biostudies-literatureUnknownPasmay AANIAAA NIH HHSNIGMS NIH HHSAdverse in-utero conditions may exert a lifelong impact on neuroimmune function. Our prior work showed that prenatal alcohol exposure (PAE) increases pathological pain sensitivity (allodynia) following peripheral sciatic nerve injury. While the immune mechanism(s) of PAE-induced immune dysfunction are poorly understood, prior studies implicated the involvement of Toll-like receptor 4 (TLR4) and the nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasomes. Interestingly, emerging data suggest a surprising overlap of spinal glial proinflammatory activation via the TLR4-NLRP3-interleukin (IL)-1β axis due to opioid treatment in nerve-injured non-PAE rodents. Considering this preclinical evidence, we explored whether PAE poses a risk factbioRxiv : the preprint server for biology2025.05.30.655639https://www.ebi.ac.uk/biostudies/studies/S-EPMC12154580biostudies-literaturePrenatal alcohol exposure promotes nerve injury-induced pathological pain following morphine treatment via NLRP3-mediated peripheral and central proinflammatory immune actions.PMC12154580T34 GM145428P20 GM121176P50 AA022534R01 AA025967R01 AA029694Pasmay AACarter JMurphy MPritha ANFernandez-Oropeza AKJones AJimenez DCNoor SSun MSValenzuela CFfalsePrenatal alcohol exposure promotes nerve injury-induced pathological pain following morphine treatment via NLRP3-mediated peripheral and central proinflammatory immune actions.Adverse in-utero conditions may exert a lifelong impact on neuroimmune function. Our prior work showed that prenatal alcohol exposure (PAE) increases pathological pain sensitivity (allodynia) following peripheral sciatic nerve injury. While the immune mechanism(s) of PAE-induced immune dysfunction are poorly understood, prior studies implicated the involvement of Toll-like receptor 4 (TLR4) and the nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasomes. Interestingly, emerging data suggest a surprising overlap of spinal glial proinflammatory activation via the TLR4-NLRP3-interleukin (IL)-1β axis due to opioid treatment in nerve-injured non-PAE rodents. Considering this preclinical evidence, we explored whether PAE poses a risk fact2025-01-01T00:00:00Z2025 May2026-06-03T03:13:25.843Z2026-06-03T03:10:38.812ZS-EPMC121545804050183210.1101/2025.05.30.655639