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Войти в исследования Neuropharmacology · 2026
Glucocorticoid receptor blockade reverses heroin and alcohol withdrawal-induced hyperalgesia in rats.
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Skandan Neha, Acosta Valeria P, Vendruscolo Janaina C M, McGinn M Adrienne, Vendruscolo Leandro F
Аннотация
RATIONALE: Alcohol use disorder (AUD) and opioid use disorder (OUD) are associated with dysregulation of the hypothalamic-pituitary-adrenal axis and extrahypothalamic stress systems, including glucocorticoid receptor (GR) signaling. Hyperalgesia is defined as an increased sensitivity to nociceptive stimuli and is a prominent symptom of alcohol and opioid withdrawal, which is hypothesized to contribute to the development and persistence of AUD and OUD and heighten relapse vulnerability.
OBJECTIVE: We tested the hypothesis that GR antagonism reverses hyperalgesia during both alcohol and opioid withdrawal.
METHODS: Male and female Wistar rats were either made alcohol-dependent through chronic, intermittent alcohol vapor exposure or made opioid-dependent via daily, subcutaneous heroin injections (1-6 mg/kg). Mechanical and thermal nociceptive sensitivity were assessed 6-8 h into spontaneous withdrawal using the von Frey and Hargreaves tests, respectively.
RESULTS: In male rats, withdrawal from alcohol and heroin produced both mechanical and thermal hyperalgesia. The nonselective GR antagonist mifepristone reduced thermal and mechanical hyperalgesia in alcohol-dependent but not control male rats. Mifepristone reduced thermal but not mechanical sensitivity in heroin-dependent and control male rats. In female rats, alcohol withdrawal produced thermal but not mechanical hyperalgesia. Thermal hyperalgesia was reversed by mifepristone in female alcohol-dependent rats. In contrast, heroin withdrawal produced mechanical hyperalgesia that was insensitive to mifepristone but reversed by the selective GR antagonist miricorilant.
CONCLUSION: These findings reveal sex- and nociception modality-specific differences in alcohol and opioid withdrawal-induced hyperalgesia and highlight GR signaling as a potential therapeutic target for managing drug withdrawal-related pain.
OBJECTIVE: We tested the hypothesis that GR antagonism reverses hyperalgesia during both alcohol and opioid withdrawal.
METHODS: Male and female Wistar rats were either made alcohol-dependent through chronic, intermittent alcohol vapor exposure or made opioid-dependent via daily, subcutaneous heroin injections (1-6 mg/kg). Mechanical and thermal nociceptive sensitivity were assessed 6-8 h into spontaneous withdrawal using the von Frey and Hargreaves tests, respectively.
RESULTS: In male rats, withdrawal from alcohol and heroin produced both mechanical and thermal hyperalgesia. The nonselective GR antagonist mifepristone reduced thermal and mechanical hyperalgesia in alcohol-dependent but not control male rats. Mifepristone reduced thermal but not mechanical sensitivity in heroin-dependent and control male rats. In female rats, alcohol withdrawal produced thermal but not mechanical hyperalgesia. Thermal hyperalgesia was reversed by mifepristone in female alcohol-dependent rats. In contrast, heroin withdrawal produced mechanical hyperalgesia that was insensitive to mifepristone but reversed by the selective GR antagonist miricorilant.
CONCLUSION: These findings reveal sex- and nociception modality-specific differences in alcohol and opioid withdrawal-induced hyperalgesia and highlight GR signaling as a potential therapeutic target for managing drug withdrawal-related pain.