Amygdala circuits mediate adolescent alcohol exposure effects on pain

The National Institute on Alcohol Abuse and Alcoholism awarded Louisiana State University Health Sciences Center New Orleans $158,600 on November 3, 2026, under the Alcohol Research Programs (CFDA 93.273) to conduct research identifying the mechanisms underlying alcohol-induced hyperalgesia in adult rats. The project period runs through August 31, 2028, with work performed in New Orleans, Louisiana.

The award funds experimental research examining how chronic adolescent alcohol exposure produces lasting pain sensitivity in adulthood and the role of amygdala circuits in mediating this effect. The research tests the hypothesis that chronic adolescent alcohol exposure produces persistent hyperalgesia in male and female rats and identifies the underlying neuroplastic mechanisms, focusing on glutamatergic transmission onto midbrain-projecting central amygdala cells and their relationship to adult pain sensitivity.

Abstract

The number one cause of disability in adults in the united states is chronic pain with upwards of 100 million people reporting chronic pain in their lifetime, prompting the institute of medicine to label chronic pain as a major public health CONCERN10-13. Acute alcohol use is analgesic in HUMANS51, and IT is estimated that 20-50% of adults in the united states that suffer from chronic pain use alcohol to self-MEDICATE20-21. Additionally, chronic use causes people to develop tolerance to the acute analgesic effects of alcohol, and cessation of chronic alcohol use leads to hyperalgesia, thus further promoting the consumption of ALCOHOL16. Adolescence is a critical period of brain development characterized by significant hormonal, physiological, behavioral and neurochemical changes, as well as impaired decision making and increased risk taking, which includes experimentation with drugs and alcohol. Adolescent alcohol use is a strong predictor for the development of alcohol use disorder (AUD) later in life and neuroadaptations produced by early alcohol use drive the onset and progression of AUD. Little is known regarding the specific neuroplastic events that underlie hyperalgesia after chronic alcohol exposure during adolescence or adulthood, but this field of study is growing. Recently published work from our lab shows that a history of chronic intermittent alcohol exposure during adolescence (AIE) leads to a reduction in excitatory (i.e., glutamatergic) transmission onto midbrain-projecting central amygdala cells, and that lower activity of this circuit is linked to higher pain sensitivity in ADULTHOOD1. Here, we propose a set of experiments that focus on identifying the mechanisms underlying AIE-induced hyperalgesia in adult rats. Our overall hypothesis is that chronic adolescent alcohol exposure produces lasting hyperalgesia in male and female rats that persists into adulthood, and this effect is mediated by reductions in synaptic drive from basolateral amygdala (BLA) glutamate neurons onto midbrain-projecting neurons in the medial aspect of the central amygdala (CEM). Specifically, we will test the predictions that AIE reduces neuronal activity of BLA neurons that project to CEM, reduces glutamate release from BLA terminals onto midbrain-projecting CEM neurons, and that hyperalgesia after AIE is mediated by reduced activity in this BLA-CEA-midbrain circuit. To test these predictions, we will expose male and female wistar rats to chronic intermittent alcohol during adolescence, then use a combination of molecular biology, slice electrophysiology and circuit-based approaches to measure specific outcomes. This fellowship will provide the applicant with technical training and professional development skills that will be essential for his career goals of submitting a competitive K99/R00 application, moving onto an independent career at the intersection of alcohol research and epilepsy, and securing a tenure-track faculty research position.