC) could decrease the duration of the thermosensation disorder and promote the innervation of peptidergic intraepidermal nerve fibers (IENFs), we developed a resiniferatoxin (RTX)-induced neuropathic mouse model with thermal analgesia and skin denervation that was followed by daily 4MC treatment. On day 7 after RTX administration (RTXd7), the substance P (SP)(+) IENFs were completely depleted compared with the vehicle group (p < 0.0001), whereas the calcitonin gene-related peptide (CGRP)(+) IENFs were dramatically, but not completely, depleted (p < 0.0001). While SP(+) IENFs remained depleted (p = 0.0043), CGRP(+) IENFs were recovered by RTXd84 (p = 0.78). 4MC had no effect on the reinnervation of SP(+) IENFs, but markedly promoted the reinnervation of CGRP(+) IENFs on RTXd35 (p = 0.035). On RTXd56, CGRP(+) IENFs were comparable with the vehicle group (p = 0.39). In addition, 4MC normalized thermal analgesia on RTXd35 compared with RTX group (p = 0.007). In the current study, the significant promotion of reinnervation of CGRP(+) IENFs and thermal latencies on RTXd35 by 4MC indicated that CGRP(+) IENFs were responsible for the thermal transmission in chronic phase of RTX-induced neuropathy.
authors.affiliation: Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan. ylhsieh@kmu.edu.tw
authors.forename: Tin-Hsin
authors.initials: TH
authors.lastname: Hsiao
authors.forename: Yaw-Syan
authors.initials: YS
authors.lastname: Fu
authors.forename: Wan-Yi
authors.initials: WY
authors.lastname: Ho
authors.forename: Tzi-Hsuan
authors.initials: TH
authors.lastname: Chen
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Hsieh
mesh_terms: D000698:Analgesia / Q000379:methods*; D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D003714:Denervation / Q000379:methods; D004195:Disease Models, Animal; D004224:Diterpenes / Q000633:toxicity*; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009416:Nerve Regeneration / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity; D017288:Pain Threshold / Q000187:drug effects*; D012867:Skin / Q000294:innervation*
chemical_list: D002396:Catechols; D004224:Diterpenes; D018696:Neuroprotective Agents; D009498:Neurotoxins; C018599:4-methylcatechol; C024353:resiniferatoxin
keywords: 4-Methylcatechol; Calcitonin gene-related peptide; Resiniferatoxin; Substance P; Transient receptor potential vanilloid subtype 1
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