Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine.

Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNFalpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine.

Evaluation of ADMA-DDAH-NOS axis in specific brain areas following nitroglycerin administration: study in an animal model of migraine.

BACKGROUND: Nitric oxide (NO) is known to play a key role in migraine pathogenesis, but modulation of NO synthesis has failed so far to show efficacy in migraine treatment. Asymmetric dimethylarginine (ADMA) is a NO synthase (NOS) inhibitor, whose levels are regulated by dimethylarginine dimethylaminohydrolase (DDAH). Systemic administration of nitroglycerin (or glyceryl trinitrate, GTN) is a NO donor that consistently induces spontaneous-like headache attacks in migraneurs. GTN administration induces an increase in neuronal NOS (nNOS) that is simultaneous with a hyperalgesic condition. GTN administration has been used for years as an experimental animal model of migraine. In order to gain further insights in the precise mechanisms involved in the relationships between NO synthesis and migraine, we analyzed changes induced by GTN administration in ADMA levels, DDHA-1 mRNA expression and the expression of neuronal and endothelial NOS (nNOS and eNOS) in the brain. We also evaluated ADMA levels in the serum. METHODS: Male Sprague-Dawley rats were injected with GTN (10 mg/kg, i.p.) or vehicle and sacrificed 4 h later. Brain areas known to be activated by GTN administration were dissected out and utilized for the evaluation of nNOS and eNOS expression by means of western blotting. Cerebral and serum ADMA levels were measured by means of ELISA immunoassay. Cerebral DDAH-1 mRNA expression was measured by means of RT-PCR. Comparisons between experimental groups were performed using the Mann Whitney test. RESULTS: ADMA levels and nNOS expression increased in the hypothalamus and medulla following GTN administration. Conversely, a significant decrease in DDAH-1 mRNA expression was observed in the same areas. By contrast, no significant change was reported in eNOS expression. GTN administration did not induce any significant change in serum levels of ADMA. CONCLUSION: The present data suggest that ADMA accumulates in the brain after GTN administration via the inhibition of DDAH-1. This latter may represent a compensatory response to the excessive local availability of NO, released directly by GTN or synthetized by nNOS. These findings prompt an additional mediator (ADMA) in the modulation of NO axis following GTN administration and offer new insights in the pathophysiology of migraine.

Biomarkers of oxidation, inflammation and cartilage degradation in osteoarthritis patients undergoing sulfur-based spa therapies.

OBJECTIVES: To investigate the effects of sulfur-based spa therapies on oxidation, inflammation and cartilage degradation biomarkers in osteoarthritis (OA) patients. DESIGN AND METHODS: Analyses were performed before therapy (T0), after therapy (T1) and 1 month after its suspension (T2), in OA subjects undergoing mud bath treatments in combination (group A) or not (group B) with hydropinotherapy, and compared with those of patients not subjected to spa therapies (group C). RESULTS: No modifications in plasma/serum biomarker concentrations were observed throughout the study in non-treated patients, while a significant reduction in oxidation, inflammation and cartilage degradation parameters was evidenced in patients of group A. Group B presented a favorable biochemical profile at T1 but not at T2. CONCLUSIONS: To ensure the long term preservation of the chondroprotective effects of sulfur-based therapies, standard mud bath treatments should be associated with hydropinotherapy in order to maintain reduced oxidative, inflammatory and degradative stimuli longer.

Prevention of Glutamate Accumulation and Upregulation of Phospho-Akt may Account for Neuroprotection Afforded by Bergamot Essential Oil against Brain Injury Induced by Focal Cerebral Ischemia in Rat.

