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Effects of acupuncture on 5-hydroxytryptamine1F and inducible nitricoxide synthase gene expression in the brain of migraine rats
Abstract
Aim: Early experiments have proved that acupuncture has better curative effect in treating migraine. In this study, we explore the regulatory effect of acupuncture on the expression of 5-hydroxytryptamine1F (5-HT1F) and inducible nitricoxide synthase (iNOS) in brain of rats with migraine. Methods: The experiment was conducted at the laboratory of Integrative Traditional and Western Medicine Institute, Xiangya Hospital Affiliated to Central South University from November 2005 to May 2006. 1 Forty SD rats were randomly divided into 4 groups (n =10). The model of migraine was established in all rats except control group. Additionally, acupuncture treatment group was acupunctured at bilateral Taichong and Yanglingquan for 20 minutes (sparse and dense wave, 0.3-0.6 mA, once daily for 5 times) after modeling, and acupuncture prevention group was acupunctured by the same method before modeling. 2 The expression of 5-HT1F and iNOS mRNA was measured by RT-PCR method. Results: Ten rats of normal control group, 9 of other groups were involved in the result analysis, and 3 were lost. 1 Compared with the normal control group, iNOS mRNA expression in the brain of model control group was significantly raised (P < 0.01), but 5-HT1F mRNA expression was significantly reduced (P < 0.01). 2 Compared with the model control group, the iNOS mRNA expression of the acupuncture prevention and treatment group was, remarkably decreased (P < 0.01), but 5-HT1F mRNA expression was markedly increased (P < 0.01). Conclusion: Acupuncture may prevent and cure migraine by controlling and regulating the expression of 5-HT1F and iNOS mRNA.
... Modulating extracranial and intracranial blood flow (33). Affecting serotonin (5-hydroxytriptamine) levels in the brain (34). ...
Acupuncture is a portion of traditional Chinese medicine and has been used for Health care over 3,000 years in China. A migraine is a relatively common medical condition that can severely affect the quality of life of the sufferer and his or her family. Migraine is ranked by the World Health Organization as the 19th disease world-wide to cause disability; epidemiological studies of headache in Asia reported consistent findings that the prevalence ranged from 8.4% to 12.7%. Objective: To assess the efficacy of acupuncture in migraine prophylaxis. Patients and method: This study was carried out on 40 known case of migraineurs from both genders, aged 20-50 years. Migraineurs were randomly divided into 2 groups, 20 cases in each group, first group (control group) received medical treatment i.e. propranolol 40mg tid while 2nd group (acupuncture group) received 15 sessions of real acupuncture for 12 weeks, These forty migraineurs were treated in Emam Reza Hospital in Mashhad city in Iran and in private clinic of Dr. Mojtabavi over a period from December 2011 till March 2012. Statistical analysis was done by using SPSS in which independent t-test was used to compute significance. Result: There were significant differences between the acupuncture and control groups throughout the treatment periods on numbers of attacks and intensity of pain i.e. there is significant decrease, in numbers of migraine attacks and intensity of pain, more in patients treated with acupuncture than those treated with the medical therapy (propranolol). Conclusion: acupuncture is more effective, in reducing the frequency of attacks and intensity of the pain, than medical treatment for migraine prophylaxis.
... e theory of TCM also believes the human body will suffer from illness or disease once this flow is abnormal, which can be recovered by inserting the needle in some specified points on the channels of meridians of the human body like acupuncture. Acupuncture is often used to treat headache including migraine [7], and its therapeutic mechanism may be related to its regulation of nitric oxide synthase and 5-hydroxytryptamine (5-HT) gene 1F expression to improve cerebral vasodilation and contraction [8]. ...
Objectives:
To review the evidence of acupuncture for acute and preventive treatment of migraine for further awareness of the effect of acupuncture for migraine.
Design:
An overview of systematic reviews and meta-analyses (SR/MAs) for randomized controlled trials.
Material and methods:
We searched PubMed, Embase, the Cochrane Library, China Knowledge Resource Integrated Database, VIP Chinese Journal Full Text Database, WANFANG Data, and China Biology Medicine disc from their establishment to May 27, 2018. SR/MAs of randomized controlled trials comparing the effect of the acupuncture intervention with another treatment control in migraine patients were included.
