Peptidergic intraepidermal nerve fibers in the skin contribute to the neuropathic pain in paclitaxel-induced peripheral neuropathy.

Abstract Paclitaxel in chemotherapy-induced peripheral neuropathy (CIPN) is predominantly with a dose-limiting effect on neuropathic pain in clinical strategy. In the present study, the relationship between the neuropathic pain and nerve degeneration in paclitaxel CIPN was investigated. Adult male Sprague–Dawley (SD) rats were divided into three paclitaxel groups (0.5, 1.0, 2.0 mg/kg) and a vehicle group with four intraperitoneal (i.p.) injections on alternating days. Our results demonstrated that the paclitaxel groups significantly exhibited the reductions of thermal hyperalgesia and mechanical allodynia. The neurotoxicity of paclitaxel conveyed the degeneration of intraepidermal nerve fibers (IENFs) in hindpaw glabrous skin. Nevertheless, the influence of paclitaxel to the peptidergic IENFs are even unknown. The skin innervation of protein gene product 9.5 (PGP 9.5)-immunoreactive (IR) IENFs in paclitaxel groups revealed the decreasing levels of density (73.54 ± 0.72%, 63.17 ± 1.77%, 61.79 ± 2.68%, respectively; vs. vehicle group, p p p r 2  = 0.77, p r 2  = 0.75, p r 2  = 0.28, p  = 0.0001, respectively) and mechanical thresholds ( r 2  = 0.43, p r 2  = 0.73, p r 2  = 0.40, p