Abelson, KSP

Brønnum-Pedersen, T

Heegaard, AM

Hestehave, S

Munro, G

English

UCL Discovery

Scientific presentations at the 2017 Annual Meeting / Scandinavian Journal of Pain 16 (2017) 165–188 187Choice of rat strain in pre-clinical pain-research– Does it make a difference for translation fromanimal model to human condition?S. Hestehave a,b,∗, G. Munro a,c, T.Brønnum-Pedersen d, A.M. Heegaard e, K.S.P.Abelson ba Department of In Vivo Neurodegeneration, H.Lundbeck A/S, Valby, Denmarkb Department of Experimental Medicine, Faculty ofHealth and Medical Sciences, University ofCopenhagen, Denmarkc Department of Neurology, Danish Headache Center,Glostrup Research Institute, Glostrup, Denmarkd Department of Non-Clinical Safety Research, H.Lundbeck A/S, Valby, Denmarke Department Drug Design and Pharmacology,Faculty of Health and Medical Sciences, Copenhagen,DenmarkE-mail address: sara.kristensen@sund.ku.dk (S. Hestehave).Aims: Translating preclinical drug-efficacy of analgesics fromanimal models to humans has proven challenging with manyfailures. Reasons are likely multifaceted, but lack of sufficiently rig-orous study design, and phenotypical relevant animal models maybe part of the explanation. Chronic pain is often associated withsubstantial comorbid burden, consisting of changes in affectivestate and cognitive impairment amongst other behavioral distur-bances. Accordingly, many preclinical pain research activities havestarted to include assessment of comorbidity as a possible experi-mental outcome measure, but surprisingly, little consideration hasbeen paid to the influence of animal-related factors to pain models.To address this essential issue, we have embarked on several com-parative experiments in different pain-models, comparing SpragueDawley’s (SD) from two different vendors with different inbredrat strains (Lewis (LEW), Fisher (F344) and Wistar Kyoto (WKY))selected based on reported stress, depression, inflammatory andpain phenotypes.Methods: Male rats were characterized in acute (hot-plate),inflammatory (Complete Freund’s Adjuvant (CFA)) and neuropathic(Spared Nerve Injury (SNI)) pain models, with dose-response tomorphine (0.3–6.0 mg/kg) in hot-plate, CFA-induced hyperalgesia,and a locomotor motility-assay (LMA).Results: F344 and SD’s were sensitive to morphine in hot-plate and CFA (Minimum Effective Dose (MED) = 3.0 mg/kg). WKYrats developed a less robust mechanical hypersensitivity after CFAinjection, and were less sensitive to morphine in both pain-tests(MED = 6.0 mg/kg). LEW rats were completely insensitive to mor-phine in the hot plate, in contrast to reversal of CFA-inducedhyperalgesia (MED = 3.0 mg/kg). Additionally, neuropathic sensi-tivity developed with a later onset and less robustly in this strainafter SNI. All strains tested in LMA exhibited sedative effects at3.0 mg/kg.Conclusions: Sensory phenotyping in response to acute, inflam-matory and neuropathic pain, and sensitivity to morphine in thesestrains indicates that different pathophysiological mechanisms areengaged after injury. This could have profound implications fortranslating preclinical drug discovery efforts into pain-patients.http://dx.doi.org/10.1016/j.sjpain.2017.04.063View publication stats

Choice of rat strain in pre-clinical pain-research – Does it make a difference for translation from animal model to human condition?

https://discovery.ucl.ac.uk/10083603/7/Kristensten%20Hestehave%20et%20al%20Scand%20J%20Pain%202017_edit.pdf

Choice of rat strain in pre-clinical pain-research – Does it make a difference for translation from animal model to human condition?

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