An animal model simulates components of human disease in animals. The animal models of pain used currently in the pharmaceutical industry have a poor track record of predicting clinical efficacy with investigational new analgesics. So, industry needs better animal models in order to validate novel mechanisms for the treatment of pain and to confidently discover new analgesic agents that are expected to work well in patients.
The work package aims to deliver three new rat models of neuropathic disorders where the pathophysiological changes that cause the pain are more relevant to human disease. These are diabetic neuropathy, neuropathy induced by antiretroviral treatment and chemotherapy-induced neuropathy. We also studying a key mediator of human pain, nerve growth factor (NGF) and profiling hypersensitivity in the rqt.
At present, measurements of pain-related behaviour in animal models are based on the reaction to different transient noxious stimuli, e.g. mechanical hypersensitivity. New outcome measures are being exploring in two areas. Firstly we are measuring pain related behaviours which do not require a painful stimulus and therefore inform us about spontaneous or ongoing pain. Ongoing pain is the symptom that pain patients complain about most. The work package has developed a number of ways of measuring ongoing pain in rats – fentanyl self-administration, conditioned place preference and spontaneous activity in afferent C-fibres measured by microneurography. Using these methods, the next step is to determine whether ongoing pain-like behaviour can be identified in currently-used models. Secondly, we are measuring rodent behaviours indicating anxiety-like behaviour and deficits in cognitive function and general well-being which can be caused by chronic pain and are relevant to the adverse changes experienced by pain patients. In particular, a new measure of general well-being in rats, burrowing performance, appears to be reliably attenuated by pain in the models used.
Timeline and participants in Europain workpackage 2 on improving animal models of pain.
Another measure of clinical relevance which has emerged recently is the increased hypersensitivity to pain stimuli caused by sleep restriction in rats. This correlates well with the findings in work package 3 of increased pain sensitivity in sleep-deprived human volunteers.
A number of consensus meetings will be held to recommend guidelines on critical preclinical issues in pain research, such as eliminating experimental bias and better translation of animal models to humans. Methods for both established and new models and measures used in the workpackage will be written up and archived in the Europain protocol library.