Autonomic fibre sprouting and changes in nociceptive sensory innervation in the rat lower lip skin following chronic constriction injury

Eur J Neurosci. 2005 May;21(9):2475-87. doi: 10.1111/j.1460-9568.2005.04089.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autonomic Nervous System / cytology
  • Autonomic Nervous System / physiology*
  • Calcitonin Gene-Related Peptide / metabolism
  • Chronic Disease
  • Disease Models, Animal
  • Dopamine beta-Hydroxylase / metabolism
  • Facial Neuralgia / physiopathology*
  • Grooming
  • Lip / innervation*
  • Male
  • Membrane Transport Proteins / metabolism
  • Nerve Compression Syndromes / physiopathology*
  • Nerve Fibers / physiology
  • Neurons, Afferent / metabolism
  • Neurons, Afferent / ultrastructure
  • Nociceptors / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Skin / innervation
  • Trigeminal Ganglion / cytology
  • Vesicular Acetylcholine Transport Proteins
  • Videotape Recording

Substances

  • Membrane Transport Proteins
  • Slc18a3 protein, rat
  • Vesicular Acetylcholine Transport Proteins
  • Dopamine beta-Hydroxylase
  • Calcitonin Gene-Related Peptide