Results:
428 SRs were identified, and 15 of them were included. Only 4 SR/MAs were assessed by GRADE, which showed certainty of most evidence being low or very low. Assessed by AMSTAR-2, fourteen was critically low rating overall confidence in the results, and 1 was low rating overall confidence in the results. Evidence suggested that acupuncture has a significant advantage of pain improvement, efficacy, and safety relative to blank control, sham acupuncture, or drug treatment, but some of these results are contradictory.
Conclusions:
We found that acupuncture on treating migraine has the advantage for pain improvement and safety, but the quality of SR/MAs of acupuncture for migraine remains to be improved.
Acupuncture has historically been in clinical practice in China since a long time and today has spread to many other parts of the world as well. Accumulating evidence shows that manual acupuncture (MA) and electroacupuncture (EA) induce therapeutic effects on multiple disorders that have been demonstrated not only by the Oriental clinicians but also by Western medical community. A large body of literature shows that acupuncture affects the central nervous system (CNS) through regulation of neurotransmitters in terms of their synthesis, release, uptake, and degradation, suggesting an involvement of neurotransmitters in acupuncture therapy. In this chapter, we will update on these vantage points in view of the recent studies on acupuncture effects on neural transmitters/modulators. Besides technical development (e.g., fMRI and PET for measuring endogenous opioid concentrations in the brain), recent evidence suggests that (1) acupuncture can induce dual-directional regulation of endogenous opioids, monoamine substance P, and other transmitters/modulators, depending on acupuncture condition and body status (e.g., normal vs. disease); (2) acupuncture can increase the mRNA expression of brain-derived neurotrophic factor and enhance the expression of neurotrophic factor (NTF) receptors; (3) acupuncture downregulates the nitric oxide (NO) level in the CNS and elevates the NO content in plasma and certain organs; (4) EA can suppress the activation of acetylcholinesterase to attenuate acetylcholine degradation; (5) EA has a better effect on enhancing 5-HT mRNA expression than MA; (6) MA and EA have differential effects on different subtypes of glutamate receptors, leading to decreased expression of N-methyl-d-aspartate (NMDA) receptor and increased expression of AMPA receptor; and (7) EA increases the concentration of prostaglandins in plasma in some diseased states. These studies show that acupuncture induces comprehensive effects on transmitters/modulators in the CNS, and the outcome can be dual-directional depending on acupuncture approach and the body status.
Cortical spreading depression (CSD) is a temporary disruption of local ionic homeostasis that propagates slowly across the cerebral cortex, and may contribute to the pathophysiology of stroke and migraine. Previous studies demonstrated that nitric oxide (NO) formation promotes the repolarisation phase of CSD, and this effect may be cyclic GMP (cGMP)-mediated. Here, we have examined how phosphodiesterase (PDE) inhibition, either alone or superimposed on NO synthase (NOS) inhibition, alters CSD and the associated changes in extracellular cGMP. Microdialysis probes incorporating an electrode were implanted into the frontoparietal cortex of anaesthetised rats for quantitative recording of CSD, pharmacological manipulations, and dialysate sampling for cGMP measurements. CSD was induced by cathodal electrical stimulation in the region under study by microdialysis. Extracellular cGMP increased, but only slightly, during CSD. Perfusion of either zaprinast or sildenafil through the microdialysis probe, at concentrations that inhibited both PDE5 and PDE9 (and possibly other PDE), increased significantly extracellular cGMP. Unexpectedly, these levels remained high when NOS was subsequently inhibited with N(omega)-nitro-l-arginine methyl ester hydrochloride (l-NAME, 1mM). The most interesting pharmacological effect on CSD was obtained with sildenafil. This drug altered neither CSD nor the subsequent characteristic effect of NOS inhibition, i.e. a marked widening of CSD. The fact that NOS inhibition still widened CSD in the presence of the high extracellular levels of cGMP associated with PDE inhibition, suggests that NO may promote CSD recovery, independently of cGMP formation.
