Neuraxial drug delivery in pain management: An overview of past, present, and future

Abstract

Activation of neuraxial nociceptive linkages leads to a high level of encoding of the message that is transmitted to the brain and that can initiate a pain state with its attendant emotive covariates. As we review here, the encoding of this message is subject to a profound regulation by pharmacological targeting of dorsal root ganglion and dorsal horn systems. Though first shown with the robust and selective modulation by spinal opiates, subsequent work has revealed the pharmacological and biological complexity of these neuraxial systems and points to several regulatory targets. Novel therapeutic delivery platforms, such as viral transfection, antisense and targeted neurotoxins, point to disease-modifying approaches that can selectively address the acute and chronic pain phenotype. Further developments are called for in delivery devices to enhance local distribution and to minimize concentration gradients, as frequently occurs with the poorly mixed intrathecal space. The field has advanced remarkably since the mid-1970s, but these advances must always address the issues of safety and tolerability of neuraxial therapy.

Keywords: affective and sensory-dimensions of pain; ascending signaling pathways; cerebrospinal fluid and solute movement; dorsal root ganglion and blood brain barrier; dorsal root ganglion and macrophage; intrathecal and drug distribution; intrathecal and neuropathology; intrathecal and neurotoxins; intrathecal and transfection; pain and nociception.