Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury

Gaudet, Andrew D.; Ayala, Monica T.; Schleicher, Wolfgang E.; Smith, Elana J.; Bateman, Emily; Maier, Steven F.; Watkins, Linda R.

doi:10.1016/j.expneurol.2017.05.011

Cited by 47 publications

(56 citation statements)

References 71 publications

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“…Additional tests for mechanical (von Frey) and thermal (hot water tail-flick) hypersensitivity showed that naïve and sham conditions did not differ significantly at any time point (Figures 1B1,B2). Previous literature has demonstrated analogous results when testing hindpaw thermal sensitivity by radiant heat stimulus on sham animals at multiple time points (Christensen and Hulsebosch, 1997;Bedi et al, 2010;Gaudet et al, 2017). We did not examine SCI mice for thermal or mechanical sensitivity, as paralysis below the level of injury prohibited below-level sensitivity testing at the time points studied.…”

Section: Characterization Of Behavioral and Inflammatory Phenotypes Omentioning

confidence: 90%

“…The development of chronic pain at later time points following clip-compression models of SCI (in addition to several other models) has already been well characterized. Therefore, we focused on early time points after injury, to identify contributions to the onset of pain, rather than changes after chronic pain has already developed (Bruce et al, 2002;Nakae et al, 2011;Gaudet et al, 2017).…”

Section: Characterization Of Behavioral and Inflammatory Phenotypes Omentioning

confidence: 99%

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Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes

Yasko

Moss

Mains

2019

Front. Mol. Neurosci.

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Traumatic spinal cord injury (SCI) has devastating implications for patients, including a high predisposition for developing chronic pain distal to the site of injury. Chronic pain develops weeks to months after injury, consequently, patients are treated after irreparable changes have occurred. Nociceptors are central to chronic pain; however, the diversity of this cellular population presents challenges to understanding mechanisms and attributing pain modalities to specific cell types. To begin to address how peripheral sensory neurons below the injury level may contribute to the below-level pain reported by SCI patients, we examined SCI-induced changes in gene expression in lumbar dorsal root ganglia (DRG) below the site of injury. SCI was performed at the T10 vertebral level, with injury produced by a vessel clip with a closing pressure of 15 g for 1 min. Alterations in gene expression produce long-term sensory changes, therefore, we were interested in studying SCI-induced transcripts before the onset of chronic pain, which may trigger changes in downstream signaling pathways and ultimately facilitate the transmission of pain. To examine changes in the nociceptor subpopulation in DRG distal to the site of injury, we retrograde labeled sensory neurons projecting to the hairy hindpaw skin with fluorescent dye and collected the corresponding lumbar (L2-L6) DRG 4 days post-injury. Following dissociation, labeled neurons were purified by fluorescenceactivated cell sorting (FACS). RNA was extracted from sorted sensory neurons of naïve, sham, or SCI mice and sequenced. Transcript abundances validated that the desired population of nociceptors were isolated. Cross-comparisons to data sets from similar studies confirmed, we were able to isolate our cells of interest and identify a unique pattern of gene expression within a subpopulation of neurons projecting to the hairy hindpaw skin. Differential gene expression analysis showed high expression levels and significant transcript changes 4 days post-injury in SCI cell populations relevant to the onset of chronic pain. Regulatory interrelationships predicted by pathway analysis implicated changes within the synaptogenesis signaling pathway as well as networks related to inflammatory signaling mechanisms, suggesting a role for synaptic plasticity and a correlation with pro-inflammatory signaling in the transition from acute to chronic pain.

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Section: Characterization Of Behavioral and Inflammatory Phenotypes Omentioning

confidence: 90%

Section: Characterization Of Behavioral and Inflammatory Phenotypes Omentioning

confidence: 99%

Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes

Yasko

Moss

Mains

2019

Front. Mol. Neurosci.

