Chemical stimulation of the intracranial dura activates NALP3 inflammasome in trigeminal ganglia neurons.
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.
Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, PR China.
Lingzhi
L
Chen
Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, PR China.
Xiaohui
X
Li
Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, PR China.
Lin
L
Huang
Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Street, Nanjing, Jiangsu Province 210029, PR China.
Qian
Q
Wu
Department of Physiology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, PR China.
Ling
L
Chen
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.
Qi
Q
Wan
D000818:Animals; D002352:Carrier Proteins; D020170:Caspase 1 / Q000378:metabolism; D004195:Disease Models, Animal; D004388:Dura Mater / Q000187:drug effects / Q000378:metabolism*; D006261:Headache / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013268:Stimulation, Chemical; D012668:Trigeminal Ganglion / Q000378:metabolism*
D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D020170:Caspase 1
Caspase-1; Dural inflammation; Headache; Interleukin-1β; NALP3 inflammasome; Trigeminal Ganglion