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)

Lithium is currently a major drug used as a treatment for affective disorders and cluster headache, among other conditions. Its mechanism of action remains unknown. The trigeminovascular system may be involved in the pathophysiology of cluster headache and related diseases by liberating neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) in the eye-forehead region. The objective of this study was to investigate whether or not a low concentration of lithium may interfere with peptidergic neuro-transmission at this level. Vasoactive intestinal peptide (VIP), SP, CGRP, capsaicin, and SP+CGRP concentration-response relaxation curves were obtained in the presence and absence of 2 x 10(-4) M lithium in isolated porcine ophthalmic arteries. Lithium inhibited the SP and VIP, but not the CGRP responses. Capsaicin-(a neurotoxin causing release of stored sensory neuropeptides) induced relaxations were partially inhibited by lithium. It is concluded that lithium may interfere with SP- and VIP-induced relaxation. If SP and VIP are of pathogenic significance in cluster headache, lithium may possibly work by counteracting unwanted effects of such peptides.
Headache 1992 Jul
PMID:Lithium inhibits substance P and vasoactive intestinal peptide-induced relaxations on isolated porcine ophthalmic artery. 138 46

Nitric oxide (NO) and neurogenic inflammation in dura mater due to nociceptor activation has been implicated for pathophysiology of primary headache disorders. Development of migraine has also been observed in patients treated with ganglion blockage for sympathetic reflex dystrophy. Vasoactive intestinal peptide (VIP) is an antioxidant, anti-inflammatory, and neuroprotective neuropeptide. This study is intended to investigate the effects of VIP on dura mater NO levels and vessel-contraction responses in sympathectomized rats. In the experiments, 30 male rats in five groups were used. Group 1 sympathectomized: under anesthesia, superior cervical sympathetic ganglion was removed via incision at the center line in the neck area. Group 2 sympathectomized + VIP: postoperative VIP of 25 ng/kg/day (0.2 ml) intraperitoneally administered to the rats exposed to the same operations for 5 days. Group 3 sham: ganglia and nerves were exposed but not dissected. Group 4 control: no treatment was done. Group 5 VIP: only VIP was administered for 5 days. Sympathectomy induced a significant increase in dura mater NO levels and VIP decreased NO to control levels and increased the norepinephrine vessel-contraction responses of sympathectomized rats. VIP is an efficient NO modulator in superior cervical ganglionectomized rats.
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PMID:The effects of vasoactive intestinal peptide on dura mater nitric oxide levels and vessel-contraction responses in sympathectomized rats. 1993 38

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) are potent vasodilators in animals and humans. PACAP infusion but not VIP infusion precipitates migraine attacks in migraine patients. The vascular effects of VIP and the two varieties of PACAP (PACAP-27 and PACAP-38) were investigated versus selective antagonists in segments of rat middle cerebral arteries (MCA), basilar arteries (BA) and middle meningeal arteries (MMA) using myographs. The luminal and abluminal effects of VIP were studied using perfusion myograph. mRNA expression of the relevant receptors (VPAC(1), VPAC(2) and PAC(1)) was examined by in situ hybridization. There was no significant difference in relaxant potency of the peptides in the MCA. In BA the relaxant potency was VIP>PACAP-27=PACAP-38. Relaxant responses were either absent or very weak in MMA. VIP was found to be somewhat more potent in BA than in the MCA. Maxadilan, a selective PAC(1)-receptor agonist, showed no relaxant effect in either vessel. The VPAC(2)-antagonist PG 99-465 alone proved ineffective in the MCA, while it had a weak effect on BA. The VPAC(1)-antagonist PG 97-269 inhibited relaxation induced by both VIP and the PACAPs in cerebral vessels. In combination, the two antagonists demonstrated better effect than either alone. VIP applied luminally via perfusion myograph caused no dilatation, indicating lack of endothelial involvement. In situ hybridization demonstrated the presence of mRNA for all three receptors in the smooth muscle cells of the vessels. In conclusion, migraine-like headache induced by PACAP-38 infusion is unlikely to be caused by direct vasodilator action on intracranial vessels.
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PMID:Pharmacological characterization and expression of VIP and PACAP receptors in isolated cranial arteries of the rat. 2191 46

Chronic use of opioids can produce opioid-induced hyperalgesia (OIH), and when used to treat migraine, these drugs can result in increased pain and headache chronicity. We hypothesized that overlapping mechanisms between OIH and chronic migraine occur through neuropeptide dysregulation. Using label-free, non-biased liquid chromatography-mass spectrometry to identify and measure changes in more than 1500 neuropeptides under these two conditions, we observed only 16 neuropeptides that were altered between the two conditions. The known pro-migraine molecule, calcitonin-gene related peptide, was among seven peptides associated with chronic migraine, with several pain-processing neuropeptides among the nine other peptides affected in OIH. Further, composite peptide complements Pituitary adenylate cyclase-activating polypeptide (PACAP), Vasoactive intestinal peptide (VIP) and Secretogranin (SCG) showed significant changes in both chronic migraine and OIH. In a follow-up pharmacological study, we confirmed the role of PACAP in models of these two disorders, validating the effectiveness of our peptidomic approach, and identifying PACAP as a mechanistic link between chronic migraine and OIH. Data are available via ProteomeXchange with identifier PXD013362.
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PMID:PACAP and Other Neuropeptide Targets Link Chronic Migraine and Opioid-induced Hyperalgesia in Mouse Models. 3164 62