Hypolocomotion, Asymmetrically Directed Behaviors (Licking, Lifting, Flinching, and Shaking) and Dynamic Weight Bearing (Gait) Changes are Not Measures of Neuropathic Pain in Mice

Abstract

BackgroundSpontaneous (non-evoked) pain is a major clinical symptom of neuropathic syndromes, one that is understudied in basic pain research for practical reasons and because of a lack of consensus over precisely which behaviors reflect spontaneous pain in laboratory animals. It is commonly asserted that rodents experiencing pain in a hind limb exhibit hypolocomotion and decreased rearing, engage in both reflexive and organized limb directed behaviors, and avoid supporting their body weight on the affected side. Furthermore, it is assumed that the extent of these positive or negative behaviors can be used as a dependent measure of spontaneous chronic pain severity in such animals. In the present study, we tested these assumptions via blinded, systematic observation of digital video of mice with nerve injuries (chronic constriction or spared nerve injury), and automated assessment of locomotor behavior using photocell detection and dynamic weight bearing (i.e., gait) using the CatWalk® system.ResultsWe found no deficits in locomotor activity or rearing associated with neuropathic injury. The frequency of asymmetric (ipsilaterally directed) behaviors were too rare to be seriously considered as representing spontaneous pain, and in any case did not statistically exceed what was blindly observed on the contralateral hind paw and in control (sham operated and unoperated) mice. Changes in dynamic weight bearing, on the other hand, were robust and ipsilateral after spared nerve injury (but not chronic constriction injury). However, we observed timing, pharmacological, and genetic dissociation of mechanical allodynia and gait alterations.ConclusionsWe conclude that spontaneous neuropathic pain in mice cannot be assessed using any of these measures, and thus caution is warranted in making such assertions.

Stronger Antinociceptive Efficacy of Opioids at the Injured Nerve Trunk Than at Its Peripheral Terminals in Neuropathic Pain

“…Although neuropathy-induced paw lifting was rare in some studies (Mogil et al, 2010;Allchorne et al, 2012), it was relatively frequent in other (Bennett and Xie, 1988;Kim et al, 1997;Djouhri et al, 2006), similar to our observations. A variable degree of nerve injury might account for these differences.…”

Increased Na+ and K+ currents in small mouse dorsal root ganglion neurons after ganglion compression

“…The mice exhibited no obvious "spontaneous" behavior directed at the limb ipsilateral (or contralateral) to the CCD, in accordance with the lack of such behavior in certain other models of neuropathic pain in the mouse (Mogil et al 2010) but contrary to results previously obtained in the rat after CCD .…”

Grid-climbing Behaviour as a Pain Measure for Cancer-induced Bone Pain and Neuropathic Pain

“…The motor function abnormalities linked to introduction of the model have previously prevented assessment of neuropathic pain using gait analysis. In neuropathic models, traditional analgesic compounds, such as morphine and gabapentin, have failed to improve the behavioural readout using standard tool for gait analysis (22,23), thereby suggesting that the observed behaviour was not pain-related but rather caused by motor function abnormalities. However, in this study, a significant decrease in sparing time was induced by administration of morphine, suggesting that the grid-climbing test does in fact quantify pain and not only motor function abnormalities.…”