Plasma Calcitonin Gene-related Peptide Research Articles

Plasma Calcitonin Gene-Related Peptide: A Potential Biomarker for Diagnosis and Therapeutic Responses in Pediatric Migraine.

Background: Plasma calcitonin gene-related peptide (CGRP) plays a key role in the migraine pathophysiology. This study aimed to investigate its role in predicting diagnosis and outcome of pharmacotherapy in pediatric migraine.Methods: We prospectively recruited 120 subjects, who never took migraine-preventive agents in a pediatric clinic, including 68 patients with migraine, 30 with non-migraine headache (NM), and 22 non-headache (NH) age-matched controls. Short-term therapeutic response was measured for at least 2 weeks after the start of therapy. Responders were defined with >50% headache reduction. Plasma CGRP concentrations were measured by ELISA.Results: In the migraine group, more patients required acute therapy, as compared to the NM group (62/68, 91% vs. 5/30, 15%, p = 0.001). The mean plasma CGRP level in migraineurs either during (291 ± 60 pg/ml) or between (240 ± 48) attacks was higher than in NM patients (51 ± 5 pg/ml, p = 0.006 and 0.018, respectively) and NH controls (53 ± 6 pg/ml, p = 0.016 and 0.045, respectively). Forty-seven patients (69%) needed preventive treatments and had higher plasma CGRP levels (364 ± 62 pg/ml, n = 47) than those not (183 ± 54 pg/ml, n = 21) (p = 0.031). Topiramate responders had higher plasma CGRP levels than non-responders (437 ± 131 pg/ml, n = 14 vs. 67 ± 19 pg/ml, n = 6, p = 0.021). Survival curves of plasma CGRP levels also showed those with higher CGRP levels responded better to topiramate. Differences were not found in the other preventives.Conclusion: The plasma CGRP level can differentiate migraine from non-migraine headache. It may also serve as a reference for the therapeutic strategy since it is higher in patients requiring migraine prevention and responsive to short-term topiramate treatment. These results are clinically significant, especially for the young children who cannot clearly describe their headache symptoms and may provide new insights into the clinical practice for the diagnosis and treatment of pediatric migraine.

Calcitonin Gene-Related Peptide and Substance P As Predictors of Venous Pelvic Pain.

The purpose of this work was to study the contents of calcitonin gene-related peptide (CGRP) and substance P (SP) in the blood plasma of patients with pelvic varicose veins. Thirty women with pelvic varicosities and a reflux blood flow were investigated using duplex ultrasonography. Group 1 included 18 patients with clinical signs of the pelvic congestion syndrome (PCS), including venous pelvic pain (VPP). Group 2 consisted of 12 patients with pelvic varicosities with no clinical signs of PCS. Group 1. The score of VPP intensity ranged from 4 to 8; the mean score being 4.84 ± 0.43. The CGRP level in the studied group ranged from 0.39 to 1.01 ng/mL; the SP level ranged from 0.005 to 1.33 ng/mL. Group 2. The CGRP values were 0.15–0.32 ng/mL, and the SP range was 0.003–0.3 ng/mL. In this group, the levels of the studied peptides were 3–5 times lower than those for the patients with VPP. Group 3. The mean CGRP values were 0.06 ± 0.003 ng/mL, and the mean SP values were 0.03 ± 0.001 ng/mL. These values were considered as the reference parameters; a statistical analysis was performed for them. The correlation analysis revealed a strong relationship between the CGRP and VPP levels (r = 0.82) and a medium correlation between the SP level and pelvic pain in Group 1. The CGRP and SP levels in blood plasma highly correlate with the presence of pelvic venous pain.

