Alessandra Fabrizio

Viscero-visceral hyperalgesia: characterization in different clinical models.

&NA; 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 < p < 0.05). (b) IBS + Dys had more intestinal/menstrual pain and abdomino/pelvic muscle hyperalgesia than IBS or Dys; hormonal dysmenorrhea treatment also reduced IBS symptoms; IBS dietary treatment also improved dysmenorrhea (0.001 < p < 0.05) while no treatment of either conditions resulted in no improvement in time of symptoms from both. (c) Cal + Dys had more urinary/menstrual pain and referred lumbar/abdominal hyperalgesia than Cal or Dys; hormonal dysmenorrhea treatment/laser treatment for endometriosis also improved urinary symptoms; lithotripsy for urinary stone also reduced menstrual symptoms (0.001 < p < 0.05). (d) In Gs + LCal, cholecystectomy or urinary lithotripsy did not improve urinary or biliary symptoms, respectively. Mechanisms of viscero‐visceral hyperalgesia between organs with documented partially common sensory projection probably involve sensitization of viscero‐viscero‐somatic convergent neurons.

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.

Myofascial pain syndromes and their evaluation

This article reviews the available published knowledge about the diagnosis, pathophysiology and treatment of myofascial pain syndromes from trigger points. Furthermore, epidemiologic data and clinical characteristics of these syndromes are described, including a detailed account of sensory changes that occur at both painful and nonpainful sites and their utility for diagnosis and differential diagnosis; the identification/diagnostic criteria available so far are critically reviewed. The key role played by myofascial trigger points as activating factors of pain symptoms in other algogenic conditions--headache, fibromyalgia and visceral disease--is also addressed. Current hypotheses on the pathophysiology of myofascial pain syndromes are presented, including mechanisms of formation and persistence of primary and secondary trigger points as well as mechanisms beyond referred pain and hyperalgesia from trigger points. Conventional and most recent therapeutic options for these syndromes are described, and their validity is discussed on the basis of results from clinical controlled studies.

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.

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.

Effects of Treatment of Myofascial Trigger Points on the Pain of Fibromyalgia

Myofascial pain syndromes (MPSs) from trigger points (TrPs) and fibromyalgia syndrome (FMS) are common musculoskeletal pain conditions that frequently coexist in the same patients. In recent decades, it has become evident that these entities greatly influence each other’s clinical expression. FMS is mainly rooted in the central nervous system, while TrPs have a peripheral origin. However, the nociceptive impulses from TrPs may have significant impact on symptoms of FMS, probably by enhancing the level of central sensitization typical of this condition. Several attempts have been made to assess the effects of treatment of co-occurring TrPs in FMS. We report the outcomes of these studies showing that local extinction of TrPs in patients with fibromyalgia produces significant relief of FMS pain. Though further studies are needed, these findings suggest that assessment and treatment of concurrent TrPs in FMS should be systematically performed before any specific fibromyalgia therapy is undertaken.

Effects of tramadol on viscero-visceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis

The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero‐visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague‐Dawley rats underwent surgical induction of endometriosis and, 2 weeks later, were randomly assigned to five groups (10 each), to be treated i.p., twice a day, with tramadol (0.625, 1.25, 2.5, or 5 mg/kg) or saline for 5 days (14–18th day postendometriosis; prestone treatment). On the 21st day, they underwent laparotomy for stone formation in the upper left ureter (dental cement injection). All were video‐taped 24 h nonstop for 7 days before and 4 days after stone formation (14–25th day postendometriosis) to record ureteral and pelvic pain behaviors. Lumbar sensitivity (L1) was tested bilaterally, daily over the same period, by verifying presence/absence of vocalization upon muscle pinching at a predefined pressure (calibrated forceps). Additional fifty endo + stone rats underwent the same protocol, except that treatment was performed on 21st–25th day (poststone treatment). Tramadol vs. saline significantly reduced number and duration of ureteral crises, duration of pelvic behavior, and incidence of muscle hyperalgesia (P < 0.0001), with a dose‐dependent effect. Prestone treatment was significantly more effective than poststone treatment for the 1.25 dose for all parameters and 2.5 dose for pelvic and muscle parameters (0.003 > P < 0.02). Tramadol, even at low doses, is thus highly protective against pain from ‘viscero‐visceral hyperalgesia’ in endometriosis plus ureteral calculosis; it can represent a valid therapeutic approach in women with these comorbidities.

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

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.

Impact of hypertension on somatic pain sensitivity in chronic headache

Aim of investigation Previous studies have shown that chronic headache (migraine and/or tension-type; CH) is characterized by diffuse somatic hyperalgesia, while arterial hypertension (HY) produces somatic hypoalgesia which is only partly attenuated by antihypertensive treatment. The aim of the study was to assess if comorbidity between CH and HY results into an attenuation of the hyperalgesia due to headache.

373 VISCERAL PAIN, REFERRED MUSCLE HYPERALGESIA AND THE AGING PROCESS: EXPERIMENTAL STUDY IN A RAT MODEL OF ARTIFICIAL URETHRAL CALCULOSIS

animals. Spatial firing and place field characteristics of the cells were examined before (10 days) and after (21 days) peripheral nerve injury (SNI). The findings showed an increase of the number of place fields encoded per cell and an increase of the place field size (expansion) after nerve injury. In addition, the infield coherence increases for the SNI-group and amount of spatial information (specificity) content that a single spike conveyed about the animal location decrease over time. However, other measures of spatial tuning (e.g. infield firing rate, firing peak and number of spikes) were unchanged between the two experimental groups. The current study suggests that there is a relative instability of hippocampal place cells across the installation of the peripheral pain condition in a well-trained task. Supported by FCT Grant-SFRH/BD/42500/2007 and BIAL Project126/08.