title: Autonomic fibre sprouting and changes in nociceptive sensory innervation in the rat lower lip skin following chronic constriction injury.
abstract: In this study we used immunocytochemistry to investigate whether autonomic fibres sprouted in the skin of the lower lip in a rat model of neuropathic pain. We used a bilateral chronic constriction injury (CCI) of the mental nerve (MN), a branch of the trigeminal nerve. In this model, we also studied the accompanying changes in peptidergic [calcitonin gene-related peptide (CGRP)-immunoreactive] sensory fibres, as well as in trkA receptor immunoreactivity in the sensory nerves. Autonomic (sympathetic and parasympathetic) fibre sprouting was first observed 1 week post-injury with a peak in the number of sprouted fibres occurring at 4 and 6 weeks post-CCI. CGRP-IR fibres almost disappeared at 2 weeks post-CCI, but quickly sprouted, leading to a significant peak above sham levels 4 weeks post-injury. trkA receptor expression was found to be up-regulated in small cutaneous nerves 4 weeks post-CCI, returning to sham levels by 8 weeks post-CCI. There was no sympathetic fibre sprouting in the trigeminal ganglion following CCI. At 4 weeks post-CCI, rats displayed spontaneous, directed grooming to the area innervated by the MN that was not seen in sham animals, which we interpreted as a sign of spontaneous pain or dysesthesiae. Collectively, our findings indicate that as a result of autonomic sprouting due to CCI of the MN, remaining intact nociceptive fibres may potentially develop sensitivity to sympathetic and parasympathetic stimulation, which may have a role in the generation of abnormal pain following nerve injury.
authors.affiliation: Department of Pharmacology & Therapeutics, McGill University, 3655 Prom. Sir-William-Osler, Montreal, Quebec, Canada H3G 1Y6.
authors.forename: C
authors.initials: C
authors.lastname: Grelik
authors.forename: G J
authors.initials: GJ
authors.lastname: Bennett
authors.forename: A
authors.initials: A
authors.lastname: Ribeiro-da-Silva
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000166:cytology / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005156:Facial Neuralgia / Q000503:physiopathology*; D006120:Grooming; D008046:Lip / Q000294:innervation*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D009408:Nerve Compression Syndromes / Q000503:physiopathology*; D009412:Nerve Fibers / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism / Q000648:ultrastructure; D009619:Nociceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000294:innervation; D012668:Trigeminal Ganglion / Q000166:cytology; D050494:Vesicular Acetylcholine Transport Proteins; D014743:Videotape Recording
chemical_list: D026901:Membrane Transport Proteins; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D004299:Dopamine beta-Hydroxylase; D015740:Calcitonin Gene-Related Peptide