SELECTIVE KILLING OF PAIN NEURONS BY LASER PHOTOLYSIS

THIS PROJECT WILL DEVELOP A CLINICALLY USEFUL PULSED LASER SYSTEM TO PRODUCE HIGHLY SELECTIVE DAMAGE TO PAIN-SENSITIVE NEURONS WITHIN THE DORSAL ROOT (SENSORY) GANGLIA. THE TECHNOLOGY WOULD ALLOW A MINIMALLY INVASIVE THERAPY FOR INTRACTABLE PAIN SYNDROMES ASSOCIATED WITH MALIGNANCY, PERIPHERAL NERVOUS SYSTEM TRAUMA, AND METABOLIC NEUROPATHIES. THIS APPROACH WILL BE AN ALTERNATIVE TO CURRENT NONSELECTIVE NEUROSURGICAL TECHNIQUES. A RECENTLY DEVELOPED LATEX NANOSPHERE DELIVERY SYSTEM WILL BE USED TO LABEL PAIN NEURONS SELECTIVELY WITH CHLORINE E6, A HIGHLY EFFICIENT PRODUCER OF SINGLET OXYGEN, AND DESTROY LABELED NEURONS BY LASER PHOTOLYSIS. STUDIES OF LASER-TISSUE INTERACTION WILL BE INTEGRATED WITH STUDIES OF SELECTIVE NEURONAL TARGETING AND INJURY IN VIVO USING MICE AS THE FIRST EXPERIMENTAL MODEL. NANOSPHERES CARRYING CHLORINE E6 AND A FLUORESCENT LABEL WILL BE INJECTED SUBCUTANEOUSLY INTO MOUSE HIND-LIMB FOOTPADS. THE RATE, LEVEL, AND SPECIFICITY OF UPTAKE FOR SMALL-DIAMETER PAIN NEURONS WILL BE ASSESSED HISTOLOGICALLY. SINGLET OXYGEN GENERATION, ENERGY PENETRATION, AND ENERGY SPATIAL DISTRIBUTION WILL BE QUANTIFIED WITHIN THIS TISSUE. TARGETED PAIN NEURONS WILL BE SELECTIVELY ABLATED INITIALLY WITH SURGICAL EXPOSURE AND, LATER, PERCUTANEOUSLY. IMMEDIATE AND LONG-TERM CELLULAR INJURY WILL BE ASSESSED USING SILVER DEGENERATION AND ROUTINE STAINS.