Alpha2-adrenoceptor agonists in the management of chronic pain

The rationale and potential use of α2-agonists in the management of chronic pain is discussed, along with a review of the literature. Most published reports describe the spinal or epidural administration of clonidine. The oral administration of α2-agonists such as tizanidine has also proved effective in the management of spinal spasticity. Pre-clinical data suggests that spinal α2-agonists may be a useful alternative when spinal opioid tolerance develops because of the relative lack of cross-tolerance between these two drug classes. The published experience with chronic neuraxial administration of α2-agonists is limited to a few studies of chronic epidural administration in cancer patients and some case reports of chronic intrathecal administration in non-cancer pain patients. Approved in the USA for epidural administration in cancer patients with intractable pain, the epidural administration of clonidine appears to be safe given the lack of reported toxicity in animals and in human bolus dose studies. There is still, however, a lack of clinical data to assess toxicity during chronic intrathecal infusion. The principal advantages of clonidine over spinal morphine appear to be its potential, efficacy in some neuropathic pain states, a different side-effect profile and a lack of cross-tolerance to morphine. Further clinical studies are required to explore further its potential in this regard and establish a lack of toxicity during chronic intrathecal administration.