Short Communication: Decreased Plasma Calcitonin Gene-Related Peptide as a Novel Biomarker for HIV-1 Disease Progression

HIV-1 mucosal transmission in genital epithelia occurs through infection of Langerhans cells and subsequent transinfection of CD4+ T cells. We previously reported that the vasodilator neuropeptide calcitonin gene-related peptide (CGRP), secreted upon activation of sensory peripheral neurons that innervate all mucosal epithelia, significantly inhibits transinfection. To investigate the association between CGRP and HIV-1 during infection, we evaluated circulating CGRP levels in HIV-1-infected patients. Plasma was obtained from combination antiretroviral therapy (cART)-naive or cART-treated patients with primary/acute (PHI) or chronic (CHI) HIV-1 infection, as well as from individuals who naturally control HIV-1 infection, namely exposed seronegatives (ESNs), elite controllers (ECs), and long-term nonprogressors (LTNPs). CGRP plasma levels were measured using an enzyme immunoassay. Compared with healthy HIV-1-negative controls, CGRP plasma levels significantly decreased in PHI patients and even further in CHI patients, but remained unchanged in ESNs, ECs, and LTNPs. Moreover, CGRP plasma levels were restored to baseline upon cART in both PHI and CHI. Finally, CGRP plasma levels directly correlated with CD4+ T cell counts and inversely with viral loads. Altogether, CGRP could serve as a novel diagnostic plasma biomarker for progression of HIV-1 infection. Moreover, administration of CGRP to cART-naive HIV-1-infected patients, to compensate for CGRP decline, could help controlling on-going HIV-1 infection.

Study of calcitonin gene-related peptide level in peripheral blood of episodic and chronic migraine patients

Objective The aim of this study was to determine the level of calcitonin gene-related peptide (CGRP) in peripheral blood of patients with episodic migraine (EM) and chronic migraine (CM) compared with the control group. Background Migraine is a common disabling multifactorial recurrent hereditary neurovascular headache disorder. It is burden to the person, the society, and affects one's quality of life. It occurs in childhood and puberty. CGRP increased from trigeminal nerves and play an important role in the painful phase of migraine. Patients and methods A cross-sectional study was conducted on 40 participants suffering from CM and EM and 20 healthy participants as a control group. Venous blood was taken and plasma separated to be stored at −70°C. CGRP was determined by enzyme-linked immunosorbent assay kit. All participates were subjected to full detailed general medical, neurological, and psychiatric history and examination. Results Insignificant difference was recorded among migrainous patients and the control group regarding age, sex, distribution of computed tomography/MRI, fundus examination, and electroencephalogram, whereas migraine patients differ significantly regarding the symptoms such as nausea, vomiting, phonophobia, and photophobia. Moreover, no significant difference was found between men and women in their CGRP levels. Conclusion The level of CGRP plasma was clearly higher in peripheral blood in large series of CM and a lower degree for EM women versus control group in migraine attack.

Detection and significance of calcitonin gene-related peptide in children with enterovirus 71 infected hand foot and mouth disease

Objective To detect the plasma calcitonin gene-related peptide (CGRP) in children with enterovirus 71(EV71) infected hand foot and mouth disease(HFMD), and explore the relationship between CGRP and the severity of EV71 infected HFMD. Methods Two hundred children with EV71 infected HFMD in Xi′an Children′s Hospital from January 2017 to December 2017 were selected as the research group, and 50 healthy children were selected as control group in the same period.According to the severity of the disease, the research group was divided into the mild group (n=142) and the severe group (n=58). The level of plasma CGRP was detected by ELISA. Results In acute stage, the level of CGRP in children with EV71 infected HFMD was lower than that in control group, and the difference was statistically significant (t=4.235, P<0.001). The level of CGRP in acute stage in severe group[(29.90±5.10)pg/ml] was significantly lower than that of the mild group[(35.51±5.48)pg/ml], and the difference was statistically significant (t=6.615, P=0.001). The level of CGRP in mild group[(35.51±5.48)pg/ml] was slightly lower than that of the control group[(36.63±5.65)pg/ml], but the difference was insignificant (t=1.120, P=0.086). In recovery stage, the level of CGRP in the severe group was obviously higher than that in the acute stage(t=5.924, P=0.003). According to the ROC curve of CGRP in mild and severe EV71 infected HFMD, the critical value of CGRP in mild and severe HFMD was 28.12 pg/ml, and the sensitivity was 80.0% and the specificity was 50.0%. Conclusion The CGRP is associated with the progression of EV71 HFMD, and when CGRP is lower than 28.12 pg/ml, suggesting the possibility of severe HFMD.The decrease of plasma CGRP may be a risk factor for the progression of EV71 infected HFMD. Key words: Hand foot and mouth disease; Enterovirus 71; Calcitonin gene-related peptide

Is calcitonin gene-related peptide a modulator of menopausal vasomotor symptoms?

