Noradrenergic reuptake inhibition in the treatment of pain

Noradrenergic reuptake inhibitors can be effective analgesics, finding application in a wide variety of clinical pain settings. Due to a shift toward noradrenergic-mediated pain pathways following nerve injury, they are particularly well suited to the treatment of neuropathic pain. This phenotypic shift makes neuropathic pain difficult to control with opioids alone; some noradrenergic reuptake inhibitors have demonstrated synergy with opioids. Agents currently in early clinical trials are discussed and include both novel delivery of old drugs and the development of new drugs.

This review was limited to noradrenergic reuptake inhibitors and analgesia. Literature search included the terms adrenergic, noradrenergic, reuptake, inhibitors, analgesia, NET, norepinephrine transporter, and pain using Medline, Google scholar, Web of Knowledge, www.clinicaltrials.gov, and Pharmaprojects (Informa UK Ltd. 2012).

Topical drug delivery and the use of combinations of agents both topically and systemically are under active investigation. The intrathecal delivery of noradrenergic reuptake inhibitors, allowing delivery directly to the central nervous system thus limiting systemic exposure, represents an exciting avenue of investigation. Gaps in current knowledge have complicated the development of prophylactic therapies for susceptible individuals or preemptive intervention. Disease-modifying agents and selective inhibitors would facilitate these treatment strategies.