Multimodal combinations of diclofenac with central adjuvants in adjuvant arthritis: effects on mechanical hyperalgesia and central sensitisation

Background/Aim: Chronic inflammatory pain is a complex multifactorial condition involving sustained immune, neuronal and glial activation, with persistent alterations in both peripheral and central nociceptive processing. Aim of the study was to investigate the antinociceptive efficacy of diclofenac sodium alone and in combination with centrally acting adjuvants in a rat model of adjuvant arthritis. Methods: Adjuvant arthritis was induced in male rats using complete Freund's adjuvant. Animals were allocated to six groups: intact control, untreated arthritis, diclofenac monotherapy and diclofenac combined with gabapentin, pregabalin or amitriptyline. Treatment was administered from day 14 to day 28. Mechanical nociceptive thresholds were assessed using the Randall-Selitto test. Results: Adjuvant arthritis caused a marked reduction in mechanical nociceptive threshold by day 14. By day 28, diclofenac monotherapy partially restored pain thresholds, whereas combinations with gabapentin and pregabalin produced significantly greater recovery compared with diclofenac alone. The amitriptyline combination showed a moderate effect that did not reach conventional statistical significance. These findings indicate a greater contribution of central mechanisms in the later phase of inflammatory pain. Conclusions: Diclofenac-based multimodal therapy, particularly in combination with gabapentinoids, provides superior antinociceptive efficacy compared with NSAID monotherapy in chronic inflammatory pain. These findings support the relevance of targeting both peripheral and central mechanisms in persistent arthritis-related hyperalgesia.