Meningeal transient receptor potential channel M8 activation causes cutaneous facial and hindpaw allodynia in a preclinical rodent model of headache

被引:49
作者
Burgos-Vega, Carolina C. [1 ]
Ahn, David Dong-Uk [1 ]
Bischoff, Christina [1 ]
Wang, Weiya [2 ]
Horne, Dan [2 ]
Wang, Judy [2 ]
Gavva, Narender [2 ]
Dussor, Gregory [1 ,3 ]
机构
[1] Univ Arizona, Dept Pharmacol, Tucson, AZ 85721 USA
[2] Amgen Inc, Thousand Oaks, CA USA
[3] Univ Texas Dallas, Sch Behav & Brain Sci, JO 4-208 800 W Campbell Rd, Richardson, TX 75083 USA
基金
美国国家卫生研究院;
关键词
Transient receptor potential channel M8; headache; dura; migraine; allodynia; cold; sumatriptan; TRPM8-EXPRESSING SENSORY NEURONS; OXIDE SYNTHASE INHIBITION; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; ION CHANNELS; DURAL AFFERENTS; COMMON MIGRAINE; TRP CHANNEL; COLD; REPLICATION;
D O I
10.1177/0333102415584313
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Migraine headache is a neurological disorder affecting millions worldwide. However, little is known about the mechanisms contributing to migraine. Recent genome-wide association studies have found single nucleotide polymorphisms in the gene encoding transient receptor potential channel M8. Transient receptor potential channel M8 is generally known as a cold receptor but it has been implicated in pain signaling and may play a role in migraine pain. Methods In order to investigate whether transient receptor potential channel M8 may contribute to the pain of migraine, the transient receptor potential channel M8 activator icilin was applied to the dura mater using a rat behavioral model of headache. Cutaneous allodynia was measured for 5 hours using Von Frey filaments. Results: Dural application of icilin produced cutaneous facial and hind paw allodynia that was attenuated by systemic pretreatment with the transient receptor potential channel M8-selective antagonist AMG1161 (10mg/kg p.o.). Further, the anti-migraine agent sumatriptan (0.6mg/kg s.c.) or the non-selective NOS inhibitor L-NAME (20mg/kg i.p.) also attenuated allodynia when given as a pretreatment. Conclusions These data indicate that transient receptor potential channel M8 activation in the meninges produces behaviors in rats that are consistent with migraine and that are sensitive to pharmacological mechanisms known to have efficacy for migraine in humans. The findings suggest that activation of meningeal transient receptor potential channel M8 may contribute to the pain of migraine.
引用
收藏
页码:185 / 193
页数:9
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