MicroRNA profiling in migraine without aura: pilot study.

BACKGROUND AND PURPOSE: MicroRNAs (miRNAs) are short, non-coding RNAs whose deregulation has been shown in several human diseases, including pain states and diseases associated with increased cardiovascular (CV) risk. This study aimed at identifying differentially expressed circulating miRNAs in patients with 'migraine without aura' (MO), a pain condition whose link with CV risk remains debated. METHODS: Fifteen female MO patients and 13 matching healthy controls underwent a circulating microRNA expression profiling. MiR-22, miR-26a, miR-26b, miR-27b, miR-29b, let-7b, miR-181a, miR-221, miR-30b, and miR-30e were selected for validation by quantitative real-time polymerase chain reaction. RESULTS: In migraineurs versus controls, four miRNAs were differentially expressed: miR-27b was significantly up-regulated (q < 0.004), while miR-181a, let-7b, and miR-22 were significantly down-regulated (q ≤ 0.01). MiR-22 and let-7b down-regulation was also confirmed in circulating blood monocytes. A logistic regression model based on microRNA expression profile showed a high accuracy for identifying migraine (AUC of ROC curve: 0.956; P < 0.001). CONCLUSION: A specific circulating miRNAs profile is associated with migraine without aura. Remarkably, the same miRNAs are known to be modulated in the setting of atherosclerosis and stroke in humans. This study represents a first step towards further characterization of MO diagnosis/pathophysiology, also in relation to its link with cardiovascular risk.

Effects of topical diclofenac plus heparin (DHEP+H plaster) on somatic pain sensitivity in healthy subjects with a latent algogenic condition of the lower limb.

OBJECTIVE: To evaluate whether a diclofenac epolamine + heparin topical (plaster) is more effective than diclofenac plaster alone in reducing deep somatic hyperalgesia in subjects without spontaneous pain and whether the effect is linked to or independent of the anti-edematous action of heparin. DESIGN: Prospective, double-blind, randomized and controlled, four-arm parallel design trial. SUBJECTS: One hundred and four patients (84 women, 20 men, mean age 42.2 ± 13.3 years), with deep somatic hyperalgesia in one thigh, randomly assigned to one of 4 groups of 26 each. INTERVENTION: Each group underwent one of the following plaster treatments on one thigh: diclofenac+heparin; diclofenac; heparin; placebo, for 7 days, renewing the plaster every 24 hours. OUTCOME MEASURES: Before treatment (day 1), at day 4 and day 8, assessment of (a) pressure and electrical pain thresholds of vastus lateralis and overlying subcutis and skin; and (b) structure/thickness of subcutis and muscle with ultrasounds at the same level. RESULTS: During treatment, in placebo and heparin, no significant threshold changes, except subcutis thresholds which increased slightly (P < 0.02); in diclofenac and diclofenac+heparin, significant increase in all thresholds (0.0001 < P < 0.04). Electrical muscle pain thresholds increased significantly more in diclofenac+heparin than in diclofenac, heparin, and placebo (0.0001 < P < 0.04). In all groups: no edema and thickness changes at ultrasounds in muscle and subcutis. CONCLUSIONS: Topical diclofenac+heparin is significantly more effective than diclofenac alone in reducing muscle hyperalgesia in subjects without spontaneous pain, independently of the anti-edematous action of heparin. The results provide a rationale for the use of diclofenac+heparin also in algogenic conditions without evident signs of injury/edema/hematoma.

Teaching neuroimages: a dangerous complication of spontaneous intracranial hypotension.

A 43-year-old man presented with a nontraumatic orthostatic headache, spatial disorientation, and visual hallucinations ("colored flames"). General and neurologic examination were normal. Turbo spin echo T2-weighted MRI showed bilateral subdural fluid collection and venous sinus engorgement (figure, A), suggesting spontaneous intracranial hypotension (SIH). Two subdural hematomas were also found, the biggest (2.5 cm) with mass effect in the left hemisphere (figure, B). Spine MRI identified a small radicular cyst emerging from the left T1-T2 foramen as the putative cause of CSF leakage (figure, C and D). The patient underwent drainage of the largest hematoma with benefit. Though initially planned, epidural blood patch and surgical treatment of the radicular cyst were not performed because clinical and radiologic findings improved with hematoma drainage, bed rest, and hydration. At a 3-month follow-up, MRI documented complete resolution of the subdural collection and dimensional stability of the radicular cyst. SIH is often considered benign and treated conservatively,(1)but it can rarely manifest with serious complications requiring rapid surgical evaluation.(2).

