Pros and Cons of Clinically Relevant Methods to Assess Pain in Rodents

Abstract

The primary objective of preclinical pain research is to improve the treatment of pain. Decades of research using pain-evoked tests has revealed much about mechanisms but failed to deliver new treatments. Evoked pain-tests are often limited because they ignore spontaneous pain and motor or disruptive side effects confound interpretation of results. New tests have been developed to focus more closely on clinical goals such as reducing pathological pain and restoring function. The objective of this review is to describe and discuss several of these tests. We focus on: Grimace Scale, Operant Behavior, Wheel Running, Burrowing, Nesting, Home Cage Monitoring, Gait Analysis and Conditioned Place Preference/ Aversion. A brief description of each method is presented along with an analysis of the advantages and limitations. The pros and cons of each test will help researchers identify the assessment tool most appropriate to meet their particular objective to assess pain in rodents. These tests provide another tool to unravel the mechanisms underlying chronic pain and help overcome the translational gap in drug development.

Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies

“…The tail‐flick and hot‐plate tests are most commonly used to evaluate the analgesic efficacy of drugs, whereas the Hargreaves and von Frey tests are used to evaluate both analgesia and pain‐like states (hyperalgesia/allodynia). However, based on the considerable lack of translational efficacy of putative analgesics as examined via these preclinical methods, many researchers are now transitioning away from reflex‐based assays toward more cognitive and motivational tasks that are thought to be more related to the negative affective components of pain (e.g., Pahng and Edwards, ; Tappe‐Theodor et al, ).…”

Critical evaluation of animal models of visceral pain for therapeutics development: A focus on irritable bowel syndrome

“…One question is whether a spontaneous behavior indicative of pain in rodents exists and is not being measured (a technical limitation) or if there truly is no spontaneous pain (a limitation of the model). Several assays have been developed to attempt to measure spontaneous pain in rodents with neuropathic or inflammatory pain, such as the grimace scale, conditioned place preference/aversion, and monitoring spontaneous home cage activity . While the grimace scale is starting to be applied to studies of visceral pain in colitis models with active inflammation, this type of visceral pain does not model hypersensitivity in IBS patients, and measurements after resolution of the inflammation still require colonic distension to evoke a response.…”

“…Several assays have been developed to attempt to measure spontaneous pain in rodents with neuropathic or inflammatory pain, such as the grimace scale, conditioned place preference/aversion, and monitoring spontaneous home cage activity. 57 While the grimace scale is starting to be applied to studies of visceral pain in colitis models with active inflammation, this type of visceral pain does not model hypersensitivity in IBS patients, and measurements after resolution of the inflammation still require colonic distension to evoke a response. Conditioned place preference/aversion has been used for assessing spontaneous pain in models of neuropathy and to test efficacy of analgesics, but this technique has yet to be applied to studies of visceral hypersensitivity.…”

Decoding spontaneous pain from brain cellular calcium signals using deep learning

“…Although these methods have been successfully applied in several pain models, they have inevitable limitations. The GS cannot predict subchronic or chronic pain 2 , and CPP has limitations related to time resolution and cannot be used alongside drugs that impact reward response or learning and memory 4 . Thus, there is an unmet need for a new methodology to objectively evaluate spontaneous pain.…”