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

Nitroglycerin (NTG) in situ reduces the pressure of the upper anal sphincter (UAS). We have tested the effects of NTG on the UAS of patients with terminal constipation. We studied two groups of constipated patients. Group 1 consisted of 11 patients (nine females and two males) with hypertonicity of the UAS (> 70 mm Hg); age was 49.5 +/- 15.6 years. Group 2 consisted of 10 patients (nine females and one male) without hypertonicity; age was 40.1 +/- 14.1 years. Group 3 consisted of eight asymptomatic controls (four females and four males); age was 51.7 +/- 6.9 years. After a 10-minute resting pressure recording of the UAS with a water-filled balloon, the probe was pulled through the outside and the UAS was assessed after spreading 5 mg of placebo and then 5 mg of NTG on the balloon. Resting pressure (RP), delay of the pressure decrease (DP), pressure after five minutes either during the NTG (PN5) or placebo (PP5) period, and mean duration of the pressure decrease (MD) were measured. None of the subjects experienced a decrease of PP5 vs. RP. All patients in Group 1 (106.2 vs. 38.4 mm Hg), Group 2 (57.9 vs. 31.4 mm Hg), and controls (62.2 vs. 33.7 mm Hg) experienced a significant decrease of pressure of the UAS (P < 0.005). Delay of the pressure decrease was less than two minutes, with wide interindividual variability of duration of the pressure decrease. Mild side effects--anal pain and transient headache--were reported in five patients. In situ NTG significantly reduced UAS Pressure in all groups. NTG has to be evaluated in anal pathology, especially in patients with hypertonic sphincter terminal constipation or acute hypertonicity of the sphincter due to a fissure.
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PMID:Action of in situ nitroglycerin on upper anal canal pressure of patients with terminal constipation. A pilot study. 845 65

Medication-overuse headaches (MOH) occur with both over-the-counter and pain-relief medicines, including paracetamol, opioids and combination analgesics. The mechanisms that lead to MOH are still uncertain. Here, we show that abnormal activation of Nav1.9 channels by Nitric Oxide (NO) is responsible for MOH induced by triptan migraine medicine. Deletion of the Scn11a gene in MOH mice abrogates NO-mediated symptoms, including cephalic and extracephalic allodynia, photophobia and phonophobia. NO strongly activates Nav1.9 in dural afferent neurons from MOH but not normal mice. Abnormal activation of Nav1.9 triggers CGRP secretion, causing artery dilatation and degranulation of mast cells. In turn, released mast cell mediators potentiates Nav1.9 in meningeal nociceptors, exacerbating inflammation and pain signal. Analysis of signaling networks indicates that PKA is downregulated in trigeminal neurons from MOH mice, relieving its inhibitory action on NO-Nav1.9 coupling. Thus, anomalous activation of Nav1.9 channels by NO, as a result of chronic medication, promotes MOH.
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PMID:Maladaptive activation of Nav1.9 channels by nitric oxide causes triptan-induced medication overuse headache. 3153 33