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.