Sex Differences in μ-Opioid Receptor Expression in the Rat Midbrain Periaqueductal Gray Are Essential for Eliciting Sex Differences in Morphine Analgesia
| Autor: | Anne Z. Murphy, Dayna R. Loyd, Xioaya Wang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Microinjections medicine.drug_class Freund's Adjuvant Population Receptors Opioid mu Gene Expression Estrous Cycle Pharmacology Periaqueductal gray Article Rats Sprague-Dawley Opioid receptor Internal medicine Reaction Time medicine Animals Periaqueductal Gray Opioid peptide education Pain Measurement Neurons Sex Characteristics education.field_of_study Dose-Response Relationship Drug Morphine General Neuroscience Saporins Rats Endocrinology Opioid Peptides nervous system Opioid Hyperalgesia Ribosome Inactivating Proteins Type 1 Female Rostral ventromedial medulla Opiate Psychology medicine.drug |
| Zdroj: | The Journal of Neuroscience. 28:14007-14017 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.4123-08.2008 |
| Popis: | Opioid-based narcotics are the most widely prescribed therapeutic agent for the alleviation of persistent pain; however, it is becoming increasingly clear that morphine is significantly less potent in women compared with men. Morphine primarily binds to μ-opioid receptors (MORs), and the periaqueductal gray (PAG) contains a dense population of MOR-expressing neurons. Via its descending projections to the rostral ventromedial medulla and the dorsal horn of the spinal cord, the PAG is considered an essential neural substrate for opioid-based analgesia. We hypothesized that MOR expression in the PAG was sexually dimorphic, and that these sex differences contribute to the observed sex differences in morphine potency. Using immunohistochemistry, we report that males had a significantly higher expression of MOR in the ventrolateral PAG compared with cycling females, whereas the lowest level of expression was observed in proestrus females. CFA-induced inflammatory pain produced thermal hyperalgesia in both males and females that was significantly reversed in males with a microinjection of morphine into the ventrolateral PAG; this effect was significantly greater than that observed in proestrus and estrus females. Selective lesions of MOR-expressing neurons in the ventrolateral PAG resulted in a significant reduction in the effects of systemic morphine in males only, and this reduction was positively correlated with the level of MOR expression in the ventrolateral PAG. Together, these results provide a mechanism for sex differences in morphine potency. |
| Databáze: | OpenAIRE |
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