Analgesic activity of the novel COX-2 preferring NSAID, meloxicam in mono-arthritic rats: central and peripheral components.

OBJECTIVE AND

DESIGN

To study the characteristics and site of the analgesic action of meloxicam.

SUBJECTS: Adult female Wistar rats.

TREATMENT: Monoarthritis was induced (for behavioural studies) by injection of complete Freund's adjuvant into the ankle. Meloxicam was given for 5 days (0.1-4 mg/kg/ day i.p.). Inflammation of the knee or paw (for electrophysiology) was induced with carrageenan. Meloxicam was given i.v. (4-64 mg/kg).

METHODS

Rats were tested daily for joint hyperalgesia, and hindlimb posture (behaviour). At post-mortem, joint stiffness, oedema and gastric lesions were assessed. In anaesthetised rats, nociceptive reflex responses to stimulation of the paw were compared (electrophysiology). Statistics were performed using one-way analysis of variance.

RESULTS

Meloxicam reduced swelling and stiffness of the inflamed joint, joint hyperalgesia (ID50 = 0.4 +/- 0.4 mg/kg/ day) and spontaneous pain-related behaviour. It also inhibited peripherally mediated reflex responses to stimulation of inflamed tissue (ID50 = 7.6 +/- 0.8 mg/kg.i.v.) without affecting centrally mediated reflexes.

CONCLUSIONS

Systemic meloxicam produces analgesia largely via peripheral mechanisms. The rapidity of its actions indicates a direct effect on sensitised nociceptors.