Journal article
Acute exercise prevents the development of neuropathic pain and the sprouting of non-peptidergic (GDNF- and artemin-responsive) c-fibers after spinal cord injury
Experimental neurology, v 255, pp 38-48
May 2014
PMID: 24560714
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Spinal cord injury (SCI) impaired sensory fiber transmission leads to chronic, debilitating neuropathic pain. Sensory afferents are responsive to neurotrophic factors, molecules that are known to promote survival and maintenance of neurons, and regulate sensory neuron transduction of peripheral stimuli. A subset of primary afferent fibers responds only to the glial cell-line derived neurotrophic factor (GDNF) family of ligands (GFLs) and is non-peptidergic. In peripheral nerve injury models, restoration of GDNF or artemin (another GFL) to pre-injury levels within the spinal cord attenuates neuropathic pain. One non-invasive approach to increase the levels of GFLs in the spinal cord is through exercise (Ex), and to date exercise training is the only ameliorative, non-pharmacological treatment for SCI-induced neuropathic pain. The purpose of this study was 3-fold: 1) to determine whether exercise affects the onset of SCI-induced neuropathic pain; 2) to examine the temporal profile of GDNF and artemin in the dorsal root ganglia and spinal cord dorsal horn regions associated with forepaw dermatomes after SCI and Ex; and 3) to characterize GFL-responsive sensory fiber plasticity after SCI and Ex. Adult, female, Sprague-Dawley rats received a moderate, unilateral spinal cord contusion at C5. A subset of rats was exercised (SCI+Ex) on automated running wheels for 20min, 5days/week starting at 5days post-injury (dpi), continuing until 9 or 37dpi. Hargreaves' and von Frey testing was performed preoperatively and weekly post-SCI. Forty-two percent of rats in the unexercised group exhibited tactile allodynia of the forepaws while the other 58% retained normal sensation. The development of SCI-induced neuropathic pain correlated with a marked decrease in the levels of GDNF and artemin in the spinal cord and DRGs. Additionally, a dramatic increase in the density and the distribution throughout the dorsal horn of GFL-responsive afferents was observed in rats with SCI-induced allodynia. Importantly, in SCI rats that received Ex, the incidence of tactile allodynia decreased to 7% (1/17) and there was maintenance of GDNF and artemin at normal levels, with a normal distribution of GFL-responsive fibers. These data suggest that GFLs and/or their downstream effectors may be important modulators of pain fiber plasticity, representing effective targets for anti-allodynic therapeutics. Furthermore, we highlight the potent beneficial effects of acute exercise after SCI.
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Details
- Title
- Acute exercise prevents the development of neuropathic pain and the sprouting of non-peptidergic (GDNF- and artemin-responsive) c-fibers after spinal cord injury
- Creators
- Megan Ryan Detloff - Department of Neurobiology and Anatomy, Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, PA 19129, USA. Electronic address: mdetloff@drexelmed.eduEvan J Smith - Department of Neurobiology and Anatomy, Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, PA 19129, USADaniel Quiros Molina - Department of Neurobiology and Anatomy, Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, PA 19129, USAPatrick D Ganzer - Department of Neurobiology and Anatomy, Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, PA 19129, USAJohn D Houlé - Department of Neurobiology and Anatomy, Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, PA 19129, USA
- Publication Details
- Experimental neurology, v 255, pp 38-48
- Publisher
- Elsevier; United States
- Grant note
- NS 026380 / NINDS NIH HHS R37 NS026380 / NINDS NIH HHS R01 NS026380 / NINDS NIH HHS P01 NS055976 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000335287600005
- Scopus ID
- 2-s2.0-84896299846
- Other Identifier
- 991014878413504721
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- Neurosciences