'Reinventing the wheel' to advance the development of pain therapeutics

Abstract

Chronic pain affects approximately one-third of the population worldwide. The primary goal of animal research is to understand the neural mechanisms underlying pain so better treatments can be developed. Despite an enormous investment in time and money, almost no novel treatments for pain have been developed. There are many factors that contribute to this lack of translation in drug development. The mismatch between the goals of drug development in animals (inhibition of pain-evoked responses) and treatment in humans (restoration of function) is a major problem. To solve this problem, a number of pain-depressed behavioral tests have been developed to assess changes in normal behavior in laboratory animals. The use of home cage wheel running as a pain assessment tool is especially useful in that it is easy to use, provides an objective measurement of the magnitude and duration of pain, and is a clinically relevant method to screen novel drugs. Pain depresses activity in humans and animals, and effective analgesic treatments restore activity. Unlike traditional pain-evoked tests (e.g., hot plate, tail flick, von Frey test), restoration of home cage wheel running evaluates treatments for both antinociceptive efficacy and the absence of disruptive side effects (e.g., sedation, paralysis, nausea). This article reviews the literature using wheel running to assess pain and makes the case for home cage wheel running as an effective and clinically relevant method to screen novel analgesics for therapeutic potential.