A preclinical model of hyperalgesia following spinal stenosis/compression

Vierck, Charles J.; Baastrup, Cathrine; Maersk-Moller, Camilla Charlotte; Roth, Marc; Cannon, Richard L.; Finnerup, Nanna Brix; Yezierski, Robert P.

doi:10.1002/ejp.640

Cited by 13 publications

(11 citation statements)

References 42 publications

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“…Rats with severe T3 SCI also consistently developed forelimb tactile allodynia, which was reversed by gabapentin, and increased sensitivity to cold, both of which have been reported by patients with "at-level" pain [26]. "At-level" cold allodynia has previously been reported in a model of photochemically-induced ischemic injury [27], while conscious aversion to cold flooring has been reported in a rat model of spinal stenosis [53]. Acute "at-level" cold sensitivity to acetone has also been reported following T9 complete transection [41].…”

Section: ]mentioning

confidence: 71%

Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury

Lee-Kubli

Ingves

Henry

et al. 2016

Experimental Neurology

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Human SCI is frequently associated with chronic pain that is severe and refractory to medical therapy. Most rodent models used to assess pain outcomes in SCI apply moderate injuries to lower thoracic spinal levels, whereas the majority of human lesions are severe in degree and occur at cervical or upper thoracic levels. To better model and understand mechanisms associated with chronic pain after SCI, we subjected adult rats to T3 severe compression or complete transection lesions, and examined pain-related behaviors for three months. Within one week after injury, rats developed consistent forepaw pain-related behaviors including increased spontaneous lifts, tactile allodynia and cold sensitivity that persisted for three months. Place escape avoidance testing confirmed that withdrawal of the forepaws from a von Frey stimulus represented active pain-related aversion. Spontaneous and evoked pain-related measures were attenuated by gabapentin, further indicating that these behaviors reflect development of pain. Spinal level of injury was relevant: rats with T11 severe SCI did not exhibit forepaw pain-related behaviors. Immunoblotting and immunofluorescence of C6-C8 spinal dorsal horn, reflecting sensory innervation of the forepaw, revealed: 1) expansion of CGRP immunoreactivity in lamina I/II; 2) increased GAP-43 expression; and 3) increased IBA1, GFAP and connexin-43 expression. These findings indicate that aberrant pain fiber sprouting and gliopathy occur after severe SCI. Notably, satellite glial cells (SGCs) in C6-C8 DRGs exhibited increases in GFAP and connexin-43, suggesting ongoing peripheral sensitization. Carbenoxolone, a gap junction inhibitor, and specific peptide inhibitors of connexin-43, ameliorated established tactile allodynia after severe SCI. Collectively, severe T3 SCI successfully models persistent pain states and could constitute a useful model system for examining candidate translational pain therapies after SCI.

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Section: ]mentioning

confidence: 71%

Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury

Lee-Kubli

Ingves

Henry

et al. 2016

Experimental Neurology

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“…An alternate version of the task avoids this problem by warming or cooling the entire floor in the dark side of the chamber. This variant of PEAP has shown that rats with T13 hemisection have reduced sensitivity to noxious heat [39], but those with a spinal stenosis show increased sensitivity to cold and heat [43]. However, this too can be an imperfect approach as only the paws are contact with the stimulus surface, precluding evaluation of at-level pain in the flanks.…”

Section: Evaluating Conscious Perception Of Pain In Sci Modelsmentioning

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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“…In a similar dual-chamber PEAP paradigm the mechanical stimulation is replaced by thermal stimulation to assess cold and/ or heat sensitivity [28,35]. In the dark chamber hot, cold or neutral thermal stimuli are applied through a temperature regulated floor plate.…”

Section: 1 Behavioral Assessmentsmentioning

confidence: 99%

“…In this paradigm animals are trained to establish stimulus preference between avoidance of thermal stimulation and bright light [29]. In a model of low thoracic spinal cord compression Vierck et al were able to measure cold and hot hyperalgesia in SCI [35]. …”

Section: 1 Behavioral Assessmentsmentioning

confidence: 99%

Assessments of sensory plasticity after spinal cord injury across species

Haefeli

Huie

Morioka

et al. 2017

Neuroscience Letters

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Spinal cord injury (SCI) is a multifaceted phenomenon associated with alterations in both motor function and sensory function. A majority of patients with SCI report sensory disturbances, including not only loss of sensation, but in many cases enhanced abnormal sensation, dysesthesia and pain. Development of therapeutics to treat these abnormal sensory changes require common measurement tools that can enable cross-species translation from animal models to human patients. We review the current literature on translational nociception/pain measurement in SCI and discuss areas for further development. Although a number of tools exist for measuring both segmental and affective sensory changes, we conclude that there is a pressing need for better, integrative measurement of nociception/pain outcomes across species to enhance precise therapeutic innovation for sensory dysfunction in SCI.

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A preclinical model of hyperalgesia following spinal stenosis/compression

Abstract: Histology revealed that hyperalgesia occurred when there was: (1) damage to spinal white matter; or (2) cystic cavitation; or (3) compression and distortion of the spinal cord without an obvious loss of grey or white matter.

Cited by 13 publications

References 42 publications

Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury

Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury

Neuropathic Pain After Spinal Cord Injury: Challenges and Research Perspectives

Assessments of sensory plasticity after spinal cord injury across species

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