The effects of bergamot essential oil (BEO; Citrus bergamia, Risso) on brain damage caused by permanent focal cerebral ischemia in rat were investigated. Administration of BEO (0.1-0.5 ml/kg but not 1 ml/kg, given intraperitoneally 1 h before occlusion of the middle cerebral artery, MCAo) significantly reduced infarct size after 24 h permanent MCAo. The most effective dose (0.5 ml/kg) resulted in a significant reduction of infarct extension throughout the brain, especially in the medial striatum and the motor cortex as revealed by TTC staining of tissue slices. Microdialysis experiments show that BEO (0.5 ml/kg) did not affect basal amino acid levels, whereas it significantly reduced excitatory amino acid, namely aspartate and glutamate, efflux in the frontoparietal cortex typically observed following MCAo. Western blotting experiments demonstrated that these early effects were associated, 24 h after permanent MCAo, to a significant increase in the phosphorylation and activity of the prosurvival kinase, Akt. Indeed, BEO significantly enhanced the phosphorylation of the deleterious downstream kinase, GSK-3beta, whose activity is negatively regulated via phosphorylation by Akt.

Use of complementary and alternative medicine by patients with cluster headache: results of a multi-centre headache clinic survey.

OBJECTIVES: To evaluate the rates, pattern, satisfaction with, and presence of predictors of complementary and alternative medicine (CAM) use in a clinical population of patients with cluster headache (CH). DESIGN AND SETTING: One hundred CH patients attending one of three headache clinics were asked to undergo a physician-administered structured interview designed to gather information on CAM use. RESULTS: Past use of CAM therapies was reported by 29% of the patients surveyed, with 10% having used CAM in the previous year. Only 8% of the therapies used were perceived as effective, while a partial effectiveness was reported in 28% of CAM treatments. The most common source of recommendation of CAM was a friend or relative (54%). Approximately 62% of CAM users had not informed their medical doctors of their CAM use. The most common reason for deciding to try a CAM therapy was that it offered a "potential improvement of headache" (44.8%). Univariate analysis showed that CAM users had a higher income, had a higher lifetime number of conventional medical doctor visits, had consulted more headache specialists, had a higher number of CH attacks per year, and had a significantly higher proportion of chronic CH versus episodic CH. A binary logistic regression analysis was performed and two variables remained as significant predictors of CAM use: income level (OR=5.7, CI=1.6-9.1, p=0.01), and number of attacks per year (OR=3.08, CI=1.64-6.7, p<0.0001). CONCLUSION: Our findings suggest that CH patients, in their need of and quest for care, seek and explore both conventional and CAM approaches, even though only a very small minority finds them very satisfactory.

Antioxidant effect of sulphurous thermal water on human neutrophil bursts: chemiluminescence evaluation.

BACKGROUND: The activities of the HS (sulfhydryl or thiolic) group in the cysteine of glutathione or various low-weight soluble molecules (thiolic drugs), such as N-acethylcysteine, mesna, thiopronine and dithiotreitol or stepronine and erdosteine (prodrugs), include its antioxidant activity in the airways during the release of reactive oxygen or nitrogen species (ROS, RNS) by polymorphonuclear neutrophils (PMNs) activated in response to exogenous or endogenous stimuli. OBJECTIVE: In addition to being administered by means of thiolic molecules, the HS group can also be given by means of the inhalation of sulphurous thermal water. The aim of this study was to investigate the effect of sulphurous thermal water on the release of ROS and RNS during the bursts of human PMNs. METHODS: The luminol-amplified chemiluminescence methodology was used to investigate the ROS and RNS released by PMNs stimulated with N-formyl-methionyl-leucyl-phenylalanine and phorbol-12-myristate-13-acetate, before and after incubation with sulphurous water. Effects on cell-free systems were also investigated. RESULTS: The water significantly reduced the luminol-amplified chemiluminescence of N-formyl-methionyl-leucyl-phenylalanine- andphorbol-12-myristate-13-acetate-activated PMNs on average from 0.94 to 15.5 mug/ml of HS, even after the addition of L-arginine, a nitric oxide (NO) donor. Similar findings have also been obtained in a cell-free system, thus confirming the importance of the presence of the HS group (reductive activity). CONCLUSIONS: The positive effects of the activity of sulphurous thermal waters has been partially based on the patients' subjective sense of wellbeing and partially on not always easy to quantify symptomatic (or general) clinical improvements. Our findings indicate that, in addition to their known mucolytic activity and trophic effects on respiratory mucosa, the HS groups present in the sulphurous thermal water of this spring also have antioxidant activity that contributes to the therapeutic effects of the water in upper and lower airway inflammatory diseases.

