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 alpha 2-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 micrograms 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 micrograms 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.

α2‐Agonists as analgesic agents

“…28 Moreover, intra-articular administration of a low dose of an a 2 -adrenoceptor agonist significantly attenuated postoperative pain by surgery of the knee joint in humans. 29 In arthritic mice, a knockout of the a 2A -adrenoceptor or intraarticular, but not intrathecal administration of an a 2 -adrenoceptor antagonist, reversed the antihyperalgesic effect induced by transcutaneous electrical stimulation: 30 this finding suggests that the a 2A -adrenoceptor is involved in mediating the pain suppressive effect induced by transcutaneous electrical stimulation. It has been hypothesized that release of opioids from cutaneous immune cells may be mediating pain suppressive effect of norepinephrine in the inflamed skin of rats.…”

Topical and Peripherally Acting Analgesics

“…Both an intrinsic analgesia (Gentili et al, 1996; and augmentation of analgesia produced by bupivacaine (Reuben and Connelly, 1999;Joshi et al, 2000) and morphine (Buerkle et al, 2000) have been reported. Clonidine has been injected into the inflamed knee joint of rodents in preclinical trials, and analgesia was observed to be enhanced by inflammation .…”

Comparison of nebulized ketamine and ketamine with clonidine in postoperative sore throat

“…[13][14][15] Various preclinical and clinical studies have reported that clonidine produces antinociception regardless of the route of administration (central or peripheral). [16][17][18][19] Topical administration of clonidine elicits antinociception by blocking the emerging pain signals at peripheral terminals through alpha 2 adrenoceptors without producing the undesirable central side effect observed after systemic administration. 20 In a dose response study, it was demonstrated that iv clonidine 3µg/kg was more effective than clonidine 2µg/kg for postoperative pain relief after hemilaminectomy, while clonidine 5µg/kg resulted in same analgesia with significant side effects.…”