Analysis of Acute and Chronic Inflammatory Pain‐Depressed Wheel Running in the Rat

Abstract

Traditional pain‐evoked tests (e.g., hot plate and tail withdrawal tests) do not mimic the disruptive effects of pain on daily life, a primary outcome measure used for pain in humans. This mismatch may contribute to the lack of translation of analgesics from the laboratory to the clinic. To solve this problem, we have previously demonstrated that pain‐depressed home cage wheel running is an objective and clinically relevant measure of the functional consequences of chronic inflammatory pain in the rat (Kandasamy et al., 2016, J. Neurosci. Methods). In this study, we extend this approach by assessing the extent to which acute formalin‐induced inflammatory pain depresses wheel running in the rat. The formalin test is a widely used test of acute nociception where animals are monitored for pain‐like behaviors (i.e., guarding or licking the paw) approximately one hour following formalin injection into the hindpaw. Few studies have examined the functional consequences of acute pain; thus, the aim of this study was to examine the effects of formalin‐induced inflammatory pain on function as measured by home cage wheel running. Rats were housed in individual cages containing a computerized running wheel where they remained for the rest of the experiment. Rats were allowed free access to the wheel 23 hours/day for 7 days prior to the induction of hindpaw inflammation to acquire stable running levels. Wheel running during the 23 hours immediately prior to induction of inflammation was used as the baseline. Inflammation was induced with an intraplantar injection of Complete Freund’s Adjuvant (CFA; 0.1 mL) or formalin (5%, 0.05 mL) into the right hindpaw. As expected, CFA almost completely inhibited wheel running in rats in the 23 hours following administration. Mechanical withdrawal thresholds, as measured by the von Frey test, remained low across the entire testing period. In contrast, the functional effects of a single formalin injection were apparent as indicated by decreased wheel running after the first hour following injection. Wheel running was depressed in the absence of mechanical allodynia, suggesting that inflammatory pain‐induced mechanical allodynia and decreased function are independent of each other. Importantly, these results indicate that continuous monitoring of the functional consequences of pain using home cage wheel running reveal insights into changes in behavior resulting from both acute and chronic pain.Support or Funding InformationSupport for this project was provided by a 2019–20 Faculty Support Grant from the California State University Division of Academic Affairs (RK) and funds from the College of Science at California State University, East Bay (RK).