Heterogeneity in patterns of pain development after nerve injury in rats and the influence of sex

Sherman, Katherine; Woyach, Victoria; Eisenach, James C.; Hopp, Francis A.; Cao, Freddy; Hogan, Quinn H.; Dean, Caron

doi:10.1016/j.ynpai.2021.100069

Cited by 5 publications

(2 citation statements)

References 80 publications

(125 reference statements)

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“…2I). This suggests the temporal impact of SNI differs between males and females, in line with what others have seen in other behavioral paradigms 6,[17][18][19] . Importantly, this was the only sex difference we found throughout this entire study.…”

Section: Sni Decreases the Distance Between The Injured Limb And Body...supporting

confidence: 88%

Spared nerve injury causes motor phenotypes unrelated to pain in mice

Norris

Dunn

Aravamuthan³

et al. 2023

Preprint

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Most animal models of neuropathic pain use targeted nerve injuries quantified with motor reflexive measures in response to an applied noxious stimulus. These motor reflexive measures can only accurately represent a pain response if motor function in also intact. The commonly used spared nerve injury (SNI) model, however, damages the tibial and common peroneal nerves that should result in motor phenotypes (i.e., an immobile or "flail" foot) not typically captured in sensory assays. To test the extent of these issues, we used DeepLabCut, a deep learning-based markerless pose estimation tool to quantify spontaneous limb position in C57BL/6J mice during tail suspension following either SNI or sham surgery. Using this granular detail, we identified the expected flail foot-like impairment, but we also found SNI mice hold their injured limb closer to the body midline compared to shams. These phenotypes were not present in the Complete Freunds Adjuvant model of inflammatory pain and were not reversed by multiple analgesics with different mechanisms of action, suggesting these SNI-specific phenotypes are not directly related to pain. Together these results suggest SNI causes previously undescribed phenotypes unrelated to altered sensation that are likely underappreciated while interpreting preclinical pain research outcomes.

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Section: Sni Decreases the Distance Between The Injured Limb And Body...supporting

confidence: 88%

Spared nerve injury causes motor phenotypes unrelated to pain in mice

Norris

Dunn

Aravamuthan³

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…In addition to the changes in the plantar and dorsal mechanical sensitivity, all injured animals displayed spinal mechanical allodynia within the receptive fields at the level of injury and well below. Large interindividual variability in pain patterns has already been reported in different preclinical models of injury-related pain, with attempts to classify nociceptive variability (non-sex-dependent) in rats [ 50 , 51 , 52 ]. Despite the great scientific interest and a large number of observations of pain heterogeneity between individual animals with similar injury etiology, including changes between the contralateral and ipsilateral sensory abnormalities, the mechanistic basis of such heterogeneity remains unexplored.…”

Section: Discussionmentioning

confidence: 99%

Phenotypes of Motor Deficit and Pain after Experimental Spinal Cord Injury

et al. 2022

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Motor disability is a common outcome of spinal cord injury (SCI). The recovery of motor function after injury depends on the severity of neurotrauma; motor deficit can be reversible, at least partially, due to the innate tissue capability to recover, which, however, deteriorates with age. Pain is often a comorbidity of injury, although its prediction remains poor. It is largely unknown whether pain can attend motor dysfunction. Here, we implemented SCI for modelling severe and moderate neurotrauma and monitored SCI rats for up to 5 months post-injury to determine the profiles of both motor deficit and nociceptive sensitivity. Our data showed that motor dysfunction remained persistent after a moderate SCI in older animals (5-month-old); however, there were two populations among young SCI rats (1 month-old) whose motor deficit either declined or exacerbated even more over 4–5 weeks after identical injury. All young SCI rats displayed changed nociceptive sensitivity in thermal and mechanical modalities. The regression analysis of the changes revealed a population trend with respect to hyper- or hyposensitivity/motor deficit. Together, our data describe the phenotypes of motor deficit and pain, the two severe complications of neurotrauma. Our findings also suggest the predictability of motor dysfunction and pain syndromes following SCI that can be a hallmark for long-term rehabilitation and recovery after injury.

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