Peripheral nerve injury leads to the establishment of a novel pattern of sympathetic fibre innervation in the rat skin

J Comp Neurol. 2000 Jun 26;422(2):287-96. doi: 10.1002/(sici)1096-9861(20000626)422:2<287::aid-cne9>;2-e.


Peripheral nerve injury has been shown to result in sympathetic fibre sprouting around dorsal root ganglia (DRG) neurons. It has been suggested that this anomalous sympathetic fibre innervation of the DRG plays a role in neuropathic pain. Other studies have suggested an interaction between sympathetic and sensory fibres more peripherally. To date, no anatomical study of these possible interactions in the terminal fields of sensory and sympathetic fibres has been performed; therefore, the authors set out to study them in the rat lower lip after bilateral lesions of a sensory nerve, the mental nerve (MN). Immunocytochemistry for both substance P (SP) and dopamine-beta-hydroxylase (DbetaH) was performed. Within the first week post-MN lesions, the SP-immunoreactive (IR) fibres had degenerated almost completely, whereas DbetaH-IR fibres were found in the upper dermis, an area from which they normally are absent. These DbetaH-IR fibres were present in the upper dermis at all postsurgery times studied (1, 2, 3, 4, 6, and 8 weeks). It is noteworthy that, although, by week 6 post-MN lesions, SP-IR fibre reinnervation of the lower lip was occurring, the DbetaH-IR fibres still were present in the upper dermis. Quantification revealed that the migration and branching of the DbetaH-IR fibres into the upper dermis occurred gradually and was most significant at 4 weeks post-MN lesions, as demonstrated by the fact that the DbetaH-IR fibres were found 169.6 +/- 91.4 microm away from the surface of the skin compared with 407.1 +/- 78.4 microm away in sham-operated animals. These findings suggest that the ectopic innervation of the upper dermis by sympathetic fibres may be important in the genesis of neuropathic pain through the interactions of sympathetic and SP-containing sensory fibres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / pathology
  • Axotomy / adverse effects*
  • Denervation
  • Dopamine beta-Hydroxylase / metabolism
  • Male
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Nerve Regeneration / physiology*
  • Neuronal Plasticity / physiology*
  • Neurons, Afferent / metabolism
  • Neurons, Afferent / pathology
  • Nociceptors / injuries
  • Nociceptors / pathology
  • Nociceptors / physiopathology
  • Peripheral Nerve Injuries*
  • Peripheral Nerves / pathology
  • Peripheral Nerves / physiopathology*
  • Rats
  • Rats, Wistar
  • Skin / innervation*
  • Skin / pathology
  • Skin / physiopathology*
  • Substance P / metabolism
  • Sympathetic Fibers, Postganglionic / injuries*
  • Sympathetic Fibers, Postganglionic / pathology
  • Sympathetic Fibers, Postganglionic / physiopathology*
  • Time Factors
  • Trigeminal Nerve / pathology
  • Trigeminal Nerve / physiopathology
  • Trigeminal Nerve Injuries


  • Substance P
  • Dopamine beta-Hydroxylase