New insights into the cardiovascular risk of migraine and the role of white matter hyperintensities: is gold all that glitters?

The role of migraine as an independent risk factor for cardiovascular events has been debated for several years, while it is more established for ischemic stroke. Recently, new studies have examined the likelihood of migraine to determine cardiovascular events, supporting the hypothesis of a predominant role in patients with migraine with aura, the risk including both sexes. In the literature, multiple pathophysiological mechanisms are described to explain this association, and are here discussed. Furthermore, the emerging evidence that a higher headache frequency and long-term migraine may worsen the cardio-metabolic profile in migraineurs (e.g. with a higher Framingham risk score and risk of developing atherosclerosis, insulin resistance and metabolic syndrome) makes it increasingly necessary to reduce the number and severity of attacks, not only to alleviate the painful symptoms, but also to improve the prognosis in these patients.

Effectiveness of the telephonic-case-management for treatment of headache. A pilot study.

Chronic or intermittent headache affects the patients' quality of life, and has direct and indirect social costs. Several chronic illnesses are already treated through telephone counseling, however there is poor evidence in literature about headache treatment via telenursing, and it is not clear which role could the nurse play in this specific field. The study was carried out at the headache centre of "G. D'Annunzio" University - Chieti, and involved 62 patients, half of them were assigned to receive specialized telenursing in addiction to the standard care bean. During the 13 weeks of follow up the headache characteristics were regularly assessed (frequency and intensity). Pain assessment was performed using the VAS, and quality of life was assessed at baseline and at the end of the follow up using the SF-12 standard V1 questionnaire. The differences between the two groups are statistically significant during the last 5 week of follow up, (8th -12th; 0.002

Effects of treatment of peripheral pain generators in fibromyalgia patients.

Fibromyalgia syndrome (FS) frequently co-occurs with regional pain disorders. This study evaluated how these disorders contribute to FS, by assessing effects of local active vs placebo treatment of muscle/joint pain sources on FS symptoms. Female patients with (1) FS+myofascial pain syndromes from trigger points (n=68), or (2) FS+joint pain (n=56) underwent evaluation of myofascial/joint symptoms [number/intensity of pain episodes, pressure pain thresholds at trigger/joint site, paracetamol consumption] and FS symptoms [pain intensity, pressure pain thresholds at tender points, pressure and electrical pain thresholds in skin, subcutis and muscle in a non-painful site]. Patients of both protocols were randomly assigned to two groups [34 each for (1); 28 each for (2)] to receive active or placebo local TrP or joint treatment [injection/hydroelectrophoresis] on days 1 and 4. Evaluations were repeated on days 4 and 8. After therapy, in active--but not placebo-treated-- groups: number and intensity of myofascial/joint episodes and paracetamol consumption decreased and pressure thresholds at trigger/joint increased (p<0.001); FS pain intensity decreased and all thresholds increased progressively in tender points and the non-painful site (p<0.0001). At day 8, all placebo-treated patients requested active local therapy (days 8 and 11) vs only three patients under active treatment. At a 3-week follow-up, FS pain was still lower than basis in patients not undergoing further therapy and had decreased in those undergoing active therapy from day 8 (p<0.0001). Localized muscle/joint pains impact significantly on FS, probably through increased central sensitization by the peripheral input; their systematic identification and treatment are recommended in fibromyalgia.

Viscero-visceral hyperalgesia: characterization in different clinical models.

Co-existing algogenic conditions in two internal organs in the same patient may mutually enhance pain symptoms (viscero-visceral hyperalgesia). The present study assessed this phenomenon in different models of visceral interaction. In a prospective evaluation, patients with: (a) coronary artery disease (CAD)+gallstone (Gs) (common sensory projection: T5); (b) irritable bowel syndrome (IBS)+dysmenorrhea (Dys) (T10-L1); (c) dysmenorrhea/endometriosis+urinary calculosis (Cal)(T10-L1); and (d) gallstone+left urinary calculosis (Gs+LCal) (unknown common projection) were compared with patients with CAD, Gs, IBS, Dys or Cal only, for spontaneous symptoms (number/intensity of pain episodes) over comparable time periods and for referred symptoms (muscle hyperalgesia; pressure/electrical pain thresholds) from each visceral location. In patients' subgroups, symptoms were also re-assessed after treatment of each condition or after no treatment. (a) CAD+Gs presented more numerous/intense angina/biliary episodes and more referred muscle chest/abdominal hyperalgesia than CAD or Gs; cardiac revascularization or cholecystectomy also reduced biliary or cardiac symptoms, respectively (0.001

A randomized, controlled study comparing a lidocaine patch, a placebo patch, and anesthetic injection for treatment of trigger points in patients with myofascial pain syndrome: evaluation of pain and somatic pain thresholds.