Nitric oxide (NO) levels in plasma and urine were determined in 5 girls with ornithine transcarbamylase deficiency (OTCD) of late-onset type, who often developed migraine-like headache or vomiting. The patients were found to have low NO synthesis, suggesting that the low NO synthesis contributes to the clinical manifestations of urea cycle defect.
The aim of the present study was to evaluate the role of nitric oxide (NO) of sensory neural origin in neurogenic inflammatory response in the trigeminovascular system. Antidromic vasodilatation and plasma extravasation in response to electrical stimulation (15 V, 5 Hz, 0.5 ms, 100 impulses) of the trigeminal ganglion were investigated in the dura mater and nasal mucosa/upper eyelid by laser Doppler flowmetry and [(125)I]-labelled bovine serum albumin, respectively. Electrical stimulation of the trigeminal ganglion of rats elicited a reproducible ipsilateral enhancement of both meningeal and nasal mucosal blood flow. N(omega)-nitro-L-arginine (L-NNA; 4, 8, and 16 mg/kg, i.v.), a nonselective inhibitor of nitric oxide synthase (NOS), inhibited antidromic vasodilatation both in the dura mater (15.86+/-2.05%, 22.82+/-2.51%, and 36.28+/-4.37%) and nasal mucosa (35.46+/-8.57%, 58.72+/-9.2%, and 89.99+/-8.94%) in a dose-dependent manner. Specific inhibitors of neuronal NOS, 7-nitroindazole (7-NI; 20 mg/kg, i.v.) and 3-bromo-7-nitroindazole (3Br-7NI; 10 mg/kg, i.v.) were administered to assess the possible role of NO released from the trigeminal sensory fibres. The meningeal vasodilatation was inhibited by both 3Br-7NI and 7-NI (63.36+/-7.7% and 49+/-6.5%, respectively). The nasal hyperaemic response was also reduced by 3Br-7NI (78.26+/-8.7%). Plasma extravasation in the dura mater and upper eyelid evoked by electrical stimulation of the trigeminal ganglion (25 V, 5 Hz, 0,5 ms, 5 min), expressed as extravasation ratios (ERs) of the stimulated vs. nonstimulated sides, was 1.80+/-0.8 and 4.63+/-1.24, respectively. This neurogenic oedema formation was not inhibited by neither L-NNA nor 3Br-7NI. It is concluded that neural nitrergic mechanisms are involved in the meningeal vasodilatation evoked by electrical stimulation of the trigeminal ganglion.
Substituted amphetamines such as p-chloroamphetamine and the abused drug methylenedioxymethamphetamine cause selective destruction of serotonin axons in rats, by unknown mechanisms. Since some serotonin neurones also express neuronal nitric oxide synthase, which has been implicated in neurotoxicity, the present study was undertaken to determine whether nitric oxide synthase expressing serotonin neurones are selectively vulnerable to methylenedioxymethamphetamine or p-chloroamphetamine. Using double-labeling immunocytochemistry and double in situ hybridization for nitric oxide synthase and the serotonin transporter, it was confirmed that about two thirds of serotonergic cell bodies in the dorsal raphé nucleus expressed nitric oxide synthase, however few if any serotonin transporter immunoreactive axons in striatum expressed nitric oxide synthase at detectable levels. Methylenedioxymethamphetamine (30 mg/kg) or p-chloroamphetamine (2 x 10 mg/kg) was administered to Sprague-Dawley rats, and 7 days after drug administration there were modest decreases in the levels of serotonin transporter protein in frontal cortex, and striatum using Western blotting, even though axonal loss could be clearly seen by immunostaining. p-Chloroamphetamine or methylenedioxymethamphetamine administration did not alter the level of nitric oxide synthase in striatum or frontal cortex, determined by Western blotting. Analysis of serotonin neuronal cell bodies 7 days after p-chloroamphetamine treatment, revealed a net down-regulation of serotonin transporter mRNA levels, and a profound change in expression of nitric oxide synthase, with 33% of serotonin transporter mRNA positive cells containing nitric oxide synthase mRNA, compared with 65% in control animals. Altogether these results support the hypothesis that serotonin neurones which express nitric oxide synthase are most vulnerable to substituted amphetamine toxicity, supporting the concept that the selective vulnerability of serotonin neurones has a molecular basis.