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

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.

[Changes in alcohol choice by chronically alcoholized cats as affected by tryptopham, its metabolites and preparations affecting its metabolism]. / Izmeneniia vybora alkogolia khronicheski alkogolizirovannymi koshkami pod vliianiem triptofana, ego metabolitov i preparatov, vliiaiushchikh na ego obmen.

In cats unrestrictedly selecting alcohol and water during 5 months - 4.5 years under normal feeding, intraperitoneal injection of 1-tryptophan (5.5 and 65 mg/kg) lowered alcohol intake. Depending on the effect on water intake, a decrease (after a lower dose) or an increase (after a higher dose) in alcohol preference was observed. Tryptophan metabolites (mg/kg): dl-5-hydroxytryptophan (5-HTP, 6 and 12), tryptamine (2.5 and 5), 1-4 and dl-(2 and 6)kynurenine, as well as drugs modifying tryptophan metabolism, such as Ro-4-4602(2), an inhibitor of peripheral decarboxylase of aromatic amino acids, and allopurinol (2), an inhibitor of tryptophan pyrrolase (10 and 17), enhanced alcohol intake. Preference of alcohol was increased after tryptamine and 1-kynurenine and decreased after 5-HTP administration. Control injections of saline and distilled water resulted in a significant increase in alcohol and water intake. Saline increased preference of alcohol.