Validity of acute and chronic tactile sensory testing after spinal cord injury in rats

Detloff, Megan Ryan; Clark, Leslie M.; Hutchinson, Kenneth D.; Kloos, Anne; Fisher, Lesley C.; Basso, D. Michele

doi:10.1016/j.expneurol.2010.07.009

Cited by 64 publications

(52 citation statements)

References 97 publications

(152 reference statements)

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“…This has important implications for the interpretation of most preclinical rodent SCI pain studies, as pain actually was not studied. [4][5][6] Furthermore, the AL-ER test revealed forceful bilateral hindpaw motor ability (kicking/jumping) upon modest sensory stimulation of a single hindpaw, even when SCI animals were still unable to support their bodyweight during locomotion. The latter is in line with observations that complex BL-WR can also be evoked in complete spinal cord-transected animals, even within hours after injury.…”

Section: Discussionmentioning

confidence: 99%

“…4,14 Figure 1 Schematic of above-level escape response (AL-ER) testing upon below-level stimulation. Shown is the way in which the animals were held for the AL-ER testing upon hindpaw stimulation with a mechanical (black arrow, dorsal) or a thermal (gray arrow, plantar) stimulus.…”

Section: Sensory Testingmentioning

confidence: 99%

“…2, 3 In animal SCI pain models, pain is often investigated by determining hypersensitivity, as is mostly done in dermatomes below the level of injury. [4][5][6] Changes in below-level responses occur almost immediately after rodent SCI and remain for months. 7 Typically, a decreased hindpaw withdrawal threshold to stimuli is observed and considered to reflect a central neuropathic below-level chronic pain state.…”

Section: Introductionmentioning

confidence: 99%

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Translation of the rat thoracic contusion model; part 1—supraspinally versus spinally mediated pain-like responses and spasticity

et al. 2014

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Study design: Experimental animal study. Objectives: Stimulus-evoked below-level paw withdrawals in animal models of spinal cord injury (SCI) can be mediated solely by below-level spinal cord reflexes. Interpreting lowered thresholds for such responses as a model for chronic below-level pain after (thoracic contusion) SCI appears not appropriate, which requires reinterpretation of many prior results. However, how to reinterpret the changes in withdrawal thresholds and what can be a better alternative for pain/sensory assessments remains unclear. Setting: University of California, San Diego. Methods: We introduce a method using supraspinally mediated escape responses to assess pain-like sensitivity thresholds on a continuous/linear scale. To further understand the decrease in hindpaw withdrawal thresholds, we investigated whether they may be interpreted as spasticity. Results: The escape response test can be used to assess SCI-induced changes in below-level sensory thresholds. These thresholds were found to increase soon after moderate or severe SCI, while, in parallel, hindpaw withdrawal thresholds decreased. However, the latter did not co-occur with spasticity, suggesting that SCI-induced increased withdrawal responses are probably best interpreted as a form of hyperreflexia with pathophysiological analogies of spasms and/or clonus, or a species-specific phenomenon. Conclusion: Decreased below-level withdrawal thresholds do not reflect pain-like hypersensitivity in rodent models of (thoracic contusion) SCI. A large body of previous preclinical SCI pain research needs reinterpretation. We actually found below-level thermal and mechanical hypoesthesia and we also excluded a relation between withdrawal hyperreflexia and spasticity. Withdrawal hyperreflexia might still prove useful to model spasms or clonus, which are, like hypoesthesia, also significant clinical problems after SCI.

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Section: Discussionmentioning

confidence: 99%

Section: Sensory Testingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Translation of the rat thoracic contusion model; part 1—supraspinally versus spinally mediated pain-like responses and spasticity

et al. 2014

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“…The up-down method for von Frey hair monofilaments (VFH, Stoelting Co., Wood Dale, IL) was used to measure the degree of tactile sensory changes after SCI. 15,16 Post-injury assessment of nocifensive behavior was initiated only when there was evidence of weight support for a given limb. This ensured that the rat had suitable motor control to remove the paw from an unpleasant stimulus.…”

