Morphine antinociception on thermal sensitivity and place conditioning in male and female rats treated with intraplantar complete freund’s adjuvant

Armendariz, Alexander; Nazarian, Arbi

doi:10.1016/j.bbr.2018.01.031

Cited by 11 publications

(2 citation statements)

References 42 publications

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“…The effects of morphine on conditioned place preference and conditioned place aversion during peripheral inflammation also are not significantly different between males and females. 8,92 Despite similar levels of pain-like behaviors in both sexes, it is important to note that the mechanisms underlying these behaviors sometimes differ in males vs females. 26,50,89,130,149,178,195 Thus, caution should be exercised when drawing conclusions about positive or negative effects of treatments for pain when males and females are not stratified.…”

Section: Influence Of Sex On Evoked and Spontaneous Nocifensive Behav...mentioning

confidence: 99%

Sex differences in neuroimmune and glial mechanisms of pain

Gregus

Levine

Eddinger³

et al. 2021

Pain

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Pain is the primary motivation for seeking medical care. Although pain may subside as inflammation resolves or an injury heals, it is increasingly evident that persistency of the pain state can occur with significant regularity. Chronic pain requires aggressive management to minimize its physiological consequences and diminish its impact on quality of life. Although opioids commonly are prescribed for intractable pain, concerns regarding reduced efficacy, as well as risks of tolerance and dependence, misuse, diversion, and overdose mortality rates limit their utility. Advances in development of nonopioid interventions hinge on our appreciation of underlying mechanisms of pain hypersensitivity. For instance, the contributory role of immunity and the associated presence of autoimmune syndromes has become of particular interest. Males and females exhibit fundamental differences in innate and adaptive immune responses, some of which are present throughout life, whereas others manifest with reproductive maturation. In general, the incidence of chronic pain conditions, particularly those with likely autoimmune covariates, is significantly higher in women. Accordingly, evidence is now accruing in support of neuroimmune interactions driving sex differences in the development and maintenance of pain hypersensitivity and chronicity. This review highlights known sexual dimorphisms of neuroimmune signaling in pain states modeled in rodents, which may yield potential high-value sex-specific targets to inform future analgesic drug discovery efforts.

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Section: Influence Of Sex On Evoked and Spontaneous Nocifensive Behav...mentioning

confidence: 99%

Sex differences in neuroimmune and glial mechanisms of pain

Gregus

Levine

Eddinger³

et al. 2021

Pain

View full text Add to dashboard Cite

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“…Another advantage of our study is that we verified potentiation of antinociception for more than one compound and opioid combination, in acute noxious heat pain, inflammatory, and post-operative pain models. Notably, we were able to observe significant antinociceptive effects at very low opioid doses in the presence of Comp5 or MS1, compared to the doses used to suppress thermal hyperalgesia in models of peripheral inflammation (Armendariz and Nazarian, 2018;Gaspari et al, 2018). Similarly, using the plantar incision assay, a model of post-operative pain whose induced thermal hypersensitivity can be treated with 3 mg/kg of morphine (Cowie and Stucky, 2019), we could observe antinociception with the PAMs at reduced doses of opioids (2 mg/kg) which by themselves would produce negligible antinociception.…”

Section: Discussionmentioning

confidence: 80%

A Promising Chemical Series of Positive Allosteric Modulators of the μ-Opioid Receptor that Enhance the Antinociceptive Efficacy of Opioids but not their Adverse Effects

Pryce

Kang

Sakloth

et al. 2021

Preprint

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Positive allosteric modulators (PAMs) of the μ-opioid receptor (MOR) have been proposed to exhibit therapeutic potential by maximizing the analgesic properties of clinically used opioid drugs while limiting their adverse effects or risk of overdose as a result of using lower drug doses. We herein report in vitro and in vivo characterization of two small molecules from a chemical series of MOR PAMs that exhibit: (i) MOR PAM activity and receptor subtype selectivity in vitro, (ii) a differential potentiation of the antinociceptive effect of oxycodone, morphine, and methadone in mouse models of pain that roughly correlates with in vitro activity, and (iii) a lack of potentiation of adverse effects associated with opioid administration, such as somatic withdrawal, respiratory depression, and analgesic tolerance. This series of MOR PAMs holds promise for the development of adjuncts to opioid therapy to mitigate against overdose and opioid use disorders.

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