BACKGROUND/AIMS: Pruritus, also known as itch, is a common, unpleasant sensation that can be difficult to treat. Frequently, chronic itch is associated with the development of neuropathic pain resulting from nerve injury or insult. Previous studies have shown the involvement of spinal microglia in the development of neuropathic pain, but their role in chronic pruritus is unclear. METHODS: For this study, we constructed a model of chronic pruritus in mice using repeated applications of 2, 4-dinitrofluorobenzene (DNFB) and showed prolonged scratching behavior in treated mice that continued for at least 7 d after the final DNFB treatment. RESULTS: Scratching was accompanied by activation of spinal microglia and both were reduced by an inhibitor of microglial activity. We also showed that microglial activation entailed increased signaling in the p38 MAPK pathway, and treatment with a p38 inhibitor reduced scratching in DNFB-treated mice. We also examined the role of fractalkine/CX3CR1 signaling in the development of DNFB-induced pruritus and showed that intrathecal administration of antiserum against either CX3CR1or FKN inhibited p38 activity and decreased scratching. CONCLUSION: Our results suggest that microglia are involved in pruritus induced by DNFB via FKN/CX3CR1/p38MAPK pathways similar to those participating in the development of neuropathic pain.
BACKGROUND/AIMS: Pruritus, also known as itch, is a common, unpleasant sensation that can be difficult to treat. Frequently, chronic itch is associated with the development of neuropathic pain resulting from nerve injury or insult. Previous studies have shown the involvement of spinal microglia in the development of neuropathic pain, but their role in chronic pruritus is unclear. METHODS: For this study, we constructed a model of chronic pruritus in mice using repeated applications of 2, 4-dinitrofluorobenzene (DNFB) and showed prolonged scratching behavior in treated mice that continued for at least 7 d after the final DNFB treatment. RESULTS: Scratching was accompanied by activation of spinal microglia and both were reduced by an inhibitor of microglial activity. We also showed that microglial activation entailed increased signaling in the p38 MAPK pathway, and treatment with a p38 inhibitor reduced scratching in DNFB-treated mice. We also examined the role of fractalkine/CX3CR1 signaling in the development of DNFB-induced pruritus and showed that intrathecal administration of antiserum against either CX3CR1or FKN inhibited p38 activity and decreased scratching. CONCLUSION: Our results suggest that microglia are involved in pruritus induced by DNFB via FKN/CX3CR1/p38MAPK pathways similar to those participating in the development of neuropathic pain.