BACKGROUND: Myofascial pain syndrome (MPS), a regional pain condition caused by trigger points in muscle or muscle fascia, produces muscle pain, tenderness, and disability. The gold standard of treatment for MPS-infiltration of trigger points with anesthetic-may provoke discomfort to the patients and require medical intervention. OBJECTIVES: This study was designed to compare the effects of a topical lidocaine patch, a placebo patch, and injection of anesthetic (infiltration) for the symptoms of MPS in terms of pain, disability, and local tissue hypersensitivity, and to determine the acceptability of the lidocaine patch to the patients. METHODS: Patients were randomly allocated to receive 1 of 3 treatments: a lidocaine patch applied to the trigger point for 4 days (replacement every 12 hours; total daily dose, 350 mg), a placebo patch applied to the trigger point for 4 days (replacement every 12 hours), or infiltration of the trigger point with two 1-mL injections of 0.5% bupivacaine hydrochloride given 2 days apart. Treatment with the patches was double-blinded, whereas treatment with infiltration was single-blinded. The number of pain attacks, pain intensity at rest and on movement, and pain-related interference with daily activity, work activity, mood, and quality of life were recorded before, during, and after treatment using a visual analog scale (VAS). Pressure and electrical pain thresholds of the skin, subcutis, and muscle in the trigger point, target area, and a pain-free area were evaluated before starting therapy (day 1) and on days 5 and 9. A VAS was used to measure discomfort from therapy, and a diary was given to each patient to record requests for additional treatment (if needed) and adverse effects. RESULTS: Sixty white patients (46 women and 14 men) 19 to 76 years of age were studied. Mean (SD) age was 46.88 (15.37) years, and mean (SD) weight was 69.58 (13.94) kg. Twenty patients were assigned to each treatment group. Subjective symptoms did not change with placebo, but decreased significantly with the lidocaine patch and infiltration (both, P < 0.001) relative to baseline. Pain thresholds did not vary with the placebo patch, but increased significantly with the lidocaine patch and infiltration (all, P < 0.001); effects at muscle trigger points and target areas were greater with infiltration. Discomfort from therapy was greater with infiltration than with the lidocaine patch. Only patients in the placebo group requested additional treatment (P < 0.001). No adverse events occurred in any group. CONCLUSION: Lidocaine patches were effective in, and highly acceptable to, these patients with MPS and high tissue hypersensitivity.

Contribution of myofascial trigger points to migraine symptoms.

UNLABELLED: This study evaluated the contribution of myofascial trigger points (TrPs) to migraine pain. Seventy-eight migraine patients with cervical active TrPs whose referred areas (RAs) coincided with migraine sites (frontal/temporal) underwent electrical pain threshold measurement in skin, subcutis, and muscle in TrPs and RAs at baseline and after 3, 10, 30, and 60 days; migraine pain assessment (number and intensity of attacks) for 60 days before and 60 days after study start. Fifty-four patients (group 1) underwent TrP anesthetic infiltration on the 3rd, 10th, 30th, and 60th day (after threshold measurement); 24 (group 2) received no treatment. Twenty normal subjects underwent threshold measurements in the same sites and time points as patients. At baseline, all patients showed lower than normal thresholds in TrPs and RAs in all tissues (P < .001). During treatment in group 1, all thresholds increased progressively in TrPs and RAs (P < .0001), with sensory normalization of skin/subcutis in RAs at the end of treatment; migraine pain decreased (P < .001). Threshold increase in RAs and migraine reduction correlated linearly (.0001 < P < .006). In group 2 and normal subjects, no changes occurred. Cervical TrPs with referred areas in migraine sites thus contribute substantially to migraine symptoms, the peripheral nociceptive input from TrPs probably enhancing the sensitization level of central sensory neurons. PERSPECTIVE: This article shows the beneficial effects of local therapy of active myofascial trigger points (TrPs) on migraine symptoms in patients in whom migraine sites coincide with the referred areas of the TrPs. These results suggest that migraine pain is often contributed to by myofascial inputs that enhance the level of central neuronal excitability.