Thermal hyperalgesia and dynamic weight bearing share similar recovery dynamics in a sciatic nerve entrapment injury model

Sheehan, Garrett D.; Martin, Molly K.; Young, Violet A.; Powell, Rasheen; Bhattacharjee, Abhishek

doi:10.1016/j.ynpai.2021.100079

Cited by 10 publications

(11 citation statements)

References 40 publications

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“…Changes in weight bearing on each hindpaw were individually calculated as a percent of total body weight, and the data indicate that shifts in hindpaw weight bearing after SNI were driven by distinct changes in behavior in male and female mice. Male mice primarily increased weight bearing on the contralateral hindpaw after surgery, similar to previous reports (Blaszczyk et al, 2018; Sheehan et al, 2021). In contrast, female mice decreased weight bearing on the ipsilateral paw.…”

Section: Discussionsupporting

confidence: 90%

“…In the spinal nerve ligation model, decreases in ipsilateral hindpaw and increases in contralateral hindpaw weight were reported (Blaszczyk et al, 2018). In a model of sciatic nerve cuff injury model that induces hyperalgesia that later resolves, shifts in weight bearing were temporally correlated with hyperalgesia (Sheehan et al, 2021), potentially consistent with the current findings of reversal of mechanical hypersensitivity altered weight bearing by EtOH in the SNI model. While it may be difficult to disentangle changes in DWB due to injury and changes in DWB due to hypersensitivity caused by injury, DWB captures aspects of the pain experience that are not captured with von Frey.…”

Section: Discussionsupporting

confidence: 81%

“…Sheehan et al, 2021), potentially consistent with the current findings of reversal of mechanical hypersensitivity altered weight bearing by EtOH in the SNI model. While it may be difficult to disentangle changes in DWB due to injury and changes in DWB due to hypersensitivity caused by injury, DWB captures aspects of the pain experience that are not captured with von Frey.…”

supporting

confidence: 91%

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Effects of ethanol on mechanical allodynia and dynamic weight bearing in male and female mice with spared nerve injury

Nothem

Wickman

Giacometti

et al. 2022

Alcohol: Clinical and Experimental Research

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Background Men and women with chronic pain report increased alcohol use and are more likely to be diagnosed with alcohol use disorder. The relationship between alcohol use and pain is bidirectional. Alcohol is used as an analgesic, but chronic alcohol intake increases pain. Sex differences in the relationship between chronic pain and alcohol are reported in the clinical and preclinical literature, but due to this bidirectional relationship, it is challenging to investigate the mechanisms that contribute to these differences. Thus, animal models of chronic pain are needed to characterize the efficacy of ethanol as an analgesic in males and females. The current experiments tested the hypothesis that ethanol differentially reduces pain behaviors in male and female mice in chronic neuropathic pain. Methods The spared nerve injury (SNI) model was used to investigate the analgesic effects of multiple doses of ethanol (0.5, 1, 2, g/kg i.p.) in male and female mice using von Frey and dynamic weight‐bearing (DWB) assays. Results In both male and female mice, SNI led to robust allodynia and shifts in dynamic weight bearing. In male SNI mice, all three doses of ethanol fully reversed mechanical allodynia and shifts in DWB. In SNI females, only the highest dose (2.0 g/kg) was fully antiallodynic in the von Frey assay, while shifts in weight bearing were reversed at the 1.0 and 2.0 g/kg doses. The differences between male and females were not due to lower blood ethanol concentrations in female mice. Conclusion These data indicate that while ethanol has antiallodynic and antinociceptive effects in male and female mice, the doses and time course of these effects are distinct. Studies investigating the relationship between pain and ethanol exposure in mice should consider sex as a key variable. These data also inform reported sex differences in rodent models of chronic pain and in chronic pain patients.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 81%

supporting

confidence: 91%

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Effects of ethanol on mechanical allodynia and dynamic weight bearing in male and female mice with spared nerve injury

