Why is intrathecal drug delivery an attractive option for the treatment of pain?
The dorsal horn of the spinal cord is a major site for pain control. Nociceptive information from the peripheral nervous system is conveyed to the central nervous system by primary afferent neurons. These are primarily myelinated and unmyelinated small-diameter neurons with cell bodies located in the dorsal root ganglia (DRG). The DRG extends central processes through the dorsal roots to synapse on neurons in the superficial and deep laminae of the spinal cord dorsal horn. Inhibitory and facilitatory nociceptive pathways composed of neurons located in the brainstem send axons that descend the neuraxis to synapse on and modulate the function of dorsal horn neurons. Many targets of analgesic drugs (e.g., opioid receptors, voltage-gated calcium channels, adrenergic receptors, and gamma-aminobutyric acid [GABA] receptors) are found in high concentrations in the spinal cord dorsal horn. Consequently, delivery of analgesic drugs directly into the intrathecal space places them in close proximity to their target sites for nociceptive transmission and modulation.