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 ana lgesic action of meloxicam. Subjects: Adult female Wistar rats. Treatm ent: Monoarthritis was induced (for behavioural studies', by injection of complete Freund's adjuvant into the ankle. Meloxicam was given for 5 days (0.1-4mg/kg/day i.p.). Inflammation of the knee or paw (for el ectrophysiology) 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, o edema and gastric lesions were assessed. In anaesthetised rats, nocice ptive reflex responses to stimulation of the paw were compared (electr ophysiology). Statistics were performed using one-way analysis of vari ance. Results: Meloxicam reduced swelling and stiffness of the inflame d joint, joint hyperalgesia (ID50 = 0.4 +/- 0.4 mg/kg/day) and spontan eous pain-related behaviour. It also inhibited peripherally mediated r eflex responses to stimulation of inflamed tissue (ID50 = 7.6 +/- 0.8 mg/kg i.v.) without affecting centrally mediated reflexes. Conclusion: Systemic meloxicam produces analgesia largely via peripheral mechanis ms. The rapidity of its actions indicates a direct effect on sensitise d nociceptors.