Binge drinking is common among adolescents despite mounting evidence linking it to various adverse health outcomes that include heightened pain perception. The prelimbic (PrL) cortex is vulnerable to insult from adolescent alcohol exposure and receives input from the basolateral amygdala (BLA) while sending projections to the ventrolateral periaqueductal gray (vlPAG) - two brain regions implicated in nociception. In this study, adolescent intermittent ethanol (AIE) exposure was carried out in male and female rats using a vapor inhalation procedure. Assessments of mechanical and thermal sensitivity revealed that AIE exposure-induced protracted mechanical allodynia. To investigate synaptic function at BLA inputs onto defined populations of PrL neurons, retrobeads and viral labeling were combined with optogenetics and slice electrophysiology. Recordings from retrobead labeled cells in the PrL revealed AIE reduced BLA-driven feedforward inhibition of neurons projecting from the PrL to the vlPAG, resulting in augmented excitation/inhibition (E/I) balance and increased intrinsic excitability. Consistent with this finding, recordings from virally tagged PrL parvalbumin interneurons (PVINs) demonstrated that AIE exposure reduced both E/I balance at BLA inputs onto PVINs and PVIN intrinsic excitability. These findings provide compelling evidence that AIE alters synaptic function and intrinsic excitability within a prefrontal nociceptive circuit.
Keywords: AIE; adolescent alcohol; allodynia; neuroscience; pain; periaqueductal gray; prefrontal cortex; rat.
Alcohol is sometimes used as a temporary form of pain relief. However, heavy and regular consumption can have serious side effects, including altering how the brain processes pain. Over time, this may lead to more frequent and intense episodes of pain, creating a vicious cycle in which individuals drink more to counteract their heightened discomfort. Recent studies in rodents have shown that binge drinking during adolescence also increases sensitivity to pain, with this change often persisting into adulthood. Yet, how alcohol use in teenagers impacts the parts of the brain that process pain remains poorly understood. To investigate this question, Obray et al. compared the brains of adolescent rats that had either been exposed or not exposed to alcohol. The rats were subjected to two types of pain stimuli: mechanical pressure using the end of a metal wire and thermal pain via a heated surface. The team found that less pressure was needed for the alcohol-exposed rats to pull their paws away, suggesting they were more sensitive to pain. However, both groups of rats exhibited similar responses to the heat-related stimulus. Next, Obray et al. explored the connections between the parts of the brain that process pain. A region of the brain known as the prefrontal cortex integrates the sensory and emotional aspects of pain by sending information to and from the amygdala and periaqueductal gray areas. Obray et al. found that inhibitory interneurons in the prefrontal cortex, which may reduce the transmission of pain, were not as well connected to the amygdala in the alcohol-exposed rats. In addition, neurons linking the prefrontal cortex to the periaqueductal gray areas were more excitable in these animals compared to the non-exposed rats. These findings suggest that alcohol use during adolescence may make the brain more reactive to pain while impairing its ability to modulate pain signals. Understanding how early alcohol exposure alters pain sensitivity could help scientists develop strategies that disrupt the harmful cycle between alcohol use and pain. However, further studies are needed to determine whether the effects observed in this study also occur in humans.
© 2024, Obray et al.