Social environment alters opioid‐induced hyperalgesia and antinociceptive tolerance in adolescent mice

Bates, M.L. Shawn; Emery, Michael A.; Wellman, Paul J.; Eitan, Shoshana

doi:10.1002/ejp.825

Cited by 16 publications

(2 citation statements)

References 56 publications

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“…Previous studies demonstrated hyperalgesia to heat stimuli following opioid exposure using the tail flick 18–20,66 , hot plate 21,22,71–73 or Hargreaves tests 18,23,69 . Consistent with prior reports 73 , fentanyl exposed mice developed thermal hyperalgesia at both 20-22 hours spontaneous withdrawal and during precipitated withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Divergent profiles of fentanyl withdrawal and associated pain in mice and rats

Uddin

Jenne

Fox

et al. 2020

Preprint

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Opioid abuse has devastating effects on patients, their families, and society. Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse. The sharp increase in abuse and overdoses arising from the illicit use of potent and rapidly-acting synthetic opioids, such as fentanyl, highlights the urgency of understanding the withdrawal mechanisms related to these drugs. Progress is impeded by inconsistent reports on opioid withdrawal in different preclinical models. Here, using rats and mice of both sexes, we quantified withdrawal behaviors during spontaneous and naloxone-precipitated withdrawal, following two weeks of intermittent fentanyl exposure. We found that both mice and rats lost weight during exposure and showed increased signs of distress during spontaneous and naloxone precipitated withdrawal. However, these species differed in their expression of withdrawal associated pain, a key contributor to relapse in humans. Spontaneous or ongoing pain was preferentially expressed in rats in both withdrawal conditions, while no change was observed in mice. In contrast, withdrawal associated thermal hyperalgesia was found only in mice. These data suggest that rats and mice diverge in how they experience withdrawal and which aspects of the human condition they most accurately model. These differences highlight each species’ strengths as model systems and can inform experimental design in studies of opioid withdrawal.

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Section: Discussionmentioning

confidence: 99%

Divergent profiles of fentanyl withdrawal and associated pain in mice and rats

Uddin

Jenne

Fox

et al. 2020

Preprint

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“…There are numerous tasks of thermal nociception with which to study animal models exhibiting a pain phenotype, with the hot plate test being among the most frequently used. The hot plate test is typically used to dissect the basic mechanisms of thermal nociception, to model hyperalgesia or allodynia observed in painful conditions, or to assess the efficacy of analgesics [3][4][5][6][7]. The cold plate test is used to model cold-based nociception, although its use is less frequent than the hot plate test, and the resulting behavior is often less pronounced [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in choice-based thermal nociceptive tasks in adult rats

Bourgeois

Kopec

2021

Preprint

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Interest in the role of sex as a biological variable continues to increase, including a mandate for the study of both sexes in NIH-funded research. Choice-based thermal nociceptive tests allow for the study of a more spontaneous response to thermal stimuli and avoidance behavior compared to traditional nociceptive assays, and their usage has been increasing in recent years. However, to date no comparison of naïve male and female responses to such tests has been published. As sex differences are known to exist in both human chronic pain conditions and rodent models of nociception, it is critical to understand the impact of sex on any nociceptive assay. Herein, we examined the effect of sex on two choice-based thermal nociceptive tests, the thermal gradient test and the temperature place preference test, in adult rats. We report that marked sex differences exist in responses to these tests. Namely, the activation of a 10° C-to-47° C thermal gradient results in an increase in time spent in the 10° C zone in females, compared to a reduction in males. In a temperature place preference test pairing a surface temperature of 22° C with either 5° C, 10° C, 47° C, or 50° C, males spent less than 50% of their time in every non-22° C zone, but in females this was only observed when testing 50° C. Together, these results suggest that male rats show more avoidance behavior to non-ambient temperatures when given free access to multiple zones, including at temperatures which are milder than those typically used to evoke a nociceptive response in traditional hot and cold plate tests.

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