Calcitonin gene-related peptide (CGRP) is a neuropeptide widely distributed in the central and peripheral nervous systems, which is known as a potent vasodilator. Postmenopausal women who experience hot flushes have high levels of plasma CGRP, suggesting its involvement in menopausal vasomotor symptoms. In this review, we describe the biochemical aspects of CGRP and its effects associated with deficiencies of sexual hormones on skin temperature, vasodilatation, and sweating as well as the possible peripheral and central mechanisms involved in these events. Several studies have shown that the effects of CGRP on increasing skin temperature and inducing vasodilatation are potentiated by a deficiency of sex hormones, a common condition of postmenopausal women. Additionally, the medial preoptic area of the hypothalamus, involved in thermoregulation, contains over 25-fold more CGRP-immunoreactive cells in female rodents compared with male rodents, reinforcing the role of female sex hormones on the action of CGRP. Some studies suggest that ovarian hormone deficiency decreases circulating endogenous CGRP, inducing an upregulation of CGRP receptors. Consequently, the high CGRP receptor density, especially in blood vessels, amplifies the stimulatory effects of this neuropeptide to raise skin temperature in postmenopausal women during hot flushes. The duration of the perception of each hot flush in a woman is brief, while local reddening after intradermal administration of α-CGRP persists for 1 to 6 h. This contrast remains unclear.

New therapies to relieve pain: The search for more efficient and safer alternatives to opioid pain killers.

EMBO Reports (2018) e46925 Opioids are a largely efficient medication for relieving severe pain and are prescribed for a wide variety of indications including metastatic cancer, arthritis, neuropathy or post‐surgical pain. These drugs target opioid receptors to produce effects similar to morphine and include moderately strong painkillers such as oxycodone and hydrocodone (Vicodin), and strong drugs like fentanyl, which resembles opium‐derived morphine and heroin. The great efficiency of opioids in treating severe pain has also been the major drawback for longer‐term use given their addictive power. This does not matter for short‐term use, for instance to ease post‐operative pain, or terminal cancer when the primary requirement is to relieve suffering. Yet, the addictive side effect has become a huge societal problem; in addition, opioids do not work against all types of chronic pain, including some of the most severe cases such as cancer‐induced bone pain or some cases of neuropathy resulting from nerve damage. These problems have spurred efforts to develop new drugs for treating pain with some success in developing derivatives with reduced side effects. The other major avenue of research is the identification of relevant pain pathways or protein binding sites including those involved in the placebo effect. Their efficiency has spurred physicians to prescribe opioids too readily, while drug companies have heavily advertised their effects and understated the side effects to boost usage. This three‐way collusion between patients, doctors and pharmaceutical companies has stoked the ongoing epidemic of opioid addiction that has afflicted the USA and Canada in particular, but also other developed countries in Europe and Asia. Apart from exacting a heavy social toll through loss of motivation or loss of jobs, impact on relationships, crime and so on, opioid addiction has dangerous physiological effects, notably on the respiratory system, which causes most of the overdose …

Rutaecarpine protects against bleomycin-induced pulmonary fibrosis through inhibiting Notch1/eIF3a signaling pathway in rats

