Synergistic antiallodynic effects of pregabalin and thioctic acid in a rat model of neuropathic pain.

Background: Neuropathic pain is a chronic and often disabling condition that remains refractory to monotherapy because of limited efficacy and dose-limiting adverse effects. Combination therapies that engage complementary mechanisms of action offer a rational strategy to enhance efficacy while minimizing toxicity. Pregabalin, a ligand of α Methods: We evaluated the antiallodynic efficacy of pregabalin and thioctic acid, alone and in combination, in female Wistar rats subjected to L5-L6 spinal nerve ligation. Mechanical withdrawal thresholds were measured using von Frey filaments up to 8 h post-oral administration. Dose-response curves were generated for each monotherapy and its 1:1 fixed-ratio combination. Isobolographic analysis was conducted to quantify pharmacodynamic interactions. All behavioural testing was performed under blinded conditions, and adverse effects were qualitatively monitored. Results: Both compounds produced dose-dependent increases in mechanical withdrawal thresholds (antiallodynic effects), with ED Conclusion: These findings provide robust preclinical evidence that co-administration of pregabalin and thioctic acid produces synergistic antiallodynic effects in a validated model of neuropathic pain. This interaction enables effective analgesia at reduced doses, supporting a potential tolerability advantage. Our data support further investigation of this combination in chronic dosing paradigms, inclusion of both sexes, and clinical translation.