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Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
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Eukaryotic initiation factor 3d Regulates Context-Dependent Pain Hypersensitivity Through the Integrated Stress
Subhaan M Mian1, Sera I Nakisli1, Brodie J Woodall1
1Center for Advanced Pain Studies and Department of Neuroscience, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080.
Biorxiv : the Preprint Server for Biology
|January 7, 2026
Summary
Eukaryotic translation initiation factor 3 subunit D (eIF3d) deficiency reduces hypersensitivity in stress-induced pain models. However, it may enhance central sensitization, suggesting a context-dependent role in pain processing.
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- Eukaryotic translation initiation factor 3 subunit D (eIF3d) is a noncanonical cap binding protein involved in selective mRNA translation during stress.
- Its role in pain processing remains largely unexplored.
Purpose of the Study:
- To investigate the contribution of eIF3d to pain processing using a heterozygous eIF3d knockout mouse model.
- To determine if eIF3d modulates nociceptive plasticity under various stress conditions.
Main Methods:
- Validation of the eIF3d heterozygous knockout (eIF3d+/-) mouse model by measuring eIF3d mRNA and protein levels.
- Assessment of baseline pain behaviors (mechanical, thermal, cold, spontaneous) in eIF3d+/- and wild-type (WT) mice.
- Evaluation of pain responses in models of peripheral inflammation (methylglyoxal, IL-6, paw incision) and central sensitization (formalin test, EAE).
Main Results:
- eIF3d+/- mice showed significantly reduced mechanical and cold hypersensitivity in inflammation and metabolic stress models.
- Increased second-phase nocifensive behavior in the formalin test was observed in eIF3d+/- mice, suggesting enhanced central sensitization.
- Hyperalgesic priming and EAE induction were comparable between eIF3d+/- and WT mice.
Conclusions:
- eIF3d selectively modulates nociceptive plasticity in response to specific stress conditions.
- The findings suggest a context-dependent role for eIF3d in regulating inflammatory pain and central sensitization.
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