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“…Only a few studies have evaluated experimental SCI pain in both male and female subjects. Following contusion injury, male rats have a greater reduction in hindlimb mechanical withdrawal thresholds than females, though rats of both sexes develop increased responsiveness to thermal stimuli [216]. However, operant testing in a model of quisqualate injection that causes excitotoxic SCI suggests that female rats have more thermal hyperalgesia and less cold hyperalgesia than their male counterparts [217].…”

Section: Mechanisms Of Pain In Male Versus Female Sci Painmentioning

confidence: 99%

Neuropathic Pain After Spinal Cord Injury: Challenges and Research Perspectives

2018

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Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that remains difficult to treat because underlying mechanisms are not yet fully understood. In part, this is due to limitations of evaluating neuropathic pain in animal models in general, and SCI rodents in particular. Though pain in patients is primarily spontaneous, with relatively few patients experiencing evoked pains, animal models of SCI pain have primarily relied upon evoked withdrawals. Greater use of operant tasks for evaluation of the affective dimension of pain in rodents is needed, but these tests have their own limitations such that additional studies of the relationship between evoked withdrawals and operant outcomes are recommended. In preclinical SCI models, enhanced reflex withdrawal or pain responses can arise from pathological changes that occur at any point along the sensory neuraxis. Use of quantitative sensory testing for identification of optimal treatment approach may yield improved identification of treatment options and clinical trial design. Additionally, a better understanding of the differences between mechanisms contributing to at- versus below-level neuropathic pain and neuropathic pain versus spasticity may shed insights into novel treatment options. Finally, the role of patient characteristics such as age and sex in pathogenesis of neuropathic SCI pain remains to be addressed.

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“…The PI also participates in the maintenance of persistent pain [28] and is implicated in the process of chronic pain [29]. However, earlier studies about the role of insular subareas in the regulation of pain have mainly focused on healthy controls (HCs) or rodent animals [10,11,30], and few studies have paid attention to the functions of insula subregion in the pathological pain. Considering the high prevalence of NP secondary to SCI and the insular susceptibility and heterogeneity in NP state, it is essential to reveal the reorganization of the insular subareas in incomplete SCI (ISCI) patients with NP.…”

Section: Introductionmentioning

confidence: 99%

The Reorganization of Insular Subregions in Individuals with Below-Level Neuropathic Pain following Incomplete Spinal Cord Injury

Chen

et al. 2020

Neural Plasticity

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Objective. To investigate the reorganization of insular subregions in individuals suffering from neuropathic pain (NP) after incomplete spinal cord injury (ISCI) and further to disclose the underlying mechanism of NP. Method. The 3D high-resolution T1-weighted structural images and resting-state functional magnetic resonance imaging (rs-fMRI) of all individuals were obtained using a 3.0 Tesla MRI system. A comparative analysis of structure and function connectivity (FC) with insular subareas as seeds in 10 ISCI individuals with below-level NP (ISCI-P), 11 ISCI individuals without NP (ISCI-N), and 25 healthy controls (HCs) was conducted. Associations between the structural and functional alteration of insula subregions and visual analog scale (VAS) scores were analyzed using the Pearson correlation in SPSS 20. Results. Compared with ISCI-N patients, when the left posterior insula as the seed, ISCI-P showed increased FC in right cerebellum VIIb and cerebellum VIII, Brodmann 37 (BA 37). When the left ventral anterior insula as the seed, ISCI-P indicated enhanced FC in right BA18 compared with ISCI-N patients. These increased FCs positively correlated with VAS scores. Relative to HCs, ISCI-P presented increased FC in the left hippocampus when the left dorsal anterior insula was determined as the seed. There was no statistical difference in the volume of insula subregions among the three groups. Conclusion. Our study indicated that distinctive patterns of FC in each subregion of insula suggest that the insular subareas participate in the NP processing through different FC following ISCI. Further, insula subregions could serve as a therapeutic target for NP following ISCI.

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Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury

Cited by 47 publications

References 71 publications

Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes

Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes

Neuropathic Pain After Spinal Cord Injury: Challenges and Research Perspectives

The Reorganization of Insular Subregions in Individuals with Below-Level Neuropathic Pain following Incomplete Spinal Cord Injury

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