Inflammasomes are molecular platforms that upon activation by cellular infection or stress trigger the maturation of proinflammatory cytokines such as interleukin (IL)-1β to engage innate immune defenses. Increased production of IL-1β in pain and inflammation such as headache is well documented. However, limited evidence addresses the participation of inflammasomes in inflammatory pain. The present study used rat inflammatory dural stimulation-induced model of intracranial pain to assess whether headache-related pain can induce the activation of NACHT, LRR, and PYD-containing protein (NALP)-3 inflammasome pathway in the trigeminal ganglia (TG) and which cells express NALP3 inflammasome proteins and IL-1β. Chemical stimulation of the intracranial dura caused a total drug dose- and time-dependent induction of activated caspase-1 and mature IL-1β proteins. Application of a selective caspase-1 inhibitor diminished these effects. Immunohistochemistry revealed that both NALP3 inflammasome and IL-1β immunoreactivity were existed mainly in small to medium-sized C-type neurons and increased over time, with intense cytoplasmic staining after 3 days of dural inflammation. Overall, the present observation indicated that dural inflammation promoted assembly of the multiprotein NALP3 complex, activated caspase-1, and induced processing of IL-1β, which provides an indirect evidence of the participation of NALP3 inflammasome in the cascade of events involved in the genesis of headaches by promoting IL-1β maturation in the TG. This may contribute to strategies for headache control.
Keywords: Caspase-1; Dural inflammation; Headache; Interleukin-1β; NALP3 inflammasome; Trigeminal Ganglion.
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