Sex-specific differences in alcohol-induced pain sensitization

• Published in: Neuropharmacology Vol. 225; p. 109354
• Main Authors: Alexander, Shevon N., Jeong, Han S., Szabo-Pardi, Thomas A., Burton, Michael D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-03-2023
• Subjects: Alcohol; Alcoholism - complications; Animals; Ethanol - adverse effects; Female; Ganglia, Spinal - pathology; Hyperalgesia - chemically induced; Macrophages - drug effects; Macrophages - pathology; Male; Mice; Microglia; Microglia - drug effects; Microglia - pathology; Neuralgia - chemically induced; Neuralgia - pathology; Neuroglia - drug effects; Neuroglia - pathology; Neuroimmune; Pain; Sensitization; Sex Characteristics; Sex differences; Alcohol; Sex differences; Sensitization; Pain; Neuroimmune; Microglia
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2022.109354

Pain sensitization is a phenomenon that occurs to protect tissues from damage and recent studies have shown how a variety of non-noxious stimuli included in our everyday lives can lead to pain sensitization. Consumption of large amounts of alcohol over a long period of time invokes alcohol use disorder (AUD), a complex pathological state that has many manifestations, including alcohol peripheral neuropathy (neuropathic pain). We asked if ‘non-pathological’ alcohol consumption can cause pain sensitization in the absence of other pathology? Studies have pointed to glia and other immune cells and their role in pain sensitization that results in cell and sex-specific responses. Using a low-dose and short-term ethanol exposure model, we investigated whether this exposure would sensitize mice to a subthreshold dose of an inflammatory mediator that normally does not induce pain. We observed female mice exhibited specific mechanical and higher thermal sensitivity than males. We also observed an increase in CD68+ macrophages in the ipsilateral dorsal root ganglia (DRG) and Iba1+ microglia in the ipsilateral spinal dorsal horn of animals that were exposed to ethanol and injected with subthreshold inflammatory prostaglandin E2. Our findings suggest that short-term ethanol exposure stimulates peripheral and central, immune and glial activation, respectively to induce pain sensitization. This work begins to reveal a possible mechanism behind the development of alcoholic peripheral neuropathy.
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•Low-dose, short-term alcohol consumption facilitates mechanical allodynia in female but not male mice.•Mechanical allodynia was linked to activated dorsal spinal cord microglia characterized by changes in morphology.•Increased DRG neuronal ATF3 expression and CD68 macrophages were linked to ethanol-induced sensitization in females.