To investigate whether the protection of rutaecarpine against bleomycin-induced pulmonary fibrosis is mediated by inhibiting Notch1/eukaryotic initiation factor 3a (eIF3a) signaling pathway, and whether these effects are related to the synthesis and release of calcitonin gene-related peptide (CGRP) and inhibition of epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, male Sprague-Dawley rats were randomly divided into five groups (n=12), respectively, Control group, bleomycin group, rutaecarpine (100, 300 mg·kg⁻¹) group and capsaicin plus rutaecarpine (300 mg·kg⁻¹) group. Bleomycin (5 mg·kg⁻¹) was used to induce pulmonary fibrosis rat model. Rats were given capsaicin (50 mg·kg⁻¹) by subcutaneous injections 1 days before and 7, 14, 21 days after induce pulmonary fibrosis rat model to deplete endogenous CGRP. At the end of experiments, blood was collected from carotid artery to determinate the plasma levels of CGRP by ELISA. Pulmonary tissue change was observed by HE staining. Masson's trichrome stain was used to demonstration collagen deposition. The collagen I expression in pulmonary tissue was measured by immunohistochemisty. The expression of CGRP, Notch1, eIF3a, collagen I, vimentin, alpha-smooth muscle actin (α-SMA), E-cadherin and zonula occludens-1 (ZO-1) was detected by qPCR or Western blot. Compared with the control group, the pulmonary tissue of the bleomycin group showed significant fibrosis, including significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, and concomitantly with the decrease in plasma CGRP and expression of CGRP. Importantly the expression of E-cadherin and ZO-1 was decreased and expression of Notch1, eIF3a, collagen I, vimentin and α-SMA was increased in bleomycin group (P<0.05 or P<0.01). Compared with the bleomycin group, rutaecarpine (100, 300 mg·kg⁻¹) group significantly reduced bleomycin-induced pulmonary injury concomitantly with the increase in plasma CGRP and expression of CGRP. Importantly the expression of E-cadherin and ZO-1 was increased and expression of Notch1, eIF3a, collagen I, vimentin and α-SMA was decreased by rutaecarpine treatment (P<0.05 or P<0.01). All these effects of rutaecarpine were abolished by capsaicin.These results suggest that rutaecarpine protects against bleomycin-induced pulmonary fibrosis by inhibiting Notch1/eIF3a signaling pathway, alleviating EMT process, which is related to the increased synthesis and release of CGRP.

Effects of obesity on the healing of bone fracture in mice

BackgroundObesity affects bone health to varying degrees, depending on the skeletal site (weight-bearing or non-weight-bearing) and compartment (cortical or trabecular), and is a risk factor for orthopedic disorders, including bone fractures. However, the effect and mechanisms of obesity on healing of bone fracture is little understood.MethodsThe healing bone fractures of the tibia in genetically obese mice was evaluated relative to normal mice at weekly intervals for 28 days using X-ray scans, hematoxylin and eosin (H&E) stain, and alcian blue (AB) stain. Plasma concentrations of relevant proteins were also compared via enzyme-linked immunosorbent assay (ELISA). These included calcitonin gene-related peptide (CGRP), fibroblast growth factor (FGF), transforming growth factor beta 1 (TGF-β1), and tumor necrosis factor-α (TNF-α).ResultsBone fracture healing was delayed in the obese mice compared with the control group of normal mice, based on X-ray, H&E stain, and AB stain analysis. This was accompanied with significantly low plasma CGRP, FGF, and TGF-β1 (ELISA). However, TNF-α was significantly higher in obese mice compared with the control.ConclusionBone fracture healing was significantly slower in the obese mice, relative to that of normal mice. The lower levels of CGRP, FGF, and TGF-β, and higher level of TNF-α, observed in obese mice may contribute to this observed delay in fracture healing.

