Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In animal models endogenous cannabinoids have an inhibitory effect on trigeminovascular activation through the cannabinoid receptor 1 (CB1), although there is no evidence of the potential role of CB1 in human migraine. In this study we applied single marker association and haplotypic trend regression analysis to investigate the relationship between the CB1 gene (CNR1) and headache with migraine symptoms (nausea, photophobia and disability, measured by the ID-migraine questionnaire). We identified our controls (CO=684) as those who have not reported ID-migraine symptoms at all and defined migraine headache sufferers (M=195) as those who reported all three symptoms. The CNR1 was covered by 10 SNPs located throughout the gene based on haplotype tagging (htSNP) and previous literature. Our results demonstrated a significant haplotypic effect of CNR1 on migraine headaches (p=0.008, after permutation p=0.017). This effect was independent of reported depression or drug/alcohol abuse although using neuroticism in the analysis as covariant slightly decreased this association (p=0.027, permutated p=0.052). These results suggest a significant effect of CNR1 on migraine headaches that might be related to the alteration of peripheral trigeminovascular activation. In addition, this is the first study to demonstrate the effectiveness of using trait components combinations to define extreme phenotypes with haplotype analysis in genetic association studies for migraine. However, further studies are needed to elucidate the role of CNR1 and the cannabinoid system in migraine.
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PMID:Variations in the cannabinoid receptor 1 gene predispose to migraine. 1953

The peripheral trigeminovascular pathway mediates orofacial and craniofacial pain and projects centrally to the brainstem trigeminal nucleus caudalis (TNc). Sensitization of this pathway is involved in many pain conditions, but little is known about synaptic plasticity at its first central synapse. We have taken advantage of optogenetics to investigate plasticity selectively evoked at synapses of nociceptive primary afferents onto TNc neurons. Based on immunolabeling in the trigeminal ganglia, TRPV1-lineage neurons comprise primarily peptidergic and nonpeptidergic nociceptors. Optical stimulation of channelrhodopsin-expressing axons in the TRPV1/ChR2 mouse in TNc slices thus allowed us to activate a nociceptor-enriched subset of primary afferents. We recorded from lamina I/II neurons in acutely prepared transverse TNc slices, and alternately stimulated two independent afferent pathways, one with light-activated nociceptive afferents and the other with electrically-activated inputs. Low-frequency optical stimulation induced robust long-term depression (LTD) of optically-evoked EPSCs, but not of electrically-evoked EPSCs in the same neurons. Blocking NMDA receptors or nitric oxide synthase strongly attenuated LTD, whereas a cannabinoid receptor 1 antagonist had no effect. The neuropeptide PACAP-38 or the nitric oxide donors nitroglycerin or sodium nitroprusside are pharmacologic triggers of human headache. Bath application of any of these three compounds also persistently depressed optically-evoked EPSCs. Together, our data show that LTD of nociceptive afferent synapses on trigeminal nucleus neurons is elicited when the afferents are activated at frequencies consistent with the development of central sensitization of the trigeminovascular pathway.SIGNIFICANCE STATEMENT Animal models suggest that sensitization of trigeminovascular afferents plays a major role in craniofacial pain syndromes including primary headaches and trigeminal neuralgia, yet little is known about synaptic transmission and plasticity in the brainstem trigeminal nucleus caudalis (TNc). Here we used optogenetics to selectively drive a nociceptor-enriched population of trigeminal afferents while recording from superficial laminae neurons in the TNc. Low-frequency optical stimulation evoked robust long-term depression at TRPV1/ChR2 synapses. Moreover, application of three different headache trigger drugs also depressed TRPV1/ChR2 synapses. Synaptic depression at these primary afferent synapses may represent a newly identified mechanism contributing to central sensitization during headache.
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PMID:Long-Term Depression Induced by Optogenetically Driven Nociceptive Inputs to Trigeminal Nucleus Caudalis or Headache Triggers. 3005 91