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Kaohsiung J Med Sci. 2013 Aug;29(8):405-11. doi: 10.1016/j.kjms.2012.12.001. Epub 2013 Feb 6.

Promotion of thermal analgesia and neuropeptidergic skin reinnervation by 4-methylcatechol in resiniferatoxin-induced neuropathy.

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  • 1Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan.


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.

Copyright © 2012. Published by Elsevier B.V.


4-Methylcatechol; Calcitonin gene-related peptide; Resiniferatoxin; Substance P; Transient receptor potential vanilloid subtype 1

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