Adenocarcinoma of the sigmoid colon causing sigmoido-rectal intussusception: A rare entity in adults.

INTRODUCTION: Intussusception occurs when a more proximal portion of the bowel (intussusceptum) invaginates into the more distal bowel (intussuscipiens). The pathomechanism is thought to involve altered bowel peristalsis at the intraluminal lesion, which is then a lead point for the intussusceptum. Intestinal intussusception is rare in adults, accounting for approximately 1 % of all bowel obstructions. We report a unique case in which a partially obstructing sigmoid cancer caused full thickness rectal prolapse requiring surgical intervention. PRESENTATION OF CASE: A 75-year-old male presented in the emergency department due to anal haemorrhage for 5 days. On clinical examination his abdomen was distended with signs of peritoneal irritation in the right quadrants. The CT scan showed sigmoid-rectal intussusception with an sigmoid colonic tumour. The patient underwent emergency anterior resection of the rectum without reduction of the intussusception. Histological examination revealed a sigmoid adenocarcinoma. DISCUSSION: Intussusception is the most common urgent situation among the pediatric population but its incidence in adults is very rare. The diagnosis is difficult to establish with history and physical exam findings alone. Since in adults, unlike children, in most cases a malignant pathology acts as a lead point, the treatment of this pathology still reserves doubts. Recognizing and understanding pertinent signs, symptoms, and imaging findings is essential to the early diagnosis and appropriate management of adult intussusception. CONCLUSION: The appropriate management of adult intussusception is not always clear cut. There is controversy about the reduction before resection in cases of sigmoidorectal intussusception.

Comparison between children and adults intussusception. Description of two cases and review of literature.

INTRODUCTION: Intussusception is a common condition in children, it is rare in adults. Adult intussusception differs from pediatric intussusception in various respects, including etiology clinical characteristics and therapy. METHODS: We present and discuss a new case of intussusception in children and adults. RESULTS: In child the Barium Enema x-ray examination is identified an endoluminal filling defect to refer to the apex of the invaginated loop at the rectal level, with slow ascent during the progressive injection of the radiopaque contrast medium. At the end of the procedure, incomplete reduction of the picture is documented. The patient undergoes emergency surgery where the presence of an ileo-ceco-colic invagination is documented. Intussusception is reduced by taxis. In the adult laparoscopic right hemicolectomy was performed. High-grade B-cell Burkitt's lymphoma was confirmed by immunohistochemistry. DISCUSSION: In contrast to intussusceptions in children, in the adult population, a demonstrable etiology is found in most of the cases. In adults surgery is always indicated. The non-invasive resolutive intervention most commonly used in the child and best known consists in the rectal introduction of a radiopaque contrast medium (air or barium) at controlled pressure until. CONCLUSIONS: Although intussusceptions occur at all ages, there are major differences in the clinical presentation, diagnostic approach, and management between pediatric and adult populations. Intussusception is remarkably different in these two age groups and it must be approached from a different clinical perspective. KEY WORDS: Intussusception in children, Intussusception in adults, Intussusception symptoms, Radiology and treatment.

Viscero-visceral hyperalgesia in dysmenorrhoea plus previous urinary calculosis: Role of myofascial trigger points and their injection treatment in the referred area.

