The Operant Plantar Thermal Assay: A Novel Device for Assessing Thermal Pain Tolerance in Mice.

An unexpected finding in this study was that CCI increased rather than decreased time in the reward zone across all temperatures (Fig. 5B and 5C). The representative heat map from this study also shows that CCI animals spent considerable time in regions of a 40°C compartment away from the reward zone and actually appeared to prefer 40°C>30°C...opposite of what was found in non-operated mice (Fig. 2) or sham CCI controls (heat map from Fig. 5B). An implication to consider here is that CCI increased preference for the 40°C plate, perhaps serving as a negative reinforcer to alleviate spontaneous pain in a manner analogous to use of a heating pad in human patients with neuropathic pain.     

Editor's note: this comment is co-authored by Ashlie Reker and Steve Davidson, University of Cincinnati, US.

We were also surprised by the finding that nerve-injured animals spent more time in the reward zone, even when the floor was heated to temperatures that naïve animals found aversive. Dr. Negus raises an interesting hypothesis regarding the mechanism underlying this observation, that the nerve-injured mice are, in a sense, self-medicating with heat. We cannot exclude this as a contributing factor. The individual heat maps show that much of the time on the heated side (although not all, as is correctly pointed out) was directed at the reward zone, suggesting the reward itself contributes to the motivation to remain on the heated side. Nearly all studies, including ours, show that CCI produces thermal hypersensitivity, as measured by reflexive tests. The OPTA indicates that nerve-injured mice overcome this hypersensitivity by choice. The question remains as to whether the capacity to overcome (or tolerate) the thermal stimulation by nerve-injured mice is due to altered afferent processing, such as by occlusion, gate-control, or a state-dependent mechanism such as how scratch inhibits itch, or whether this effect is driven by altered descending modulation, or both. We thank Dr. Negus for his careful assessment of the OPTA and welcome any new insights from its adoption.