Peripheral analgesic effect of intra-articular clonidine

Abstract

Sympathetic nervous system stimulation, which releases noradrenaline, influences the nociceptor activity which develops after tissue injury. The a2-adrenergic agonist, clonidine, produces analgesia through a central mechanism but also inhibits noradrenaline release at terminal nerve fibre endings. Clonidine may induce analgesia when administered at peripheral sites. This study assesses the potential analgesic effect of clonidine after intra-articular administration. Forty ASA I-III patients, scheduled for arthroscopic knee surgery under general anaesthesia were allocated randomly in 4 groups of 10 patients each, at the end of the surgical procedure. In the control group (group 1), the patients received 20 ml of intra-articular isotonic saline. In group 2, the patients received 150 μg of clonidine diluted in 20 ml of isotonic saline injected into the knee joint. In group 3, the patients were given 20 ml of intra-articular isotonic saline and clonidine 150 μg was injected subcutaneously. In group 4, morphine 1 mg, diluted in 20 ml of isotonic saline, was injected into the knee joint. Postoperative pain was assessed in a double-blind fashion using a visual analogue scale (VAS) at 1, 2, 3, 6 and 24 h after the end of surgery. VAS scores were significantly lower in groups 2 and 4, compared to groups 1 and 3, at 1 and 2 h after surgery. The delay between intra-articular injection and further postoperative analgesic administration was significantly longer ( P < 0.05) in group 2 (533 ± 488 min) compared to groups 1 and 3 (70 ± 30 min and 132 ± 90 min, respectively). The difference was not significant between group 4 (300 ± 419 min) and the other groups. We conclude that a low dose of intra-articular clonidine produces analgesia unrelated to vascular uptake of the drug. This study further supports a peripheral analgesic effect of clonidine.