Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats

Kandasamy, Ram; Lee, Andrea T.; Morgan, Michael M.

doi:10.1186/s10194-017-0721-6

Cited by 39 publications

(33 citation statements)

References 32 publications

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“…Since then, a range of other pain conditions have been shown to depress wheel running in rats and mice. These include hindpaw inflammation, arthritis, migraine-like pain, neuropathic pain, surgical pain, and more (Cattaruzza et al, 2013;Kandasamy et al, 2016Kandasamy et al, , 2017bKendall et al, 2016;Pitzer et al, 2016aPitzer et al, , 2016bStevenson et al, 2011;Tang et al, 2016;Whitehead et al, 2017).…”

Section: Wheel Runningmentioning

confidence: 99%

Pros and Cons of Clinically Relevant Methods to Assess Pain in Rodents

Tappe‐Theodor

King

Morgan

2019

Neuroscience & Biobehavioral Reviews

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130

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The primary objective of preclinical pain research is to improve the treatment of pain. Decades of research using pain-evoked tests has revealed much about mechanisms but failed to deliver new treatments. Evoked pain-tests are often limited because they ignore spontaneous pain and motor or disruptive side effects confound interpretation of results. New tests have been developed to focus more closely on clinical goals such as reducing pathological pain and restoring function. The objective of this review is to describe and discuss several of these tests. We focus on: Grimace Scale, Operant Behavior, Wheel Running, Burrowing, Nesting, Home Cage Monitoring, Gait Analysis and Conditioned Place Preference/ Aversion. A brief description of each method is presented along with an analysis of the advantages and limitations. The pros and cons of each test will help researchers identify the assessment tool most appropriate to meet their particular objective to assess pain in rodents. These tests provide another tool to unravel the mechanisms underlying chronic pain and help overcome the translational gap in drug development.

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Section: Wheel Runningmentioning

confidence: 99%

Pros and Cons of Clinically Relevant Methods to Assess Pain in Rodents

Tappe‐Theodor

King

Morgan

2019

Neuroscience & Biobehavioral Reviews

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130

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“…The thermo-TRP ankyrin type-1 (TRPA1) channels - sensors of oxidative, nitrative and electrophilic stress – have been involved in different models of pain diseases [ 2 ] and seem to play a key role also in the mechanisms of migraine pain. Indeed, their activation is operated by a plethora of exogenous and endogenous stimuli, among which there are many migraine triggers [ 1 , 3 , 4 ]. TRPA1 channels can be found in many types of cells and tissue, but they are mostly expressed in sensory neurons [ 5 , 6 ]; they are implicated in meningeal nociceptive and vascular responses involving neurogenic dural vasodilatation and plasma extravasation.…”

Section: Introductionmentioning

confidence: 99%

The role of the transient receptor potential ankyrin type-1 (TRPA1) channel in migraine pain: evaluation in an animal model

et al. 2017

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BackgroundClinical and experimental studies have pointed to the possible involvement of the transient receptor potential ankyrin type-1 (TRPA1) channels in migraine pain. In this study, we aimed to further investigate the role of these channels in an animal model of migraine using a novel TRPA1 antagonist, ADM_12, as a probe.MethodsThe effects of ADM_12 on nitroglycerin-induced hyperalgesia at the trigeminal level were investigated in male rats using the quantification of nocifensive behavior in the orofacial formalin test. The expression levels of the genes coding for c-Fos, TRPA1, calcitonin gene-related peptide (CGRP) and substance P (SP) in peripheral and central areas relevant for migraine pain were analyzed. CGRP and SP protein immunoreactivity was also evaluated in trigeminal nucleus caudalis (TNC).ResultsIn rats bearing nitroglycerin-induced hyperalgesia, ADM_12 showed an anti-hyperalgesic effect in the second phase of the orofacial formalin test. This effect was associated to a significant inhibition of nitroglycerin-induced increase in c-Fos, TRPA1 and neuropeptides mRNA levels in medulla-pons area, in the cervical spinal cord and in the trigeminal ganglion. No differences between groups were seen as regards CGRP and SP protein expression in the TNC.ConclusionsThese findings support a critical involvement of TRPA1 channels in the pathophysiology of migraine, and show their active role in counteracting hyperalgesia at the trigeminal level.

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“…We have previously shown that home cage wheel running provides an objective and clinically relevant measure of the duration and magnitude of pain in rats (Kandasamy et al, 2016; 2017a; 2017b). If depression of home cage wheel running is a measure of an abnormal physiological state as these previous studies indicate, then spontaneous opioid withdrawal should also cause depression of home cage wheel running.…”

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confidence: 99%

Depression of home cage wheel running is an objective measure of spontaneous morphine withdrawal in rats with and without persistent pain

Kandasamy

Lee

Morgan

2017

Pharmacology Biochemistry and Behavior

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Opioid withdrawal in humans is often subtle and almost always spontaneous. In contrast, most preclinical studies precipitate withdrawal by administration of an opioid receptor antagonist such as naloxone. These animal studies rely on measurement of physiological symptoms (e.g., wet dog shakes) in the period immediately following naloxone administration. To more closely model the human condition, we tested the hypothesis that depression of home cage wheel running will provide an objective method to measure the magnitude and duration of spontaneous morphine withdrawal. Rats were allowed access to a running wheel in their home cage for 8 days prior to implantation of two 75 mg morphine or placebo pellets. The pellets were removed 3 or 5 days later to induce spontaneous withdrawal. In normal pain-free rats, removal of the morphine pellets depressed wheel running for 48 hours compared to rats that had placebo pellets removed. Morphine withdrawal-induced depression of wheel running was greatly enhanced in rats with persistent inflammatory pain induced by injection of Complete Freund’s Adjuvant (CFA) into the hindpaw. Removal of the morphine pellets following 3 days of treatment depressed wheel running in these rats for over 6 days. These data demonstrate that home cage wheel running provides an objective and more clinically relevant method to assess spontaneous morphine withdrawal compared to precipitated withdrawal in laboratory rats. Moreover, the enhanced withdrawal in rats with persistent inflammatory pain suggests that pain patients may be especially susceptible to opioid withdrawal.

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Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats

Cited by 39 publications

References 32 publications

Pros and Cons of Clinically Relevant Methods to Assess Pain in Rodents

Pros and Cons of Clinically Relevant Methods to Assess Pain in Rodents

The role of the transient receptor potential ankyrin type-1 (TRPA1) channel in migraine pain: evaluation in an animal model

Depression of home cage wheel running is an objective measure of spontaneous morphine withdrawal in rats with and without persistent pain

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