Abstract Details

Title Assessment of the Role of Aldehyde Dehydrogenase-2 in Nociception in a Mice Model of Complex Regional Pain Syndrome Type I

Topic Pain

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 14-002

Objective This study aims to investigate the role of ALDH-2 in a CRPS-I model in mice following treatment with Alda-1.

Background Complex regional pain syndrome type I (CRPS-I) is a disabling condition triggered by ischemia and reperfusion after physical injury. Tissue damage releases reactive substances such as 4-hydroxy-2-nonenal (4-HNE), linked to pain in CRPS-I through TRPA1 activation. The enzyme aldehyde dehydrogenase-2 (ALDH-2) metabolizes 4-HNE, but its role in CRPS-I remains unclear. Alda-1, an ALDH-2 activator, has shown analgesic effects in ischemia models.

Design/Methods C57BL/6 mice (UFSM; 4736260620) were evaluated for baseline mechanical and cold allodynia, rotarod performance, and body weight prior to osmotic minipump implantation. Chronic post-ischemia pain (CPIP) was induced by applying an elastic tourniquet to the right hind paw for two hours to promote ischemia followed by reperfusion. Mice were then treated with Alda-1 or vehicle (16 mg/kg) for 15 days via osmotic minipump. Behavioral assessments were performed daily, and nest building was analyzed between the 15th and 16th days. The 4-HNE protein adducts and NADPH oxidase enzyme in the dorsal horn of the spinal cord (DHSC; L3-L5), spinal cord, and nerve sciatic were assessed.

Results Mice receiving vehicle exhibited marked mechanical, cold allodynia compared to controls, whereas Alda-1 treatment significantly reduced both pain responses throughout the experiment. No alterations in body weight or locomotor activity were observed. Additionally, Alda-1 preserved nest building behavior, which was reduced in CPIP-vehicle animals, indicating potential antinociceptive and neuroprotective effects. Alda-1 treatment significantly reduced 4-HNE protein adduct levels, whereas NADPH oxidase (NOX) expression remained unchanged.

Conclusions

The results of our study indicate a promising approach for CRPS-I. ALDH-2 activation by Alda-1 significantly attenuated nociception, associated with reduced 4-HNE levels. Our findings suggest that ALDH-2 activation may be an alternative for pain management in CRPS-I and other ischemic diseases.

Authors/Disclosures
Julia Maria Frare PRESENTER	Julia Maria Frare has nothing to disclose.
Patrícia Rodrigues, PhD	Dr. Rodrigues has nothing to disclose.
Fernanda T. Tibolla Viero	Dr. Tibolla Viero has nothing to disclose.
Diulle S. Peres, Sr., PhD	Mrs. Peres has nothing to disclose.
Náthaly Andrighetto	Mrs. Andrighetto has nothing to disclose.
Vanessa O. Zambelli, PhD	Mrs. Zambelli has nothing to disclose.
Gabriela T. TREVISAN, PhD	Prof. TREVISAN has nothing to disclose.

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