Journal article
Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats
Experimental neurology, v 212(2), pp 337-347
01 Aug 2008
PMID: 18511041
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Spinal cord injury (SCI) impairs sensory systems causing chronic allodynia. Mechanisms underlying neuropathic pain have been more extensively studied following peripheral nerve injury (PNI) than after central trauma. Microglial activation, pro-inflammatory cytokine production and activation of p38 MAP kinase pathways may induce at-level allodynia following PNI. We investigated whether midthoracic SCI elicits similar behavioral and cellular responses below the level of injury (lumbar spinal cord; L5). Importantly, we show that anatomical connections between L5 and supraspinal centers remain intact after moderate SCI allowing direct comparison to a well-established model of peripheral nerve injury. We found that SCI elicits below-level allodynia of similar magnitude to at-level pain caused by a peripheral nerve injury. Moreover, the presence of robust microglial activation in L5 cord predicted allodynia in 86% of rats. Also increased phosphorylation of p38 MAP kinase occurred in the L5 dorsal horn of allodynic rats. For below-level allodynia after SCI, TNF-alpha and IL-1 beta increased in the L5 dorsal horn by 7 dpo and returned to baseline by 35 dpo. Interestingly, IL-6 remains at normal levels early after SCI and increases at chronic time points. Increased levels of pro-inflammatory cytokines also occurred in the thalamus after SCI-induced allodynia. These data suggest that remote microglial activation is pivotal in the development and maintenance of below-level allodynia after SCI. Fractalkine, a known activator of microglia, and astrocytes were not primary modulators of below-level pain. Although the mechanisms of remote microglial activation are unknown, this response may be a viable target for limiting or preventing neuropathic pain after SCI in humans. (C) 2008 Elsevier Inc. All rights reserved.
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Details
- Title
- Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats
- Creators
- Megan Ryan Detloff - The Ohio State UniversityLesley C. Fisher - The Ohio State UniversityVioletta McGaughy - The Ohio State UniversityErin E. Longbrake - The Ohio State UniversityPhillip G. Popovich - The Ohio State UniversityD. Michele Basso - The Ohio State University
- Publication Details
- Experimental neurology, v 212(2), pp 337-347
- Publisher
- Elsevier
- Number of pages
- 11
- Grant note
- R01 NS037846; P30 NS045758; R01 NS043798-01; R01 NS043798-05S1; F31 NS058138; P30-NS045758; R01 NS043798; NS37846; NS43798 / NINDS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R01NS037846 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Web of Science ID
- WOS:000258252000016
- Scopus ID
- 2-s2.0-47349092661
- Other Identifier
- 991020099666404721
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- Neurosciences