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Updated: May 31, 2026
07:12
Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
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, United States.
Neurobiology of Pain (Cambridge, Mass.)
|May 29, 2026
Summary
Eukaryotic translation initiation factor 3 subunit D (eIF3d) plays a role in stress-induced pain. Mice lacking one eIF3d copy showed reduced hypersensitivity in some pain models but not others, indicating a context-dependent function.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Eukaryotic translation initiation factor 3 subunit D (eIF3d) is a noncanonical cap-binding protein involved in 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 understand the specific mechanisms by which eIF3d influences nociceptive plasticity under various stress conditions.
Main Methods:
- Validation of a heterozygous eIF3d knockout (eIF3d+/-, HET) mouse model.
- Assessment of basal nociception and hypersensitivity in response to inflammatory (carrageenan, IL-6, formalin) and metabolic (methylglyoxal) stressors.
- Evaluation of pain behaviors in an experimental autoimmune encephalomyelitis (EAE) model.
- Measurement of eIF2α phosphorylation in dorsal root ganglia (DRG) tissue.
Main Results:
- HET mice showed reduced mechanical and cold hypersensitivity in response to inflammation and metabolic stress.
- Increased second-phase nocifensive behaviors in the formalin test were observed in HET mice, suggesting potential central sensitization.
- IL-6-induced eIF2α phosphorylation and downstream Integrated Stress Response (ISR) activation in DRG were attenuated in HET mice.
- EAE-induced motor deficits and pain hypersensitivity were not affected in HET 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 and central pain sensitization.
- eIF3d may represent a potential therapeutic target for specific pain conditions.
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