title: Paracrine-like excitation of low-threshold mechanoceptive C-fibers innervating rat hairy skin is mediated by substance P via NK-1 receptors.
abstract: We reported previously that C-fibers innervating rat skin can be excited by short trains of electrical shocks ('tetanus') applied to neighboring nerves. Since these nerves were disconnected from the CNS, the cross-talk is located peripherally. Here we tested if low-threshold mechanoceptive (LTM) C-fibers can be excited by this cross-talk and if this process is mediated by substance P (SP) via neurokinin-1 (NK-1) receptors. In urethane anesthetized rats we found that 80% (56/71) of LTM C-fibers, recorded in the lateral cutaneous branch of the dorsal ramus (CBDR) of T10 spinal nerve, were excited by a 10s, 20 Hz tetanus of the T9 CBDR. Compared to the spontaneous pre-tetanic firing frequency of 1.62+/-0.40 impulses/30s, the frequency significantly increased to 3.74+/-0.99, 3.17+/-0.69 and 2.92+/-0.63 impulses/30s, at 30, 60 and 90 s after the tetanus, respectively, and declined to the baseline frequency thereafter. When injected into their receptive fields, SP mimicked the tetanically induced increase of firing rate, whereas the NK-1 receptor antagonist WIN 51708 blocked the excitation in most fibers. The excitation was significantly diminished in adult rats that were neonatally treated with capsaicin, a treatment that destroys most SP-expressing afferent fibers. Thus, we conclude that peptidergic primary afferents are functionally linked with adjacent LTM C-fibers in a non-synaptic, paracrine-like signaling pathway via SP and NK-1 receptors, and perhaps also other agents as well. We propose that this cross-talk has evolved as a mechanism regulating the mechanoceptive characteristics of LTM C-fibers, presumably contributing to pain sensation elicited by tactile stimuli ('allodynia').
authors.affiliation: Faculty of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China. shzhang713@zju.edu.cn
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Zhang
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Sun
authors.forename: Ze'ev
authors.initials: Z
authors.lastname: Seltzer
authors.forename: Dong-Yuan
authors.initials: DY
authors.lastname: Cao
authors.forename: Hui-Sheng
authors.initials: HS
authors.lastname: Wang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000528:radiation effects; D000731:Androstanes / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012867:Skin / Q000294:innervation*; D013373:Substance P / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000731:Androstanes; D001562:Benzimidazoles; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C086111:WIN 51708; D013373:Substance P; D002211:Capsaicin