Pharmacological mechanisms of alcohol analgesic-like properties in mouse models of acute and chronic pain

Bradley Neddenriep, Deniz Bagdas, Katherine M. Contreras, Joseph W. Ditre, Jennifer T. Wolstenholme, Michael F. Miles, M. Imad Damaj

Research output: Contribution to journalArticle

Abstract

Alcohol use and chronic pain are highly comorbid. Acute alcohol use typically produces an analgesic effect. However, chronic use can worsen the progression of chronic pain. In rodent models, acute models of pain have primarily been used to investigate the relationship between alcohol and pain analgesia. Here, we use two models of chronic pain, chronic inflammatory and peripheral neuropathic pain, to investigate acute alcohol's antinociceptive and analgesic properties. We hypothesize that acute ethanol is acting through opioid receptors to create an analgesic-like effect in both reflexive and affective dimensions of pain. Using male and female C57BL/6J mice, oral ethanol administration (0–1.25 g/kg) showed a dose-dependent reversal of mechanical hypersensitivity in both Complete Freund's Adjuvant (CFA) and chronic constriction injury (CCI) models of chronic inflammatory and neuropathic pain. No sex differences were observed. Using the conditioned place preference (CPP) task to assess the subjective responses to ethanol's anti-nociceptive properties, CCI-injured animals showed a preference for the ethanol-paired side, suggesting a reduction in an aversive and pain-like state produced by nerve injury. These effects are likely mediated through the kappa and possibly the mu opioid systems, since ethanol-induced anti-nociception following CCI was fully reversed by pretreatment with the kappa selective antagonist, nor-BNI, or high doses of naltrexone. These data show that ethanol possesses analgesic-like properties in chronic inflammatory and neuropathic pain models in mice and provide new insight into ethanol as it relates to chronic pain.

Original languageEnglish (US)
Article number107793
JournalNeuropharmacology
Volume160
DOIs
StatePublished - Dec 1 2019

Fingerprint

Acute Pain
Chronic Pain
Analgesics
Ethanol
Alcohols
Pharmacology
Neuralgia
Constriction
Wounds and Injuries
Pain
Naltrexone
Nociception
Freund's Adjuvant
Opioid Receptors
Inbred C57BL Mouse
Sex Characteristics
Analgesia
Opioid Analgesics
Oral Administration
Rodentia

Keywords

  • Alcohol pain mice chronic

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Neddenriep, B., Bagdas, D., Contreras, K. M., Ditre, J. W., Wolstenholme, J. T., Miles, M. F., & Damaj, M. I. (2019). Pharmacological mechanisms of alcohol analgesic-like properties in mouse models of acute and chronic pain. Neuropharmacology, 160, [107793]. https://doi.org/10.1016/j.neuropharm.2019.107793

Pharmacological mechanisms of alcohol analgesic-like properties in mouse models of acute and chronic pain. / Neddenriep, Bradley; Bagdas, Deniz; Contreras, Katherine M.; Ditre, Joseph W.; Wolstenholme, Jennifer T.; Miles, Michael F.; Damaj, M. Imad.

In: Neuropharmacology, Vol. 160, 107793, 01.12.2019.

Research output: Contribution to journalArticle

Neddenriep, Bradley ; Bagdas, Deniz ; Contreras, Katherine M. ; Ditre, Joseph W. ; Wolstenholme, Jennifer T. ; Miles, Michael F. ; Damaj, M. Imad. / Pharmacological mechanisms of alcohol analgesic-like properties in mouse models of acute and chronic pain. In: Neuropharmacology. 2019 ; Vol. 160.
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