Section: Behavioral Measuresmentioning

confidence: 99%

“…Rodent SCI models of neuropathic pain are attractive because they directly emulate the human condition, and it has been established that sensitive, accurate, and valid measures of evoked tactile and thermal sensation can be obtained throughout the period of recovery. 6,15,16 After incomplete SCI, hypersensitive nocifensive behaviors correspond to anatomical and electrophysiological changes in supraspinal regions such as the ventral posterio-lateral (VPL) nucleus of the thalamus and the cortex, [17][18][19] indicating that evoked stimulation is associated with supraspinal awareness and perception.…”

mentioning

confidence: 99%

Chronic At- and Below-Level Pain after Moderate Unilateral Cervical Spinal Cord Contusion in Rats

Detloff

Wade

Houlé

2013

Journal of Neurotrauma

Self Cite

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Chronic neuropathic pain is a significant consequence of spinal cord injury (SCI) that is associated with evoked pain, including allodynia and/or hyperalgesia. Allodynia is defined as a painful response to normally innocuous stimuli, and hyperalgesia occurs when there is an amplified pain response to normally noxious stimuli. We describe a model of a unilateral cervical level (C5) contusion injury where sensory recovery was assessed weekly for 6 weeks in 32 adult, female, Sprague-Dawley rats. Bilateral thermal hyperalgesia and tactile allodynia are detectable in the fore-and hindpaws as early as 7 days post-injury (dpi) and persist for at least 42 days. Paw withdrawal latency in response to a noxious thermal stimulus significantly intra-animal pre-operative values. Change in paw withdrawal latency plateaued at 21 dpi. Interestingly, bilateral forepaw allodynia develops in fewer than 40% of rats as measured by von Frey monofilament testing. Similar results occur in the hindpaws, where bilateral allodynia occurs in 46% of rats with SCI. The contralesional forepaw and both hindpaws of rats showed a slight increase in paw withdrawal threshold to tactile stimuli acutely after SCI, corresponding to ipsilesional forelimb motor deficits that resolve over time. That there is no difference among allodynic and non-allodynic groups in overall spared tissue or specifically of the dorsal column or ventrolateral white matter where ascending sensory tracts reside suggests that SCI-induced pain does not depend solely on the size or extent of the lesion, but that other mechanisms are in play. These observations provide a valid model system for future testing of therapeutic interventions to prevent the onset or to reduce the debilitating effects of chronic neuropathic pain after SCI.

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Prevascularized Scaffolds Bearing Human Dental Pulp Stem Cells for Treating Complete Spinal Cord Injury

Guo

Redenski

Landau

et al. 2020

Adv Healthcare Materials

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The regeneration of injured spinal cord is hampered by the lack of vascular supply and neurotrophic support. Transplanting tissue-engineered constructs with developed vascular networks and neurotrophic factors, and further understanding the pattern of vessel growth in the remodeled spinal cord tissue are greatly desired. To this end, highly vascularized scaffolds embedded with human dental pulp stem cells (DPSCs) are fabricated, which possess paracrine-mediated angiogenic and neuroregenerative potentials. The potent pro-angiogenic effect of the prevascularized scaffolds is first demonstrated in a rat femoral bundle model, showing robust vessel growth and blood perfusion induced within these scaffolds postimplantation, as evidenced by laser speckle contrast imaging and 3D microCT dual imaging modalities. More importantly, in a rat complete spinal cord transection model, the implantation of these scaffolds to the injured spinal cords can also promote revascularization, as well as axon regeneration, myelin deposition, and sensory recovery. Furthermore, 3D microCT imaging and novel morphometric analysis on the remodeled spinal cord tissue demonstrate substantial regenerated vessels, more significantly in the sensory tract regions, which correlates with behavioral recovery following prevascularization treatment. Taken together, prevascularized DPSC-embedded constructs bear angiogenic and neurotrophic potentials, capable of augmenting and modulating SCI repair.

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Validity of acute and chronic tactile sensory testing after spinal cord injury in rats

Cited by 64 publications

References 97 publications

Translation of the rat thoracic contusion model; part 1—supraspinally versus spinally mediated pain-like responses and spasticity

Translation of the rat thoracic contusion model; part 1—supraspinally versus spinally mediated pain-like responses and spasticity

Chronic At- and Below-Level Pain after Moderate Unilateral Cervical Spinal Cord Contusion in Rats

Prevascularized Scaffolds Bearing Human Dental Pulp Stem Cells for Treating Complete Spinal Cord Injury

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