SPINAL NLRP3 INFLAMMOSOME ACTIVATION AND NON-CODING RNA DYSREGULATION CONTRIBUTE TO MORPHINE-PROLONGED ALLODYNIA IN PRENATAL ALCOHOL-EXPOSED MICE

Author

• Andrea Alejandra Pasmay, University of New MexicoFollow

Publication Date

Summer 7-28-2026

Abstract

Long-term neuroimmune alterations caused by prenatal alcohol exposure (PAE) increase susceptibility to chronic pain. We hypothesized that morphine would synergize with the immune sensitization induced by PAE through Toll-like receptor 4 (TLR4) and NLRP3 inflammasome signaling, prolonging neuropathic pain. Morphine significantly extended allodynia in PAE mice and increased TLR4–NLRP3 inflammatory signaling in the spinal cord, dorsal root ganglia, and injured sciatic nerve. Inhibition of NLRP3 reversed allodynia in both sexes, while TLR4 inhibition was effective in males. We further identified two novel non-coding RNA regulators: miR-433-3p, whose restoration suppressed HMGB1, caspase-1, and IL-1β while reversing allodynia, and circNCOA2, whose selective knockdown reduced TLR4–NLRP3 signaling and relieved pain without affecting its linear transcript. These findings identify promising therapeutic targets for PAE-associated chronic pain.

Keywords

Prenatal alcohol exposure (PAE), Neuropathic pain, Neuroinflammation, TLR4 signaling, Non-coding RNAs (ncRNAs)

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Erin Milligan

Second Committee Member

Shahani Noor

Third Committee Member

Amanda M Barkley-Levenson

Fourth Committee Member

Russell A Morton

Recommended Citation

Pasmay, Andrea Alejandra. "SPINAL NLRP3 INFLAMMOSOME ACTIVATION AND NON-CODING RNA DYSREGULATION CONTRIBUTE TO MORPHINE-PROLONGED ALLODYNIA IN PRENATAL ALCOHOL-EXPOSED MICE." (2026). https://digitalrepository.unm.edu/biom_etds/323