BACKGROUND: Women with dysmenorrhoea plus symptomatic urinary calculosis experience enhanced pain and referred muscle hyperalgesia from both conditions than women with one condition only (viscero-visceral hyperalgesia). The study aimed at verifying if enhanced dysmenorrhoea persists after urinary stone elimination in comorbid women and if local anaesthetic inactivation of myofascial trigger points (TrPs) in the lumbar area (of urinary pain referral) also relieves dysmenorrhoea. METHODS: Thirty-one women with dysmenorrhoea plus previous urinary calculosis (Dys+PrCal) and lumbar TrPs, and 33 women with dysmenorrhoea without calculosis (Dys) underwent a 1-year assessment of menstrual pain and muscle hyperalgesia in the uterus-referred area (electrical pain threshold measurement in rectus abdominis, compared with thresholds of 33 healthy controls). At the end of the year, 16 comorbid patients underwent inactivation of TrPs through anaesthetic injections, whereas the remaining 12 received no TrP treatment. Both groups were monitored for another year at the end of which thresholds were re-measured. RESULTS: In year1, Dys+PrCal presented significantly more painful menstrual cycles and lower abdominal thresholds than Dys, thresholds of both groups being significantly lower than normal (p < .001). Anaesthetic treatment versus no treatment of the lumbar TrP significantly reduced the number of painful cycles during year2 and significantly increased the abdominal thresholds (p < .0001). CONCLUSION: Viscero-visceral hyperalgesia between uterus and urinary tract may persist after stone elimination due to nociceptive inputs from TrPs in the referred urinary area, since TrPs treatment effectively reverses the enhanced menstrual symptoms. The procedure could represent an integral part of the management protocol in these conditions. SIGNIFICANCE: A past pain process from an internal organ can continue enhancing pain expression from a painful disease in another neuromerically connected organ (viscero-visceral hyperalgesia) if secondary myofascial trigger points (TrPs) developed in the referred area at the time of the previous visceral disease. Inactivation of these TrPs reverts the enhancement. Assessment and treatment of TrPs in referred areas from past visceral pain conditions should be systematically carried out to better control pain from current diseases in other viscera.

Acute headache management in emergency department. A narrative review.

Headache is a significant reason for access to Emergency Departments (ED) worldwide. Though primary forms represent the vast majority, the life-threatening potential of secondary forms, such as subarachnoid hemorrage or meningitis, makes it imperative for the ED physician to rule out secondary headaches as first step, based on clinical history, careful physical (especially neurological) examination and, if appropriate, hematochemical analyses, neuroimaging or lumbar puncture. Once secondary forms are excluded, distinction among primary forms should be performed, based on the international headache classification criteria. Most frequent primary forms motivating ED observation are acute migraine attacks, particularly status migrainous, and cluster headache. Though universally accepted guidelines do not exist for headache management in an emergency setting, pharmacological parenteral treatment remains the principal approach worldwide, with NSAIDs, neuroleptic antinauseants, triptans and corticosteroids, tailored to the specific headache type. Opioids should be avoided, for their scarce effectiveness in the acute phase, while IV hydration should be limited in cases of ascertained dehydration. Referral of the patient to a Headache Center should subsequently be an integral part of the ED approach to the headache patients, being ascertained that lack of this referral involves a high rate of relapse and new accesses to the ED. More controlled studies are needed to establish specific protocols of management for the headache patient in the ED.

A case of Type 2 appendiceal diverticulum perforated and a review of the literature.

BACKGROUND: Appendiceal diverticulosis disease is a rare entity. An perforated appendiceal diverticulosis mimicking acute appendicitis is a extremely unusual surgical finding and the reported prevalence is between 0.014 and 3.7%. CASE REPORT: We report the case of an elderly man, who presented with a typical clinical image of acute appendicitis and underwent laparoscopic surgery. Intraoperative an acute appendicitis with localized peritonitis was identified and a laparoscopic appendectomy was performed, but pathologic analysis demonstrated a type 2 appendiceal diverticulitis. CONCLUSION: Appendiceal diverticulosis disease should be included in differential diagnosis of patients presenting with clinical signs of an acute appendicitis and prompt surgical treatment is essential in order to avoid severe complications.

Co-occurrence of pain syndromes.

Many pain conditions in patients tend to co-occur, influencing the clinical expressions of each other in various ways. This paper summarizes the main concurrent pain conditions by analyzing the major interactions observed. In particular, co-occurrence will be examined in: visceral pain (especially ischemic heart disease, irritable bowel syndrome, dysmenorrhea/endometriosis and urinary pain), fibromyalgia, musculoskeletal pain and headache. Two concurrent visceral pains from internal organs sharing at least part of their central sensory projection can give rise to viscero-visceral hyperalgesia, i.e., enhancement of typical pain symptoms from both districts. Visceral pain, headache and musculoskeletal pains (myofascial pain from trigger points, joint pain) can enhance pain and hyperalgesia from fibromyalgia. Myofascial pain from trigger points can perpetuate pain symptoms from visceral pain conditions and trigger migraine attacks when located in the referred pain area from an internal organ or in cervico-facial areas, respectively. The pathophysiology of these pain associations is complex and probably multifactorial; among the possible processes underlying the mutual influence of symptoms recorded in the associations is modulation of central sensitization phenomena by nociceptive inputs from one or the other condition. A strong message in these pain syndrome co-occurrence is that effective treatment of one of the conditions can also improve symptoms from the other, thus suggesting a systematic and thorough evaluation of the pain patient for a global effective management of his/her suffering.

