uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Predictive validity of behavioural animal models for chronic pain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
2011 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 164, no 4, 1195-1206 p.Article, review/survey (Refereed) Published
Abstract [en]

Rodent models of chronic pain may elucidate pathophysiological mechanisms and identify potential drug targets, but whether they predict clinical efficacy of novel compounds is controversial. Several potential analgesics have failed in clinical trials, in spite of strong animal modelling support for efficacy, but there are also examples of successful modelling. Significant differences in how methods are implemented and results are reported means that a literature-based comparison between preclinical data and clinical trials will not reveal whether a particular model is generally predictive. Limited reports on negative outcomes prevents reliable estimate of specificity of any model. Animal models tend to be validated with standard analgesics and may be biased towards tractable pain mechanisms. But preclinical publications rarely contain drug exposure data, and drugs are usually given in high doses and as a single administration, which may lead to drug distribution and exposure deviating significantly from clinical conditions. The greatest challenge for predictive modelling is, however, the heterogeneity of the target patient populations, in terms of both symptoms and pharmacology, probably reflecting differences in pathophysiology. In well-controlled clinical trials, a majority of patients shows less than 50% reduction in pain. A model that responds well to current analgesics should therefore predict efficacy only in a subset of patients within a diagnostic group. It follows that successful translation requires several models for each indication, reflecting critical pathophysiological processes, combined with data linking exposure levels with effect on target.

Place, publisher, year, edition, pages
2011. Vol. 164, no 4, 1195-1206 p.
Keyword [en]
behavioural pharmacology, neuropathic pain, nociceptive pain, inflammatory pain, arthritis, predictive validity, animal models, translation
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-260056DOI: 10.1111/j.1476-5381.2011.01300.xISI: 000295218600008PubMedID: 21371010OAI: oai:DiVA.org:uu-260056DiVA: diva2:846203
Available from: 2015-08-14 Created: 2015-08-14 Last updated: 2015-08-14Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Surgical Sciences
In the same journal
British Journal of Pharmacology
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 149 hits
ReferencesLink to record
Permanent link

Direct link