Figure 2.

Schematic diagram of gene therapy strategies for IC/PBS. Gold particles coated with POMC or PPE DNA were used to bombard the bladder wall. These plasmid DNAs encode the peptides (POMC and PPE) that can only locally block pain by suppressing further neuropeptide release. HSV vectors expressing either the PPE gene (HSV-PPE) or the lacZ control (HSV-lacZ) are injected into bladder wall where viral genomes can encode enkephalins locally and virus can be transported to bladder afferent pathways. In contrast to using gold particles with the gene gun technology, HSV-PPE vector genomes present within L6-S1 DRG bladder afferents synthesize and release enkephalins within the dorsal horn of spinal cord, and binding of met- and leu-enk to opioid receptors present on postsynaptic second-order spinal tract neurons and presynaptic bladder afferents may allow better suppression of synaptic transmission of the bladder pain responses. DRG, dorsal root ganglia; HSV, herpes simplex virus; IC/PBS, interstitial cystitis/painful bladder syndrome; POMC, pro-opiomelanocortin; PPE, preproenkephalin.