Differential modulation of thermal preference after sensitization by optogenetic or pharmacological activation of heat-sensitive nociceptors

Abstract

Common approaches to studying chronic pain in pre-clinical animal models paradoxically involve measuring reflexive withdrawal responses that are more indicative of acute nociceptive pain. These methods typically do not capture the ongoing nature of chronic pain nor report on behavioral changes associated with pain. In addition, data collection and analysis protocols are often labour-intensive and require direct investigator interactions, potentially introducing bias. In this study, we develop and characterize a low-cost, easily assembled behavioral assay that yields self-reported temperature preference from mice which is sensitive to peripheral sensitization protocols. This system uses a partially automated and freely available analysis pipeline to streamline the data collection process and enable objective analysis. We found that after intraplantar administration of the TrpV1 agonist, capsaicin, mice preferred to stay in cooler temperatures than control injected mice. We further observed that gabapentin, a non-opioid analgesic commonly prescribed to treat chronic pain, reversed this aversion to higher temperatures. We further observed that optogenetic activation of the central terminals of TrpV1+ primary afferents via in vivo spinal light delivery did not induce a similar change in thermal preference, indicating a role for peripheral nociceptor activity in the modulation of temperature preference. We conclude that this easily produced and robust sensory assay provides an alternative approach to investigate the contribution of central and peripheral mechanisms to pathological sensory processing that does not rely on reflexive responses evoked by noxious stimuli.