Nociceptive improvements and kynurenine pathway alterations with diclofenac treatment in a rat model of neuropathic pain created by partial sciatic nerve ligation

S. Debbag, A. Yalcinkaya, F. Saricaoglu

Department of Anesthesiology and Reanimation, Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey. ahmety38@gmail.com

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• Pharmacology

OBJECTIVE: Neuropathic pain is regulated by several metabolites of the kynurenine pathway (KYNA-kynurenic acid, and QA-quinolinic acid). Diclofenac exerts analgesic and anti-hyperalgesic effects and also alters KYNA levels, indicating a potential for therapy. We aimed to assess the nociceptive effects of different doses of diclofenac treatment in a rat model of neuropathic pain and to determine potential relationships with KYNA and QA levels (Graphical Abstract).

MATERIALS AND METHODS: Twenty-eight Sprague-Dawley rats were divided into four groups: 40 mg/kg/day diclofenac (high-dose), 20 mg/kg/day diclofenac (normal-dose), non-treatment, and sham. Except for the sham group, the others underwent partial sciatic nerve ligation (left). Baseline (day 0) and post-treatment (day 3) KYNA and QA levels were measured. Allodynia and pain detection were assessed with the von Frey and hot plate tests.

RESULTS: Baseline findings were similar in all groups. Compared to baseline, the non-treatment group had significantly worse allodynia on day 3. Baseline and post-treatment von Frey results (left) remained similar in the normal-dose diclofenac group (p=0.336); however, this benefit was not observed in the high-dose group. Relative to baseline, normal-dose diclofenac recipients had significantly higher KYNA concentration (p=0.046) and KYNA-to-QA ratio (p=0.028) on day 3.

CONCLUSIONS: Our results show that 3-day therapy with 20 mg/kg/day diclofenac can improve nociceptive findings in neuropathic pain, and that this effect may be associated with increased KYNA or KYNA-to-QA ratio. The lack of dose-dependent effects may be associated with potential adverse influences of exceedingly high diclofenac dosage.

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