Effects of topical vs injection treatment of cervical myofascial trigger points on headache symptoms in migraine patients: a retrospective analysis.

BACKGROUND: In migraine patients with cervical myofascial trigger points whose target areas coincide with migraine sites (M + cTrPs), TrP anesthetic injection reduces migraine symptoms, but the procedure often causes discomfort. This study evaluated if a topical TrP treatment with 3% nimesulide gel has similar efficacy as the injection but produces lesser discomfort with higher acceptability by the patients. METHODS: Retrospective analysis of medical charts of M + cTrPs patients in the period January 2012-December 2016 at a single Headache Center. Three groups of 25 patients each were included, all receiving migraine prophylaxis (flunarizine 5 mg/day) for 3 months and symptomatic treatment on demand. Group 1 received no TrP treatment, group 2 received TrP injections (bupivacaine 5 mg/ml at basis, 3rd, 10th, 30th and 60th day), group 3 received daily TrP topical treatment with 1.5 g of 3% nimesulide gel for 15 consecutive days, 15 days interruption and again 15 consecutive days. The following were evaluated: monthly number of migraine attacks and rescue medications, migraine intensity; pain thresholds to skin electrical stimulation (EPTs) and muscle pressure stimulation (PPTs) in TrP and target (basis, 30th, 60th and 180th days); discomfort from, acceptability of and willingness to repeat treatment (end of study). ANOVA for repeated measures and 1-way ANOVA were used to assess temporal trends in each group and comparisons among groups, respectively. Significance level was set at p < 0.05. RESULTS: Migraine improved over time in all groups, but significantly more and earlier in those receiving TrP treatment vs no TrP treatment (0.02 < p < 0.0001, 30-180 days for intensity and rescue medication, 60-180 days for number). All thresholds in the non-TrP-treated group did not change over time, while significantly improving in both the injection and nimesulide gel groups (0.01 < p < 0.0001, 30-180 days). Improvement of migraine and thresholds did not differ in the two TrP-treated groups. Discomfort was significantly lower, acceptability and willingness to repeat treatment significantly higher (0.05 < p < 0.0001) with gel than injection. CONCLUSION: In migraine patients, topical treatment of cervical TrPs with 5% nimesulide gel proves equally effective as TrP injection with local anesthetics but more acceptable by the patients. This treatment could be effectively associated to standard migraine prophylaxis to improve therapeutic outcomes.

Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab.

Migraine is a highly disabling neurological condition, and preventative treatment still remains problematic, due to aspecificity of the majority of the currently available prophylactic drugs. Calcitonin-gene-related peptide (CGRP) plays a crucial role in migraine pathophysiology; agents aimed at blocking its activity have, therefore, been developed in recent years, among which are monoclonal antibodies (mAbs) against CGRP, to prevent migraine. Erenumab is the only mAb that targets the CGRP receptor instead of the ligand, with high specificity and affinity of binding. This review will report on the most recent data on erenumab characteristics and on the results of clinical trials on its employment in the prevention of episodic migraine (4-14 monthly migraine days): one Phase II and two Phase III trials (completed) and one Phase III trial (ongoing). Monthly subcutaneous administration (70 mg or 140 mg) of erenumab vs placebo for 3-6 months showed significantly higher efficacy in reducing the mean monthly number of migraine days and the use of migraine-specific medication, and in decreasing physical impairment and impact of migraine on everyday activities (P<0.001). A favorable safety profile was demonstrated by the lack of significant differences in the occurrence of adverse events in erenumab-treated vs placebo-treated patients. Global results so far obtained point to erenumab as a new promising candidate for the preventative treatment of episodic migraine. Licence applications for erenumab were recently submitted to the Food and Drug Administration in the USA and European Medicines Agency in Europe (May/June 2017).

Visceral pain as a triggering factor for fibromyalgia symptoms in comorbid patients.

