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Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats.

ABSTRACT: The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior.The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats.Injection of Complete Freund's Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in male and female rats. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test).Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception.The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men.

SUBMITTER: Kandasamy R

PROVIDER: S-EPMC4801754 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats.

Kandasamy Ram R Calsbeek Jonas J JJ Morgan Michael M MM

Journal of neuroscience methods 20160215

<h4>Background</h4>The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior.<h4>New method</h4>The present study evaluates home cage wheel running as an objective method to assess the ...[more]

PMID: 26891874

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Project description:Deficits in motor function are debilitating features in disorders affecting neurological, neuromuscular and musculoskeletal systems. Although these disorders can vary greatly with respect to age of onset, symptomatic presentation, rate of progression and severity, the study of these disease models in mice is confined to the use of a small number of tests, most commonly the rotarod test. To expand the repertoire of meaningful motor function tests in mice, we tested, optimised and validated an automated home-cage-based running-wheel system, incorporating a conventional wheel with evenly spaced rungs and a complex wheel with particular rungs absent. The system enables automated assessment of motor function without handler interference, which is desirable in longitudinal studies involving continuous monitoring of motor performance. In baseline studies at two test centres, consistently significant differences in performance on both wheels were detectable among four commonly used inbred strains. As further validation, we studied performance in mutant models of progressive neurodegenerative diseases--Huntington's disease [TgN(HD82Gln)81Dbo; referred to as HD mice] and amyotrophic lateral sclerosis [Tg(SOD1G93A)(dl)1/GurJ; referred to as SOD1 mice]--and in a mutant strain with subtle gait abnormalities, C-Snap25(Bdr)/H (Blind-drunk, Bdr). In both models of progressive disease, as with the third mutant, we could reliably and consistently detect specific motor function deficits at ages far earlier than any previously recorded symptoms in vivo: 7-8 weeks for the HD mice and 12 weeks for the SOD1 mice. We also conducted longitudinal analysis of rotarod and grip strength performance, for which deficits were still not detectable at 12 weeks and 23 weeks, respectively. Several new parameters of motor behaviour were uncovered using principal component analysis, indicating that the wheel-running assay could record features of motor function that are independent of rotarod performance. This represents a powerful new method to detect motor deficits at pre-symptomatic stages in mouse disease models and should be considered as a valid tool to investigate the efficacy of therapeutic agents.

Project description:BackgroundSeveral scoring systems are used to assess fecal incontinence (FI), among which, the most commonly used are Wexner and Vaizey's scoring systems. However, there are significant lacunae in these scoring systems, due to which they are neither accurate nor comprehensive.AimTo develop a new scoring system for FI that is accurate, comprehensive, and easy to use.MethodsA pro forma was made in which six types of FI were included: solid, liquid, flatus, mucous, stress, and urge. The weight for each FI was determined by asking a group of patients and laypersons to give a disability score to each type of FI from 0 to 100 (0- least, 100- maximum disability). The disability was assessed on a modified EQ-5D+ (EuroQol) description system, 4D3L (4 dimensions and 3 levels) for each FI. The average score of each FI was calculated, divided by 10, and rounded off to determine the weight of each FI type. The scores for the three levels of frequency of each FI were assigned as never = 0 (No episode of FI ever), occasional = 1 (≤ 1 episode of FI/ wk), and common = 2 (> 1 episode of FI/ wk), and was termed as frequency score. The score for each FI would be derived by multiplying the frequency score and the weight for that FI type. In the second phase of the study, a group of colorectal surgeons was asked to rank the six FI types in order of severity, and their ranking was compared with the patient and laypersons' rankings.ResultsFifty patients and 50 laypersons participated in the study. The weight was assigned to each FI (solid-8, liquid-8, urge-7, flatus-6, mucus-6, and stress-5), and an new scoring system was formulated. The maximum possible score was 80 (total incontinence), and the least 0 (no incontinence). The surgeons' ranking of FI severity did not correlate well with patients' and laypersons' rankings of FI, highlighting that surgeons and patients may perceive the severity of FI differently.ConclusionA new scoring system for FI was formulated, which was simple, logical, comprehensive, and easy to use, and eliminated previous shortcomings. Patients' and surgeons' perceptions of FI severity of FI did not correlate well.

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Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats.

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Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats.

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