A Metabolism-Based Synergy for Total Coumarin Extract of Radix Angelicae Dahuricae and Ligustrazine on Migraine Treatment in Rats

Radix Angelicae dahuricae, containing coumarins, which might affect cytochrome P450 enzyme (CYP450) activity, has been co-administered with ligustrazine, a substrate of CYP450s, for the clinical treatment of migraine. However, whether a pharmacokinetic-based synergy exists between Radix Angelicae dahuricae and ligustrazine is still unknown. In this study, the total coumarin extract (TCE) of Radix Angelicae dahuricae (50 mg/kg, orally) reinforced the anti-migraine activity of ligustrazine by declining head scratching, plasma calcitonin gene-related peptide, and serum nitric oxide, as well as increasing plasma endothelin levels in rats (p < 0.05). Moreover, the pharmacokinetic study reflected that TCE potentiated the area under the concentration–time curve of ligustrazine and prolonged its mean retention time in rats (p < 0.05). Besides, the IC50 for TCE, imperatorin and isoimperatorin inhibiting ligustrazine metabolism were 5.0 ± 1.02, 1.35 ± 0.46, 4.81 ± 1.14 µg/mL in human liver microsomes, and 13.69 ± 1.11, 1.19 ± 1.09, 1.69 ± 1.17 µg/mL in rat liver microsomes, respectively. Moreover, imperatorin and isoimperatorin were CYP450s inhibitors with IC50 < 10 µM for CYP1A2, 2C9, 2D6, and 3A4. Therefore, this study concluded that Radix Angelicae dahuricae could increase ligustrazine plasma concentration and then reinforce its pharmacological effect by inhibiting its metabolism through interference with CYP450s. This could be one mechanism for the synergy between Radix Angelicae dahuricae and ligustrazine on migraine treatment.

Effects of hyperbaric oxygen on vascular endothelial function in patients with slow coronary flow

To improve therapy for slow coronary flow (SCF), the effects of hyperbaric oxygen (HBO) therapy on vascular endothelial function in SCF patients is the focus of this investigation. Ninety-eight patients who exhibited chest discomfort were retrospectively analyzed, and di-agnosed with SCF by coronary artery angiography at the Third Hospital of Hebei Medical University, Shijiazhuang, China from 2014 to 2016. The patients were divided into two groups according to the following treatment: HBO group (n = 48) and the control group (n = 50). Patients in the control group were administrated with conventional treatment, while those in the HBO group were administrated HBO therapy for 4 weeks in addition to conventional treatment. To evaluate the effects of HBO on vas-cular endothelial functions, plasma levels of nitric oxide (NO), calcitonin gene-related peptide (CGRP), endothelin-1 (ET-1), high sensitivity C-reactive protein (hsCRP) as well as endothelial-dependent flow-mediated vasodilation (FMD) of the brachial artery were measured in both groups before and after their respective treatments. There were no significant differences in plasma levels of NO, ET-1, CGRP, hsCRP nor in FMD measurements between the two groups before treatment (p > 0.05). Moreover, the levels of all the parameters measured showed no significant changes before and after treatment in the control group. However, when comparing the control group, FMD and plasma NO and CGRP levels were significantly increased in the HBO group after treatment (p < 0.01), whereas hsCRP and ET-1 levels decreased dramatically (p < 0.001). The HBO treatment in addition to conventional therapy may significantly improve the vascular endothelial function in SCF patients. (Cardiol J 2018; 25, 1: 106-112).

Effect of Electroacupuncture on Expression of 5-HT7 Receptor in Periaqueductal Gray and Plasma Calcitonin Gene-related Peptide in Migraine Rats

To explore the analgesic effect of electroacupuncture(EA)by modulating 5-hydroxytryptamine 7 (5-HT7) receptor in periaqueductal gray (PAG) and plasma calcitonin gene-related peptide (CGRP). Forty-two male Sprague Dawley (SD) rats were randomly divided into control，model and EA groups, 14 rat in each one. The neurogenic migraine model was established by repeated electrical stimulation on sagittal sinus duramater. Intracranial electrodes were used in the control group without stimuli. The rats in the EA group received EA (0.5－1 mA, 2 Hz/15 Hz) at "Fengchi" (GB 20) for 10 min after dural electrical stimulation, once a day for 6 days. The expression of 5-HT7 receptor in the PAG was assessed by immunofluorescence and Western blot, respectively; plasma CGRP was measured by radioimmunoassay. Compared with the control group, the positive neuron number and protein expression of 5-HT7 receptor in PAG and plasma CGRP increased after model establishment (all P<0.001). The above mentioned indexes were reversed in the EA group compared with those in the model group (the positive neuron number and protein expression of 5-HT7 receptor, P<0.01; plasma CGRP, P<0.05). EA at GB 20 can down-regulate the expression of 5-HT7 receptor in the PAG and reduce the content of plasma CGRP in the rats of migraine.