Nothem

Wickman

Giacometti

et al. 2022

Alcohol: Clinical and Experimental Research

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“…Using mechanical withdrawal testing, a test of both A delta and C fibers,20 26 FUS application increased the withdrawal threshold for 2 weeks compared with controls. However, with thermal withdrawal testing, primarily a test of C fiber nociception,21 27 FUS application increased the withdrawal threshold compared with controls for the duration of this study, 4 weeks. After FUS application, HP flexion was also decreased considerably for approximately 1.5–2 weeks.…”

Section: Discussionmentioning

confidence: 70%

Focused ultrasound-induced inhibition of peripheral nerve fibers in an animal model of acute pain

Anderson

Pacharinsak

Vilches-Moure

et al. 2023

Reg Anesth Pain Med

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BackgroundModerate-to-severe acute pain is prevalent in many healthcare settings and associated with adverse outcomes. Peripheral nerve blockade using traditional needle-based and local anesthetic-based techniques improves pain outcomes for some patient populations but has shortcomings limiting use. These limitations include its invasiveness, potential for local anesthetic systemic toxicity, risk of infection with an indwelling catheter, and relatively short duration of blockade compared with the period of pain after major injuries. Focused ultrasound is capable of inhibiting the peripheral nervous system and has potential as a pain management tool. However, investigations of its effect on peripheral nerve nociceptive fibers in animal models of acute pain are lacking. In an in vivo acute pain model, we investigated focused ultrasound’s effects on behavior and peripheral nerve structure.MethodsFocused ultrasound was applied directly to the sciatic nerve of rats just prior to a hindpaw incision; three control groups (focused ultrasound sham only, hindpaw incision only, focused ultrasound sham+hindpaw incision) were also included. For all four groups (intervention and controls), behavioral testing (thermal and mechanical hyperalgesia, hindpaw extension and flexion) took place for 4 weeks. Structural changes to peripheral nerves of non-focused ultrasound controls and after focused ultrasound application were assessed on days 0 and 14 using light microscopy and transmission electron microscopy.ResultsCompared with controls, after focused ultrasound application, animals had (1) increased mechanical nociceptive thresholds for 2 weeks; (2) sustained increase in thermal nociceptive thresholds for ≥4 weeks; (3) a decrease in hindpaw motor response for 0.5 weeks; and (4) a decrease in hindpaw plantar sensation for 2 weeks. At 14 days after focused ultrasound application, alterations to myelin sheaths and nerve fiber ultrastructure were observed both by light and electron microscopy.DiscussionFocused ultrasound, using a distinct parameter set, reversibly inhibits A-delta peripheral nerve nociceptive, motor, and non-nociceptive sensory fiber-mediated behaviors, has a prolonged effect on C nociceptive fiber-mediated behavior, and alters nerve structure. Focused ultrasound may have potential as a peripheral nerve blockade technique for acute pain management. However, further investigation is required to determine C fiber inhibition duration and the significance of nerve structural changes.

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“…Chronic constriction injury of the sciatic nerve is a widely used peripheral nerve entrapment animal model of neuropathic pain, which involves partial nerve injury [21]. In this study, a rat CCI model was chosen to explore the effect of perineural injection of BoNT/A in the treatment of peripheral nerve injury inducedneuropathic pain, aimed at providing a suitable administration method of BoNT/A for clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats

Wei²,

Wu³

et al. 2023

Neurochem Res

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This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 in ammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery.Moreover, C-ber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroin ammation and synaptic plasticity in spinal dorsal horn of each group was examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were signi cantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral mechanisms of perineural injection of BoNT/A may be related to the protective effect on myelin sheath by inhibiting NLRP3 in ammasome and promoting autophagy ow, while the central mechanisms may be associated with inhibition of neuroin ammation and synaptic plasticity in spinal dorsal horn due to its ability to inhibit SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central mechanisms.

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Thermal hyperalgesia and dynamic weight bearing share similar recovery dynamics in a sciatic nerve entrapment injury model

Cited by 10 publications

References 40 publications

Effects of ethanol on mechanical allodynia and dynamic weight bearing in male and female mice with spared nerve injury

Effects of ethanol on mechanical allodynia and dynamic weight bearing in male and female mice with spared nerve injury

Focused ultrasound-induced inhibition of peripheral nerve fibers in an animal model of acute pain

Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats

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