Key result
Adolescent ethanol exposure in rats induces protracted mechanical allodynia and alters prefrontal nociceptive circuit excitability.
Why the study?
Binge drinking is common among adolescents and linked to adverse outcomes including heightened pain perception, but its effects on prefrontal nociceptive circuits were unclear.
Adolescent intermittent ethanol exposure in rats alters synaptic function and intrinsic excitability within a prefrontal nociceptive circuit, promoting mechanical allodynia.
Suggests adolescent alcohol exposure may promote chronic pain via prefrontal circuits; leaves open human relevance.
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.
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Obray et al. (2024) studied Adolescent alcohol exposure / Mechanical allodynia. Adolescent intermittent ethanol (AIE) exposure was evaluated on Mechanical and thermal sensitivity and synaptic function at BLA inputs onto PrL neurons. Adolescent intermittent ethanol exposure in rats induced protracted mechanical allodynia and altered synaptic function and intrinsic excitability within a prefrontal nociceptive circuit.
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