Ghrelin attenuated hyperalgesia induced by chronic nitroglycerin: CGRP and TRPV1 as targets for migraine management.

Background According to the neurovascular theory of migraine, activation of the trigeminovascular system contributes to the development of migraine. This study examined the effects of chronic intraperitoneal ghrelin (150 µg/kg) treatment on the development of chronic migraine induced by intermittent injection of nitroglycerin 10 mg/kg. Methods Baseline and post-drug (2 h following nitroglycerin injection) mechanical and thermal sensitivity were assessed by von Frey hair and tail immersion tests, respectively on days 1, 3, 5, 7, 9 and 11. Moreover, we investigated the effect of ghrelin treatment on nitroglycerin-induced aversive behavior by using a two-chamber conditioned place aversion paradigm. At the end of behavioral testing, on day 11, animals were sacrificed and plasma concentration of calcitonin gene-related peptide was measured using a rat-specific enzyme-linked immunosorbent assay kit. Also, real time polymerase chain reaction was used to quantify mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid 1 in the trigeminal ganglion. Results Our results indicated that nitroglycerin activated the trigeminovascular system, which was reflected by mechanical and thermal hypersensitivity and elevation of mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid-1, as migraine markers, and plasma calcitonin gene-related peptide levels. Moreover, chronic nitroglycerin injection induced conditioned place aversion and body weight loss. Nevertheless, ghrelin modulated nitroglycerin-triggered changes in transient receptor potential vanilloid-1 and calcitonin gene-related peptide expression, and mitigated nitroglycerin-induced hyperalgesia. Conclusion These results provide the first convincing evidence that ghrelin has a modulating effect on central sensitization induced by chronic intermittent nitroglycerin, and its antinociceptive effect may be related to a reduction of these factors in the trigeminal ganglion.

Calcitonin gene-related peptide antagonism and cluster headache: an emerging new treatment.

Calcitonin gene-related peptide (CGRP) is a key signaling molecule involved in migraine pathophysiology. Efficacy of CGRP monoclonal antibodies and antagonists in migraine treatment has fueled an increasing interest in the prospect of treating cluster headache (CH) with CGRP antagonism. The exact role of CGRP and its mechanism of action in CH have not been fully clarified. A search for original studies and randomized controlled trials (RCTs) published in English was performed in PubMed and in ClinicalTrials.gov . The search term used was "cluster headache and calcitonin gene related peptide" and "primary headaches and calcitonin gene related peptide." Reference lists of identified articles were also searched for additional relevant papers. Human experimental studies have reported elevated plasma CGRP levels during both spontaneous and glyceryl trinitrate-induced cluster attacks. CGRP may play an important role in cluster headache pathophysiology. More refined human studies are warranted with regard to assay validation and using larger sample sizes. The results from RCTs may reveal the therapeutic potential of CGRP monoclonal antibodies and antagonists for cluster headache treatment.

Chemical Composition and Antimigraine Activity of Essential Oil of Angelicae dahuricae Radix.

