PMID- 24769167 OWN - NLM STAT- MEDLINE DCOM- 20141215 LR - 20161125 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1566 DP - 2014 May 30 TI - Chemical stimulation of the intracranial dura activates NALP3 inflammasome in trigeminal ganglia neurons. PG - 1-11 LID - S0006-8993(14)00517-4 [pii] LID - 10.1016/j.brainres.2014.04.019 [doi] AB - Inflammasomes are molecular platforms that upon activation by cellular infection or stress trigger the maturation of proinflammatory cytokines such as interleukin (IL)-1beta to engage innate immune defenses. Increased production of IL-1beta 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-1beta. Chemical stimulation of the intracranial dura caused a total drug dose- and time-dependent induction of activated caspase-1 and mature IL-1beta proteins. Application of a selective caspase-1 inhibitor diminished these effects. Immunohistochemistry revealed that both NALP3 inflammasome and IL-1beta 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-1beta, 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-1beta maturation in the TG. This may contribute to strategies for headache control. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Chen, Lingzhi AU - Chen L AD - Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, PR China. FAU - Li, Xiaohui AU - Li X AD - Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, PR China. FAU - Huang, Lin AU - Huang L AD - Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, PR China. FAU - Wu, Qian AU - Wu Q AD - Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, PR China. FAU - Chen, Ling AU - Chen L AD - Department of Physiology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, PR China. FAU - Wan, Qi AU - Wan Q AD - Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, PR China. Electronic address: qi_wan@126.com. LA - eng PT - Journal Article DEP - 20140423 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Carrier Proteins) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, rat) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Animals MH - Carrier Proteins MH - Caspase 1/metabolism MH - Disease Models, Animal MH - Dura Mater/drug effects/*metabolism MH - Headache/*metabolism MH - Inflammasomes/*metabolism MH - Inflammation/metabolism MH - Interleukin-1beta/metabolism MH - Male MH - NLR Family, Pyrin Domain-Containing 3 Protein MH - Neurons/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Cytoplasmic and Nuclear/*metabolism MH - Stimulation, Chemical MH - Trigeminal Ganglion/*metabolism OTO - NOTNLM OT - Caspase-1 OT - Dural inflammation OT - Headache OT - Interleukin-1beta OT - NALP3 inflammasome OT - Trigeminal Ganglion EDAT- 2014/04/29 06:00 MHDA- 2014/12/17 06:00 CRDT- 2014/04/29 06:00 PHST- 2014/01/09 00:00 [received] PHST- 2014/04/11 00:00 [revised] PHST- 2014/04/12 00:00 [accepted] PHST- 2014/04/29 06:00 [entrez] PHST- 2014/04/29 06:00 [pubmed] PHST- 2014/12/17 06:00 [medline] AID - S0006-8993(14)00517-4 [pii] AID - 10.1016/j.brainres.2014.04.019 [doi] PST - ppublish SO - Brain Res. 2014 May 30;1566:1-11. doi: 10.1016/j.brainres.2014.04.019. Epub 2014 Apr 23.