Controlled-Release Systems in Neuropathic Pain

Abstract

91 ISSN 1758-1869 10.2217/PMT.12.82 © 2013 Future Medicine Ltd Pain Manage. (2013) 3(2), 91–93 Neuropathic pain affects millions of individuals worldwide. Patients with this condition suffer from a variety of symptoms ranging from simple paresthesias to chronic intractable pain. Tricyclic antidepressants, anticonvulsants, GABA analogs and opiates are some of the pharmacological options prescribed [1]. However, mechanism(s) of neuropathic pain are multifaceted, thus making the treatment of pain with any single agent difficult [1]. Conventional treatment for neuropathic pain involves the administration of pain medication by either oral or parenteral route. Systemically administered drugs tend to act on receptors distributed throughout the body, leading to unintended side effects. Drugs routinely administered for neuropathic pain demonstrate significant physical and psychological adverse side effects [2]. Consequently, there has been consid­ erable interest in local therapies, particularly those involving local/regional anesthesia [3,4]. However, the use of nerve blockade to manage neuropathic pain has not received widespread acceptance. Nerve blocks from single­shot injections are themselves painful, are relatively short in duration and pain recurs after the effect of the block subsides [4]. Catheters and pumps can provide prolonged blockade, but these require greater allocation of medical resources and have disadvantages, such as being tethered to a device (in the case of nonimplanted devices) and risk of infection, among others. An alternative approach would use injectable drug delivery systems to provide prolonged duration local anesthesia (PDLA). There is now vast literature reporting a variety of technologies that have been used to release local anesthetics [5]. Typically, those technologies, termed sustained­ (or controlled­) release systems, are injectable matrices that create high tissue concentrations of the drug at the nerve while minimizing systemic distribution. Examples include polymeric microspheres, liposomes, hydrogels and many others. Ideally, although rarely in practice, the rate of release of drugs is constant (‘zero order’). Formulations have been developed that can provide nerve blockade lasting many days in animal models from a single injection [6,7]. PDLA formulations have been used experimentally to prevent the development of neuropathic pain. The physiological rationale for their use is that aberrant neuronal activity from injured primary afferents is believed to be an important contributor to the development of neuropathic pain [8,9]. Excitatory neurotransmitters such as glutamate, released in response to