The aim of this study was to explore the chemical composition and the effect of essential oil of Angelicae dahuricae radix on a nitroglycerin (NTG)-induced rat model of migraine. The CO2 supercritical fluid extraction method was optimized for the extraction of essential oil of A. dahuricae radix (EOAD) and its chemical composition was determined. The migraine model was established by subcutaneous injection of NTG (10 mg/kg) 1 h after the last administration of EOAD. The therapeutic effect of EOAD and its underlying mechanism were assessed by monitoring behavioral changes, levels of nitric oxide (NO) in serum and brain tissues, plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET), and ET/NO ratio. The optimal conditions for CO2 supercritical fluid extraction of EOAD, as determined by orthogonal test [L9(34)], were as follows: 2 h extraction time, 20 MPa pressure, 40°C temperature, and 30 mesh. The yield of EOAD was 1.8%. On gas chromatography-mass spectrometry, 45 peaks were found in EOAD, and 22 compounds were identified and quantified. The main constituents of EOAD were 1-dodecanol (13.71%), elemene (7.54%), palmitic acid ethyl ester (7.32%), α-pinene (6.25%), and 1-pentadecanol (6.08%). Compared with rat migraine model controls, EOAD (35, 70, and 140 mg/kg) significantly reduced the number of head shaking, head scratching, and hind leg shooting events, decreased serum and brain NO levels, decreased plasma CGRP, and increased ET levels in rats. ET/NO ratio was elevated to 28.68 in the EOAD high-dose group. EOAD ameliorates NTG-induced migraine in rats likely by modulating the levels of vasoactive substances.

Venopunction of the cubital vein as an alternative approach for CGRP plasma level evaluation in tmd patients

Calcitonin gene-related peptide is an important vasodilator. It plays an important role in the metabolism of chewing muscles. The aim of the study was to evaluate the plasma level of CGRP in patients with myofascial pain (RDC/TMD Ia) and myofascial pain with limited opening (RDC/TMD Ib) before and after occlusal splint therapy (Michigan splint). A randomised trial was performed including 39 patients (males = 3, females = 36). Blood samples were taken from the external jugular vein (JUG) and cubital vein (CUB) before and after 30 days of occlusal splint therapy. Plasma levels of CGRP were measured with ELISA KIT for Human Calcitonin Gene Related Peptide (CGRP) 96T (USCNK Business Co. Ltd.). The results of the study show that the plasma CGRP level was higher in the external jugular vein (JUG1 = 5.07pg/mL [SD = 1.99]) than in cubital vein (CUB1 = 4.3 pg/mL [SD = 1.6]). After 30 days of the occlusal splint therapy the levels in both veins increased: JUG2 = 6.07 pg/mL (SD = 2.19), and CUB2 = 4.9 pg/mL (SD = 1.4). The CGRP plasma level increase was statistically significant only in the external jugular vein (JUG) (p < 0.05). Statistically significant pain intensity reduction was observed: VAS1 = 5.4 (SD = 2.08) decreased to VAS2 = 1.7 (SD = 2.07) after splint therapy (p < 0.05). Venepuncture of an external jugular vein is more precise, than venepuncture of a cubital vein in evaluating CGRP plasma level changes in patients with TMD.

Circadian Alteration of Plasma Calcitonin Gene-Related Peptide, Endothelin-1 and Hemodynamic Parameters In Normotensive and Hypertensive Rats

Circadian Alteration of Plasma Calcitonin Gene-Related Peptide, Endothelin-1 and Hemodynamic Parameters In Normotensive and Hypertensive Rats

Calcitonin gene-related peptide in peripheral blood as a biomarker for migraine

There is no available biomarker for any of the primary headaches, including migraine. As demonstrated in jugular blood, during a migraine attack, trigeminal activation releases several neuropeptides, very especially calcitonin gene-related peptide (CGRP), which gives rise to the typical throbbing migraine pain. Here, we review the current evidence for measurement of peripheral CGRP levels as a potential biomarker for trigemino-vascular activation in migraine. Several studies, including a limited number of migraine patients, have shown increased peripheral CGRP levels during migraine attacks. The maximum increase in plasma CGRP levels was reached within 2 h of the onset of the attacks and can be reverted by triptans. In addition, CGRP levels measured in peripheral blood outside migraine attacks and in the absence of symptomatic medication have been shown to be increased in chronic migraine patients. Increased CGRP levels were able to predict the response to onabotulinumtoxinA treatment and were reduced 1 month after onabotulinumtypeA therapy. Although CGRP data must be confirmed and expanded in future studies and specificity of CGRP levels should be studied in entities able to resemble migraine, it seems that peripheral CGRP levels are a good biomarker of acute migraine and somewhat specific and sensitive interictally in chronic migraine.

