Artemin induced functional recovery and reinnervation after partial nerve injury

Ruizhong Wang, Anthony Rossomando, Dinah W Y Sah, Michael H. Ossipov, Tamara King, Frank Porreca

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Systemic artemin promotes regeneration of dorsal roots to the spinal cord after crush injury. However, it is unclear whether systemic artemin can also promote peripheral nerve regeneration, and functional recovery after partial lesions distal to the dorsal root ganglion (DRG) remains unknown. In the present investigation, male Sprague Dawley rats received axotomy, ligation, or crush of the L5 spinal nerve or sham surgery. Starting the day of injury, animals received intermittent subcutaneous artemin or vehicle across 2 weeks. Sensory thresholds to tactile or thermal stimuli were monitored for 6 weeks after injury. Immunohistochemical analyses of the DRG and nerve regeneration were performed at the 6-week time point. Artemin transiently reversed tactile and thermal hypersensitivity after axotomy, ligation, or crush injury. Thermal and tactile hypersensitivity reemerged within 1 week of treatment termination. However, artemin-treated rats with nerve crush, but not axotomy or ligation, subsequently showed gradual return of sensory thresholds to preinjury baseline levels by 6 weeks after injury. Artemin normalized labeling for NF200, IB4, and CGRP in nerve fibers distal to the crush injury, suggesting persistent normalization of nerve crush-induced neurochemical changes. Sciatic and intradermal administration of dextran or cholera toxin B distal to the crush injury site resulted in labeling of neuronal profiles in the L5 DRG, suggesting regeneration functional restoration of nonmyelinated and myelinated fibers across the injury site into cutaneous tissue. Artemin also diminished ATF3 and caspase 3 expression in the L5 DRG, suggesting persistent neuroprotective actions. A limited period of artemin treatment elicits disease modification by promoting sensory reinnervation of distal territories and restoring preinjury sensory thresholds.

Original languageEnglish (US)
Pages (from-to)476-484
Number of pages9
JournalPain
Volume155
Issue number3
DOIs
StatePublished - Mar 2014

Fingerprint

Spinal Ganglia
Sensory Thresholds
Axotomy
Touch
Nerve Crush
Ligation
Nerve Regeneration
Hot Temperature
Wounds and Injuries
Regeneration
Hypersensitivity
Spinal Nerves
Spinal Nerve Roots
Cholera Toxin
Dextrans
Peripheral Nerves
Nerve Fibers
Caspase 3
Sprague Dawley Rats
Spinal Cord

Keywords

  • Artemin
  • Hyperalgesia
  • Peripheral nerve injury
  • Regeneration
  • Sensory neurons

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine
  • Neurology
  • Pharmacology

Cite this

Wang, R., Rossomando, A., Sah, D. W. Y., Ossipov, M. H., King, T., & Porreca, F. (2014). Artemin induced functional recovery and reinnervation after partial nerve injury. Pain, 155(3), 476-484. https://doi.org/10.1016/j.pain.2013.11.007

Artemin induced functional recovery and reinnervation after partial nerve injury. / Wang, Ruizhong; Rossomando, Anthony; Sah, Dinah W Y; Ossipov, Michael H.; King, Tamara; Porreca, Frank.

In: Pain, Vol. 155, No. 3, 03.2014, p. 476-484.

Research output: Contribution to journalArticle

Wang, R, Rossomando, A, Sah, DWY, Ossipov, MH, King, T & Porreca, F 2014, 'Artemin induced functional recovery and reinnervation after partial nerve injury', Pain, vol. 155, no. 3, pp. 476-484. https://doi.org/10.1016/j.pain.2013.11.007
Wang, Ruizhong ; Rossomando, Anthony ; Sah, Dinah W Y ; Ossipov, Michael H. ; King, Tamara ; Porreca, Frank. / Artemin induced functional recovery and reinnervation after partial nerve injury. In: Pain. 2014 ; Vol. 155, No. 3. pp. 476-484.
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