Evaluation of thermal water in patients with functional dyspepsia and irritable bowel syndrome accompanying constipation.

AIM: To evaluate the efficacy of water supplementation treatment in patients with functional dyspepsia or irritable bowel syndrome (IBS) accompanying predominant constipation. METHODS: A total of 3872 patients with functional dyspepsia and 3609 patients with irritable bowel syndrome were enrolled in the study by 18 Italina thermal centres. Patients underwent a first cycle of thermal therapy for 21 d. A year later patients were re-evaluated at the same centre and received another cycle of thermal therapy. A questionnaire to collect personal data on social and occupational status, family and pathological case history, life style, clinical records, utilisation of welfare and health structure and devices was administered to each patient at basal time and one year after each thermal treatment. Sixty patients with functional dyspepsia and 20 with IBS and 80 healthy controls received an evaluation of gastric output and oro-cecal transit time by breath test analysis. Breath test was performed at basal time and after water supplementation therapies. Gastrointestinal symptoms were evaluated at the same time points. Breath samples were analyzed with a mass spectometer and a gascromatograph. Results were expressed as T(1/2) and T-lag for octanoic acid breath test and as oro-cecal transit time for lactulose breath test. RESULTS: A significant reduction of prevalence of symptoms was observed at the end of the first and second cycles of thermal therapy in dyspeptic and IBS patients. The analysis of variance showed a real and persistant improvement of symptoms in all patients. After water supplementation for 3 wk a reduction of gastric output was observed in 49 (87.5%) of 56 dyspeptic patients. Both T(1/2) and T-lag were significantly reduced after the therapy compared to basal values [91 +/- 12 T(1/2) and 53 +/- 11 (T-lag), Tables 1 and 2] with results of octanoic acid breath test similar to healthy subjects. After water supplementation for 3 wk oro-cecal transit time was shorter than that at the beginning of the study. CONCLUSION: Mineral water supplementation treatment for functional dyspepsia or constipation accompanying IBS can improve gastric acid output and intestinal transit time.

Use of complementary and alternative medicine by patients with chronic tension-type headache: results of a headache clinic survey.

OBJECTIVES: This study was undertaken to evaluate the rates, pattern, and presence of predictors of complementary and alternative medicine use in a clinical population of patients with chronic tension-type headache. BACKGROUND: The use of complementary and alternative medicine in the treatment of headaches is a growing phenomenon about which little is known. METHODS: A total of 110 chronic tension-type headache patients attending a headache clinic participated in a physician-administered structured interview designed to gather information on complementary and alternative medicine use. RESULTS: Past use of complementary and alternative therapies was reported by 40% of the patients surveyed (22.7% in the previous year). Chronic tension-type headache patients prefer complementary and alternative practitioner-administered physical treatments to self-treatments, the most frequently used being chiropractic (21.9%), acupuncture (17.8%), and massage (17.8%). Only 41.1% of the patients perceived complementary and alternative therapies to be beneficial. The most common source of recommendation of complementary and alternative medicine was a friend or relative (41.1%). Most of the chronic tension-type headache patients used complementary and alternative treatment as a specific intervention for their headache (77.3%). Almost 60% of complementary and alternative medicine users had not informed their medical doctors of their use of complementary and alternative medicine. The most common reasons given for choosing to use a complementary or alternative therapy was the "potential improvement of headache" it offered (45.4%). The patients who had used more complementary and alternative treatments were found to be those recording a higher lifetime number of visits to conventional medical doctors, those with a comorbid psychiatric disorder, those enjoying a higher (household) income, and those who had never tried a preventive pharmacological treatment. CONCLUSIONS: Our findings suggest that headache-clinic chronic tension-type headache patients, in their need of and quest for care, seek and explore both conventional and complementary and alternative therapies, even if only 41.1% of them perceived complementary treatments as effective. Physicians should be made aware of this patient-driven change in the medical climate in order to prevent misuse of health care resources and to be better equipped to meet patients' care requirements.

