Sex differences in opioid receptor mediated effects: Role of androgens

Sharp, Jessica L.; Pearson, Tallia; Smith, Mark A.

doi:10.1016/j.neubiorev.2022.104522

Cited by 31 publications

(21 citation statements)

References 252 publications

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“…60 Interestingly, only a few studies have explored for differences between men and women in placebo analgesia. 138,186 Women are also more likely to use prescription opioids and have negative psychological effects, 166 whereas men may have a higher overdose risk. 87 However, in systematic review of opioid studies of pain relief, Pisanu et al 143 found less convincing evidence for sex differences, but did report that moderators, such as age, need to be considered.…”

Section: Responses To Pain Treatmentmentioning

confidence: 99%

“…The observation that differences in men and women's pain emerge around puberty led to investigations into the role sex hormones have on pain, 60,121,166 with suggestion that oestrogen and/or progesterone increases the vulnerability to pain, whereas testosterone has protective effects. 46 To test this, explorations into whether pain and analgesia vary across the menstrual cycle have been conducted.…”

Section: Biological Factorsmentioning

confidence: 99%

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Sex and gender differences in pain: past, present, and future

Keogh

2022

Pain

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Section: Responses To Pain Treatmentmentioning

confidence: 99%

Section: Biological Factorsmentioning

confidence: 99%

Sex and gender differences in pain: past, present, and future

Keogh

2022

Pain

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“…Most opioid users report ‘pain’ as their primary reason for opioid misuse 104 . Despite documented sex differences in pain prevalence 24,105 , nociception 106,107 , opioid sensitivity/analgesia 26,28 , and tolerance 108 , - no preclinical research to date has evaluated chronic pain effects opioid use in a sex specific manner. Our results are novel in that they begin to address a major gap in our current understanding of the relationship between pain and opioid misuse.…”

Section: Discussionmentioning

confidence: 99%

Time-dependent enhancement in ventral tegmental area dopamine neuron activity drives pain-facilitated fentanyl intake in males

Higginbotham

Abt

Teich

et al. 2022

Preprint

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Pain affects over 50% of US adults. Opioids are potent analgesics used to treat pain symptoms but are highly prone to abuse, creating a major dilemma for public health. Evidence suggests that the proclivity for opioid abuse under pain conditions varies between sexes. However, the neural mechanisms underlying sex-specific effects of pain on opioid use are largely unclear. Here, we recapitulate clinical findings and demonstrate that pain increases self-administration of the widely abused opioid, fentanyl, selectively in male rats. These behavioral effects develop over time and are paralleled by sex- and pain-specific effects on fentanyl-evoked ventral tegmental area (VTA) dopamine (DA) neuron activity, a critical mediator of motivation and reward. Using in vivo fiber photometry, we show that tonic VTA DA neuron activity is attenuated in males with pain. In contrast, phasic VTA DA neuron responses to self-administered fentanyl increase in magnitude at later timepoints and correspond with increases in fentanyl intake. The protracted increase in fentanyl-evoked VTA DA activity is necessary for pain to enhance fentanyl self-administration in males because chemogenetic inhibition of VTA DA neurons normalized fentanyl intake and associated fentanyl-evoked VTA DA neuron responses. These findings reveal time-dependent and sex-specific pain-induced adaptations to VTA DA neuron function that underlie maladaptive patterns of opioid use.

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“…At the central level, dopaminergic and serotonergic systems appear to play an important role in sexual response, although adrenergic, cholinergic and other neuropeptide systems also contribute (Calabrò et al, 2019). T also participates in the excitatory and inhibitory processes of sexual functions, modulating the activity of neurotransmitter systems, especially dopaminergic (Jordan et al, 2011a; Bell & Sisk, 2013) and opioid peptides (Sharp et al, 2022). Recently, it has been observed that T neurally‐produced increased dopamine signalling in the mesocorticolimbic system (Tomm et al, 2022) and in the extrapyramidal system (Przybylska et al, 2021).…”

Section: Androgensmentioning

confidence: 99%

Androgens, brain and androgen deprivation therapy in paraphilic disorders: A narrative review

2022

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Sexual delinquency is a global problem where those with paraphilic disorders, such as paedophiles, are more likely to commit and reoffend. Androgen deprivation therapy (ADT) has been suggested as a solution. The objective of this narrative review is to present current information on its risks, benefits and limitations as a treatment for paraphilias. The importance of testosterone in sexual function, the effect of its deficiency by age or by pharmacological treatment (anti‐androgens, GnRH agonists and GnRH antagonists) and the effect of testosterone replacement therapy will be reviewed. The relationship between androgens, brain, sexual behaviour and pathophysiology of paraphilic disorders will also be explored. ADT reduces sexual urges, but has adverse effects and, because its reversible nature, it does not ensure less recidivism. Likewise, the research quality of ADT drugs is limited and not enough to support their use. Child sex offenders, and not paraphilic subjects who have not committed assaults, show signs of elevated prenatal exposure to androgens and a higher methylation state of the androgen receptor gene. Sexual behaviour is regulated by subcortical (hypothalamus, brainstem and spinal cord) and cortical structures of the brain, in addition to brain circuits (dopaminergic, serotonergic). Those with paraphilic disorders show abnormalities at these levels that could relate to the risk of sexual offences. In conclusion, androgens represent a significant part of the pathophysiology of paraphilias and therefore, ADT seems promising. Nonetheless, more studies are needed to make definite conclusions about the efficacy of long‐term ADT in paraphilic patients.

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Sex differences in opioid receptor mediated effects: Role of androgens

Cited by 31 publications

References 252 publications

Sex and gender differences in pain: past, present, and future

Sex and gender differences in pain: past, present, and future

Time-dependent enhancement in ventral tegmental area dopamine neuron activity drives pain-facilitated fentanyl intake in males

Androgens, brain and androgen deprivation therapy in paraphilic disorders: A narrative review

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