Peripheral opioid analgesia for the treatment of neuropathic pain: Gene mutation to virus mediated gene transfer

Neuropathic pain can result from a number of different diseases, medical interventions and injuries. In addition to varying aetiologies, neuropathic pain may also differ in the anatomical location of the lesion - from peripheral nociceptors to the highest centres in the brain. The management of neuropathic pain continues to be a challenge for clinicians and despite taking prescribed medication for pain, patients with neuropathic pain continue to have pain of moderate severity. The use of opioids for the treatment of chronic neuropathic pain remains controversial. Recent studies demonstrate opioid analgesics are effective in neuropathic pain states but their use is often limited by unacceptable side effects that are mediated by opioid actions in the central nervous system. While it was once dogma that opioids exert their analgesic effects by binding to receptors in the central nervous system, there is a growing recognition of a potent peripheral analgesia in experimental models of inflammatory and neuropathic pains, and in clinical settings. The working model is that peripheral opioids can be used to treat neuropathic pain while avoiding the often dose-limiting and unacceptable central nervous system mediated side effects. Our work has focused on characterizing this peripheral opioid analgesia such that it can be exploited to develop novel and potent peripheral analgesics for the treatment of neuropathic pain. This article will set the clinical stage for the need for novel treatments for neuropathic pain, the use of gene mutation strategies to make the case for the use of opioids in treating neuropathic pain, the demonstration of peripheral opioid analgesia in neuropathic pain, and our work with virus mediated gene transfer to enhance peripheral opioid analgesia in neuropathic pain.