Calcitonin Gene-Related Peptide as a Biomarker in Migraine

Background: Migraine is a prevalent disease with much economic burden and relatively inadequate available treatment. Calcitonin gene-related peptide (CGRP) is the most abundant neuropeptide in the trigeminal nerve and it may be involved in the pathogenesis of migraine. The aim of the study was to determine the plasma level of CGRP in patients with primary headache, and if it could be a potential biomarker for migraine. Methods: The study involved four groups with 20 patients in each one: chronic migraine, episodic migraine, cluster headache and tension type headache subjects, as well as healthy volunteers of matched age and sex as controls. Their venous blood was drawn, plasma was separated, and CGRP was analyzed with commercially available ELISA kit. Results: Plasma CGRP levels were significantly increased in chronic migraine (165.0 ± 17.9 ng/L, range 131.8 - 194.6) as compared with control group (70.5 ± 8.36 ng/L, range 51.7 - 83.65), patients with episodic migraine (94.1 ± 17.83 ng/L, range 69.6 - 121.9), and patients with cluster headache and tension type headache (87.2 ± 13.8 ng/L, range 62.8 - 110.8). Plasma CGRP levels in chronic migraine were significantly higher in patients with aura (191.32 ± 5.09, range 185.45 - 194.60) than without aura (160.30 ± 14.93, range 131.80 - 186.0), and in episodic migraine were significantly higher in patients with aura (109.88 ± 7.54, range 100.70 - 116.30) than without aura (90.16 ± 17.56, range 69.60 - 121.90). Conclusion: The plasma CGRP levels were elevated in patients with chronic migraine and may be considered a potential biomarker for it. This opens the door for a therapeutic role of it for migraine. J Neurol Res. 2017;7(6):103-107 doi: https://doi.org/10.14740/jnr460w

Effect of three vertigo-stopping needles on neurohumor of patients with cervical vertigo: a controlled trial

ObjectiveTo observe the effect of three vertigo-stopping needles on the contents of neuropeptide Y (NPY), endothelin (ET) and calcitonin gene-related peptide (CGRP) in plasma of patients with cervical vertigo, and to explore its mechanism of treatment. MethodsOne hundred and eighty patients with cervical vertigo were divided into group A [acupuncture at Rényíng (▪ ST 9) and Fēngchí (▪ GB 20), and frontal line], group B [acupuncture at Jing jiāji (▪), GB 20 and Baihuì (▪ GV 20)] and group C [intravenous infusion with ligustrazine and oral administration with flunarizine] according to simple randomization, with 60 cases in each group. For the patients in group A and group B, the treatment was conducted once a day, and ten times were considered as one course of treatment. Two days were free of treatment between two courses, and two courses were needed. For the patients in group C, the treatment was conducted for fifteen days. The contents of NPY, ET and CGRP in plasma before and after treatment were detected in patients with cervical vertigo. ResultsThe contents of NPY in plasma of patients in the three groups after treatment were markedly lower than that before treatment (all P<0.01), and the differences were not statistically significant when compared the descending degrees among three groups (P>0.05). The contents of ET in plasma of patients in the three groups after treatment were markedly lower than that before treatment (P<0.05, P<0.01), the descending degree in group A was greater than that in group B and group C, and the difference was statistically significant (P<0.01, P<0.05); while the difference was not statistically significant when compared the descending degrees between group B and group C (P>0.05). The contents of CGRP in plasma of patients in the three groups after treatment were markedly higher than that before treatment (P<0.05, P<0.01), the increasing degree in group A was greater than that in group B and group C, and the difference was statistically significant (both P<0.05); while the difference was not statistically significant when compared the increasing degrees between group B and group C (P>0.05). ConclusionThree vertigo-stopping needles, acupuncture and medication can regulate the contents of NPY, ET and CGRP in plasma of patients with cervical vertigo, while three vertigo-stopping needles is significantly superior to acupuncture and medication in reducing ET and increasing CGRP.