255) Effects of Cannabinoids on Responses of Human Dorsal Root Ganglia Neurons

Cannabinoids are suggested to be a potentially important alternative approach to analgesia. Rodent models have shown analgesic properties of cannabinoid receptor activation and suppressed nociceptive responses within sensory neurons. The goal of the present study was to determine whether activation of cannabinoid receptors in human sensory neurons could suppress nociceptive responses or hyperactivity. Lumbar level human dorsal root ganglia were recovered from cadaveric organ donors at the University of Cincinnati Medical Center, dissociated and cultured, or fixed and frozen for histology. Using Fura-2AM calcium imaging of viable human sensory neurons, responses to the peripherally active cannabinoid agonist CB-13, a potent CB1/CB2 agonist, in naive neurons were examined. Responses to capsaicin (250 nM) in presence and absence of the inflammatory mediator PGE2 (1 µM) were examined after pre-treatment with 1 µM CB-13, or with CB-13 bath applied in between capsaicin administrations. Our results show that CB-13 produced no calcium influx in sensory neurons on its own, and that responses to capsaicin in naive neurons as well as PGE2-exposed neurons were not altered by CB-13. Patch clamp recordings of human sensory neurons to test changes in membrane properties by cannabinoid receptor activation by CB-13 is reported. Our data do not presently support the concept of peripherally acting cannabinoid receptors as having the capacity to suppress sensory neuron nociceptive responses or sensitization in people.