Contextual control of conditioned pain tolerance and endogenous analgesic systems
- Purdue University, United States
- McGill University, Canada
- University of Wisconsin-Milwaukee, United States
- Medical College of Wisconsin, United States
Abstract
The mechanisms underlying the transition from acute to chronic pain are unclear but may involve the persistence or strengthening of pain memories acquired in part through associative learning. Contextual cues, which comprise the environment in which events occur, were recently described as a critical regulator of pain memory; both male rodents and humans exhibit increased pain sensitivity in environments recently associated with a single painful experience. It is unknown, however, how repeated exposure to an acute painful unconditioned stimulus in a distinct context modifies pain sensitivity or the expectation of pain in that environment. To answer this question, we conditioned mice to associate distinct contexts with either repeated administration of a mild visceral pain stimulus (intraperitoneal injection of acetic acid) or vehicle injection over the course of three days. On the final day of experiments animals received either an acid injection or vehicle injection prior to being placed into both contexts. In this way, contextual control of pain sensitivity and pain expectation could be tested respectively. When re-exposed to the noxious stimulus in a familiar environment, both male and female mice exhibited context-dependent conditioned analgesia, a phenomenon mediated by endogenous opioid signaling. However, when expecting the presentation of a painful stimulus in a given context, males exhibited conditioned hypersensitivity whereas females exhibited endogenous opioid-mediated conditioned analgesia. These results are evidence that pain perception and engagement of endogenous opioid systems can be modified through their psychological association with environmental cues. Successful determination of the brain circuits involved in this sexually dimorphic anticipatory response may allow for the manipulation of pain memories, which may contribute to the development of chronic pain states.
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All data generated or analyzed during this study are included in the manuscript,
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Funding
National Institutes of Health (K99HL155791)
- Katelyn E Sadler
National Institutes of Health (R01NS070711)
- Cheryl L Stucky
National Institutes of Health (R37NS108278)
- Cheryl L Stucky
Advancing a Healthier Wisconsin
- Cheryl L Stucky
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All protocols were in accordance with National Institute of Health guidelines and were approved by the Institutional Animal Care and Use Committee at the Medical College of Wisconsin (Milwaukee, WI; protocol #0383).
Copyright
© 2022, Trask et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Contextual control of conditioned pain tolerance and endogenous analgesic systems
eLife 11:e75283.
https://doi.org/10.7554/eLife.75283
