Sex Differences in Opioid Analgesia and Addiction: Interactions among Opioid Receptors and Estrogen Receptors

Lee, Cynthia Wei-Sheng; Ho, Ing-Kang

doi:10.1186/1744-8069-9-45

Cited by 97 publications

(98 citation statements)

References 173 publications

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“…For other drugs of abuse, more men use and are addicted to opiates (Lee and Ho, 2013) as well as other drugs (Substance Abuse and Mental Health Services Administration, 2007). However, clinical reports suggest that for all substances, women who become addicted progress through the landmark stages from initial use to dependence at a faster rate than men (Kosten et al, 1993;Brady and Randall, 1999).…”

Section: Sex Differences In Drug Abusementioning

confidence: 99%

Sex Differences in Animal Models: Focus on Addiction

2016

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Section: Sex Differences In Drug Abusementioning

confidence: 99%

Sex Differences in Animal Models: Focus on Addiction

2016

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“…However, sex differences of side effects and efficacy in opioid antinociception, such as analgesia, tolerance, physical dependence and addiction, have been observed and reported in a variety of mammals in the past three decades [3][4][5][6][7]. With the concept of subtypes of receptors and alternative splicing been proposed by previous studies [8][9][10], especially successful isolation and determination of μ opioid receptors variants from a single μ opioid receptor gene [11][12][13][14][15], we realized that these findings might explain the sex differences partially.…”

Section: Introductionmentioning

confidence: 99%

Sex Associated Differential Expressions of the Alternatively Spliced Variants mRNA of OPRM1 in Brain Regions of C57BL/6 Mouse

Liu

Zhang

Qin

et al. 2018

Cell Physiol Biochem

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Background/Aims: Opiates are potent analgesics but their clinical use is limited by sex-associated side effects, such as drug tolerance, opioid-induced hyperalgesia and withdrawal reaction. OPRM1, as the main receptor of opioids, plays an important role in the pharmacological process of opioids in rodents and human. We have previously investigated OPRM1, the μ opioid receptor gene, which have dozens of alternatively spliced variants probably correlating with opioid-induced effects in brain regions of four inbred mouse strains and demonstrated the strain-specific expressions of these splice variants. Also, within a strain, the regional expression patterns of some of the variants were similar while others were opposite. Thus, we are aiming to seek out the relationship between sex differences and these alternatively spliced variants. Methods: The present studies follow a SYBR green quantitative PCR (qPCR) which we had used before to examine the expression of OPRM1 splice variant mRNAs in selected brain regions of male and female C57BL/6 mice. Sex-associated differences in baseline latency, opioid-induced tolerance, analgesia and addiction were examined and determined by Tail-flick test, jumps and statistical analysis. Results: The mRNA levels of opioid receptor gene splice variants in male and female mice showed significant differences among the brain regions, implying region-specific alternative splicing of the OPRM1 gene, which was consistent with our previous study. More importantly, the complete mRNA expression profiles of the OPRM1 splice variants was also gender-specific, suggesting a sexual influence on OPRM1 alternative splicing. Conclusion: In brief, we put forward that the distinctions among baseline latency, opioid-induced tolerance, analgesia and physical dependence in male and female mice might correlate with sex associated differential expressions of OPRM1 gene.

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“…44 There is little evidence of an estrogenic influence in pain processing caused by crosstalk between the estrogen and opioid receptors through classic secondary messengers and downstream gene transcriptional regulators. 45 Several studies support a role for testosterone in dampening pain and raising the pain threshold. 46,47 Additional research is needed to clarify the effects of estrogen and of testosterone on pain modulation and elucidate the potential biological mechanism for such effects.…”

Section: The Gonadal Hormonesmentioning

confidence: 99%

Hormones in pain modulation and their clinical implications for pain control: a critical review

Chen¹,

Zhang²,

Wang³

2016

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Recently, more and more studies have found that pain generation, transmission and modulation are under hormonal regulation. Indeed, hormonal dysregulation is a common component of chronic pain syndromes. Studies have attempted to determine whether the relationship between the pain and its perception and hormones is a causative relationship and how these processes interrelate. This review summarizes and analyzes the current experimental data and provides an overview of the studies addressing these questions. The relationship between pain perception and endocrine effects suggests that hormones can be used as important biomarkers of chronic pain syndromes and/or be developed into therapeutic agents in the fight against pain.

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Sex Differences in Opioid Analgesia and Addiction: Interactions among Opioid Receptors and Estrogen Receptors

Cited by 97 publications

References 173 publications

Sex Differences in Animal Models: Focus on Addiction

Sex Differences in Animal Models: Focus on Addiction

Sex Associated Differential Expressions of the Alternatively Spliced Variants mRNA of OPRM1 in Brain Regions of C57BL/6 Mouse

Hormones in pain modulation and their clinical implications for pain control: a critical review

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