What can rats tell us about neuropathic pain? Critical evaluation of behavioral tests used in rodent pain models

Background and Purpose: Animal models are a necessity in the study of neuropathic pain, and much of what we know about pain comes from studies in mice and rats. However, very few basic discoveries have been translated so far from rodent models into effective pain therapy. This review presents the most important rat models used in basic pain research, discusses their limitations and recommends better use of these models in future studies. Materials and Methods: A critical review of existing literature on rat models of neuropathic pain is made. Different models are compared and their contribution to pain research presented. Results: There are numerous models of neuropathic pain, and each has its advantages and disadvantages. However, much methodological diversity exists and different interpretations of behavioral tests are used to assess pain in animal models. These methodological differences need to be resolved in order to achieve translation of research results into successful clinical therapeutics. Conclusions: Results of behavioral tests in animal pain models should be considered with caution. Further refinement of animal models of pain and associated methodologies is important. More work is needed for determination of the most predictive animal models, removal of user bias and introduction of more complex outcome measures in behavioral tests. Pain research became a hot topic in the 1970s and 1980s when publication of the gate control theory and the founding of the International Association for the Study of Pain (IASP) attracted many researchers to the field and sparked an explosion in pain research. Much of what we know about pain comes from studies in mice and rats, and the goal of pain research has always been development of practical applications that can lead to pain relief for those who need it. Patients have the right to be pain free. However, their physicians still rely on the »old« drugs, initially developed for indications other than neuropathic pain, a special pain condition that results from damage to or dysfunction of the nervous system. Meta-analyses of randomized clinical trials (RCTs) have identified several drugs that are effective across a range of neuropathic pain disorders (1). The majority are tricyclic antidepressants, opioids, topical sodium channel blockers and anti-epileptic drugs with diverse mechanisms of action. Most of them DAMIR SAPUNAR LIVIA PULJAK Laboratory for Pain Research Department of Anatomy, Histology and Embryology University of Split School of Medicine [oltanska 2, 21000 Split, Croatia Correspondence: Damir Sapunar Laboratory for Pain Research Department of Anatomy, Histology and Embryology, University of Split School of Medicine [oltanska 2, 21000 Split, Croatia Received March 10, 2009. PERIODICUM BIOLOGORUM UDC 57:61 VOL. 111, No 2, 155–160, 2009 CODEN PDBIAD ISSN 0031-5362