Epidural clonidine analgesia for intractable cancer pain

Abstract

Although the vast majority of patients with cancer pain receive effective analgesia from standard therapy, a few patients, particularly those with neuropathic pain, continue to experience severe pain despite large doses of systemic or intraspinal opioids. Animal studies suggest intraspinal alpha 2-adrenergic agonists may be effective in such cases. Eighty-five patients with severe cancer pain despite large doses of opioids or with therapy-limiting side effects from opioids were randomized to receive, in a double-blind manner, 30 micrograms/h epidural clonidine or placebo for 14 days, together with rescue epidural morphine. Pain was assessed by visual analog score (VAS), McGill Pain Questionnaire, and daily epidural morphine use. Success was defined as a decrease in either morphine use of VAS pain, with the alternative variable either decreasing or remaining constant. Blood pressure, heart rate, and degree of nausea and sedation were monitored. Successful analgesia was more common with epidural clonidine (45%) than with placebo (21%). This was particularly prominent in those with neuropathic pain (56% vs. 5%). Pain scores were lower at the end of the treatment period in patients with neuropathic pain treated with clonidine rather than placebo, whereas morphine use was unaffected. Clonidine, but not placebo, decreased blood pressure and heart rate. Hypotension was considered a serious complication in 2 patients receiving clonidine and in 1 patient receiving placebo. This study confirms the findings from previous animal studies which showed the effective, potent analgesic properties of intraspinal alpha 2-adrenergic agonists and suggests that epidural clonidine may provide effective relief for intractable cancer pain, particular of the neuropathic type.

Descending pain modulation and chronification of pain

“…In contrast to the spinal α 2 -adrenergic receptors, activation of spinal α 1 -adrenergic receptors shows a pain facilitatory effect [92]. Spinal administration of α 2 -adrenergic agonists produce analgesia in humans as well [93,94]. …”

Evaluation of Antinociceptive and Neurotoxic Effects of Intrathecal Dexmedetomidine in Rats

“…After demonstration of alpha 2 -adrenoceptors in the dorsal horn of the spinal cord and in multiple areas of the brain, alpha 2 -adrenergic agonists, such as clonidine and dexmedetomidine, have been used spinally and systemically to produce antinociceptive effects in different pain modalities in animals and humans (11,12). Dexmedetomidine exerts its antinociceptive actions in the spinal cord by hyperpolarizing the membrane potentials of substantia gelatinosa neurons by activation of K + channels through α 2A -and α 2C -adrenoceptors (13).…”

Emerging drugs for neuropathic pain

“…Side effects were mild and transient and did not result in any patient discontinuing therapy. The largest study to date was published by Eisenach et al who used a double-blind placebo-controlled trial of epidural clonidine for the management of cancer pain [67]. They used epidural morphine as a rescue.…”

“…This will certainly result in many new analgesics in the coming years. [90] + [62,67] + [22] + [65] NMDA antagonists + [91] + [92] + [57] + [93] + [94] + [95] 0 [96] + [97] 0 [98] NSAIDs + [70] 0 [71] 0 [71] + [57] Na + channel antagonists [99] 0 [100] + [101] 0 [102] Ca + channel antagonists + [39] + [55] + [59] + [39] + [60] Adenosine agonists + [76] + [75] + [78] + [82] Neuropeptide antagonists + [103] …”