HMGB1 released from nociceptors mediates inflammation

• Nociceptors are sensory neurons that detect changes in the body’s internal and external milieu. Although occupying a primary role in signaling these changes to the nervous system, nociceptors also initiate neurogenic inflammation by sending antidromic signals back into the tissue. Because HMGB1 is a well-characterized endogenous mediator, which stimulates inflammation and is expressed by neurons, we reasoned HMGB1 release may be an important component of neurogenic inflammation. Here, by combining optogenetics, neuronal-specific ablation, nerve-injury, and inflammatory disease models, with direct assessment of inflammation and neuropathic pain, we show that nociceptor HMGB1 is required for an inflammatory response. These results provide direct evidence that nociceptor-related pain and inflammation can be prevented by targeting HMGB1.

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