This research demonstrates a new treatment strategy for chronic pain. It is currently in transition from the lab bench to the patient bedside, as we prepare for a first clinical trial in human subjects. What follows is a personal account of how the research evolved and where it can go in the future. The "paracrine paradigm" we developed is applicable in a general fashion to therapy for chronic neurological disorders.
Pain: Study It or Treat It?
This work began in the summer of 1993 with a small program in therapeutics"small because I was able to carve out only limited time over two summers with an HHMI high school student, Susan Lee (who has since gone on to Harvard Medical School in Boston). I had always been a basic bench scientist, and my lab had been studying synaptic-induced gene regulation in the spinal cord in models of persistent peripheral inflammation. I had discovered that persistent pain up-regulates the opioid peptide dynorphin in the dorsal spinal cord, the first synaptic processing station for pain"first observing this with a radioimmunoassay for dynorphin peptide and later measuring the corresponding mRNA increases, performing studies to localize the spinal neurons involved, and eventually examining seven base pairs of enhancer sequence in the promoter.
