Abstract
Common approaches to studying mechanisms of chronic pain and sensory changes in pre-clinical animal models involve measurement of acute, reflexive withdrawal responses evoked by noxious stimuli. These methods typically do not capture more subtle changes in sensory processing nor report on the consequent behavioral changes. 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 that is responsive to peripheral sensitization. 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 saline injected mice. We further observed that gabapentin, a non-opioid analgesic commonly prescribed to treat chronic pain, reversed this aversion to higher temperatures. In contrast, 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 possible 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 of sensory processing that does not rely on reflexive responses evoked by noxious stimuli.
Highlights
Chronic pain is pain that persists for more than three months without clear protective benefits and can be a disease by itself or arise from another underlying health condition
We found that mice injected with saline showed a preference for a temperature of 32.7 Æ 0.3C (Figure 2(c)), whereas those treated with capsaicin preferred a slightly cooler temperature of 31.3 Æ 0.3C (Figure 2(d))
Comparing both groups via Gaussian fit of each treatment group’s summed positional data over the experiment revealed a small but significant difference between preferred temperatures across the two treatment groups, with capsaicin-treated mice preferring cooler temperatures (Figure 2(e); F(3, 264) 1⁄4 8.53, p < 0.0001). This shift to cooler temperatures was seen within mice with paired analysis of mean preferred temperature after each treatment, indicating that mice consistently showed a preference for cooler temperatures after capsaicin was administered (Figure 2(f); Paired t-test, t5 1⁄4 3.52, p 1⁄4 0.017)
Summary
Chronic pain is pain that persists for more than three months without clear protective benefits and can be a disease by itself or arise from another underlying health condition These conditions may be precipitated by a series of events or a combination of various risk factors that affect multiple dimensions of an individual’s daily life, including their emotional wellbeing, ability to perform daily tasks, and functioning in the workplace.[1,2,3] On a cellular level, pathological pain can arise from neurochemical and circuit level reorganization of primary afferents and spinal dorsal horn neurons.[4,5] These changes manifest in the form of hyperalgesia, where a painful stimulus is perceived as more painful, and allodynia where innocuous stimuli can begin to evoke pain. Thermal and mechanical allodynia are features of many clinical pain conditions.[6,7,8] These are highly debilitating as they make innocuous stimuli
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