Neurophysiological approach to central pain modulation in primary headaches.

The study of CNS pain-modulating pathways has led to important discoveries about the role of central nociceptive structures such as PAG and hypothalamus in the pathophysiology of episodic and chronic primary headaches. Functional neuroimaging studies have revealed that primary headaches are characterised by different patterns of activation of central pain modulatory structures. A future model of headache pathophysiology investigating the contribution of CNS pain-modulating pathways will probably increase our understanding of pain processing in primary headaches. Herein we review the neurophysiological approaches to assess central pain modulation in primary headaches with emphasis on the diffuse noxious inhibitory control, a form of endogenous pain inhibition. In addition, patients' data will be presented that highlights the utility of such methods for primary headache's pathophysiology and clinical monitoring.

Medical healthcare use in Parkinson's disease: survey in a cohort of ambulatory patients in Italy.

BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disease which at present has no cure, and it usually results in severe disability. The burden of PD increases as the illness progresses, resulting in the extensive utilisation of both health and community services. Knowledge of healthcare use patterns and of their determinants may greatly contribute to improve patient care, however few studies have examined this issue in PD. The present study was devised to describe the type of and reasons for medical healthcare resource use in persons with PD attending a Centre for PD and Movement Disorders, and to examine drug prescriptions issued on such occasions. METHODS: The study was a retrospective, cross-sectional survey in a cohort of ambulatory patients with PD, conducted by means of standard interviews. RESULTS: In the year before the study, 92 (70.8%) of 130 patients used medical healthcare resources: 1/5 of the patients was admitted to hospital, 1/5 to emergency room, 2/5 were visited by a non-neurology specialist, and 1/4 by the GP. Reasons were: nearly 20% programmed hospital admissions and visits, and more than 25% injuries and musculo-skeletal diseases. Other conditions typically occurring in PD (e.g. dementia, diabetes and cardio- and cerebro-vascular disease) were less frequently involved. On such occasions, drugs for PD were occasionally changed, however drug prescriptions for other indications were issued to more than 66% of the patients. CONCLUSION: Several physicians other than the neurologist may take care of PD patients on different occasions, thus emphasising the need for communication between the reference neurologist and other physicians who from time to time may visit the patient.

Concomitant increase in nociceptive flexion reflex threshold and plasma opioids following transcutaneous nerve stimulation.

In order to evaluate the role of endogenous opioids in sustaining analgesia induced by transcutaneous nerve stimulation (TNS), we measured plasma beta-lipotropin (BLPH), beta-endorphin (BEP), ACTH and cortisol changes concomitantly with nociceptive flexion reflex (RIII) threshold after TNS (80 microseconds rectangular waves at 85 Hz) in a group of healthy volunteers (A). The same protocol was carried out in another group of volunteers using placebo stimulation (0.5 Hz) (B). RIII threshold significantly increased 0.5 h after TNS in group A and no changes were recorded in group B. Similarly, both BLPH and BEP plasma levels increased at the end of TNS only in group A. ACTH and cortisol concentrations show only random variations after both high and low frequency TNS. A positive linear correlation was found between the maximum percentage increase of RIII threshold after high frequency TNS and the maximum percentage increase of BLPH plasma levels occurring 20 min beforehand (r = 0.856, P less than 0.001). A less positive correlation was found between RIII and BEP levels (r = 0.574, P less than 0.05). These data indicate that the so-called post-stimulation analgesia could be supported by the enhancement of the endogenous opioid system.