Deficits in Burrowing Behaviors Are Associated With Mouse Models of Neuropathic but Not Inflammatory Pain or Migraine.

Andrew J Shepherd,Megan E Cloud,Durga P Mohapatra,Yu-Qing Cao

doi:10.3389/fnbeh.2018.00124

Abstract

Burrowing, or the removal of material from an enclosed tube, is emerging as a prominent means of testing changes in a voluntary behavior in rodent models of various pain states. Here, we report no significant differences between male and female mice in terms of burrowing performance, in a substantially shorter time frame than previous reports. We found that the color of the burrow tube affects the variability of burrowing performance when tested in a lit room, suggesting that light aversion is at least a partial driver of this behavior. Spared nerve injury (SNI; as a model of neuropathy) impairs burrowing performance and correlates with enhanced mechanical sensitivity as assessed by von Frey filaments, as well as being pharmacologically reversed by an analgesic, gabapentin. Loss of the SNI-induced burrowing deficit was observed with daily testing post-surgery, but not when the testing interval was increased to 5 days, suggesting a confounding effect of daily repeat testing in this paradigm. Intraplantar complete Freund’s adjuvant (as a model of inflammatory pain) and systemic nitroglycerin (as a model of migraine-like symptoms) administration did not induce any burrowing deficit, indicating that assessment of burrowing behavior may not be universally suitable for the detection of behavioral changes across all rodent pain models.

Highlights

Pre-clinical animal models of painful pathologies have historically relied upon stimulus-evoked assessment of pain sensitivity, such as the Hargreaves test for thermal sensitivity and von Frey filament-based assessment of mechanical sensitivity
Analgesic drug development has been impeded by the types of pre-clinical models of human pain pathologies (Barrot, 2012; Clark, 2016)
The development of novel, voluntary, non-reflexive assays of pain behaviors in rodents aims to improve the translation of pre-clinical findings into clinical developments

Summary

Introduction

Pre-clinical animal models of painful pathologies have historically relied upon stimulus-evoked assessment of pain sensitivity, such as the Hargreaves test for thermal sensitivity and von Frey filament-based assessment of mechanical sensitivity. With the goal of enhancing the translational potential of preclinical findings in pain research, newer assays have been developed that assess changes in voluntary or operant behaviors as surrogate pain measures, those behaviors that are depressed in animals experiencing pain (Langford et al, 2010; Negus et al, 2010; Mogil, 2015; Harte et al, 2016; Sheahan et al, 2017; Shepherd and Mohapatra, 2018) One such example is burrowing, an ancient, adaptive behavior conserved across many rodent species, and one in which various laboratory strains of mice and rats spontaneously engage.

Methods

Results

Conclusion