Fibromyalgia syndrome (FMS) is a central sensitization syndrome; however, peripheral pain sources potentially exacerbate its symptoms of chronic diffuse musculoskeletal pain and hyperalgesia. This prospective study evaluated visceral pain as a possible triggering factor for FMS pain and hyperalgesia in comorbid patients. Women with (1) FMS + irritable bowel syndrome (IBS); (2) FMS + primary dysmenorrhea (Dys); (3) FMS + Dys secondary to endometriosis (Endo); (4) FMS + colon diverticulosis (Div) were compared with FMS-only women, for fibromyalgia pain (number and intensity of episodes and analgesic consumption) over comparable periods and for somatic hyperalgesia (electrical and pressure pain thresholds) in painful (tender points) and control areas (trapezius, deltoid, quadriceps muscles, and overlying subcutis and skin). In comorbid subgroups, FMS symptoms were also reassessed after treatment of the visceral condition or no treatment. All comorbid groups vs FMS-only had significantly higher FMS pain (number/intensity of episodes and analgesic consumption) and hyperalgesia in deep somatic tissues (subcutis and muscle) at all sites (0.05 < P < 0.0001). Visceral pain (number of IBS days, painful menstrual cycles, and abdominal pain episodes from diverticulitis) correlated directly with all parameters of FMS pain and inversely with muscle pain thresholds at all sites (0.03 < P < 0.0001). Fibromyalgia syndrome pain and hyperalgesia in all tissues and all sites significantly decreased in patients after visceral comorbidity treatment (dietary for 6 months [IBS], hormonal for 6 months [dysmenorrhea], laser [endometriosis], and surgery [diverticulosis]) (0.05 < P < 0.0001) vs no change in untreated patients. Visceral pain enhances FMS symptoms, probably augmenting the level of central sensitization typical of the syndrome. Systematic assessment and treatment of visceral pain comorbidities should be a part of FMS management strategy.

Use of Nonsteroidal Anti-Inflammatory Drugs for Symptomatic Treatment of Episodic Headache.

INTRODUCTION: Primary headaches have high epidemiologic impact but their symptomatic treatment often remains problematic. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used, but their modality of employment and efficacy/differential efficacy are highly variable. This study investigated current NSAID use for episodic headache at an Italian headache center (January 2000 to February 2013). METHODS: A retrospective evaluation was performed on 6,443 patient records: migraine (n = 2,330), tension-type headache (TTH; n = 807), and migraine plus TTH (n = 3,306). RESULTS: Among migraine patients, 80% had used NSAIDs in the past year. Preferences were: nimesulide (57%), ketoprofen (25%), and ibuprofen (24%); complete efficacy was significantly higher than incomplete/absent efficacy (P < 0.0001). NSAIDs were replaced with triptans in 53% of patients at first visit; after 1 year there was a spontaneous significant return to NSAIDs (56%; P < 0.0005). Among TTH patients, 90% were NSAID users; preferences were: nimesulide (48%), ketoprofen (47%), and diclofenac (19%), with significantly higher complete vs. incomplete/absent efficacy (nimesulide and ketoprofen, P < 0.02). Replacement with analgesics was performed in 24% of patients; after 1 year, there was a 29% return to NSAIDs. Among migraine plus TTH patients, 89% were NSAID users. Preferences were: nimesulide (44%), ibuprofen (42%), and ketoprofen (38%), with significantly higher complete vs. incomplete/absent efficacy (0.001 < P < 0.0001). Replacement with analgesics was performed in 31% of patients; after 1 year, there was a 37% return to NSAIDs. CONCLUSIONS: Nonsteroidal anti-inflammatory drug use in headache was higher than could be hypothesized based on guidelines, with NSAID preferences not entirely coinciding with international recommendations. This outcome suggests the need for greater awareness of all treatment options in headache by both patients and physicians.

Anti-CGRP monoclonal antibodies in migraine: current perspectives.

Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration. Monoclonal antibodies against CGRP (LY2951742, ALD-403, and LBR-101/TEV-48125) or its receptor (AMG334) were subsequently developed. As reviewed in this study, numerous phase 1 and 2 trials and preliminary results of phase 3 trials have shown a good safety/tolerability profile and efficacy in migraine prevention, especially in high frequent episodic and chronic forms. Being macromolecules, these mAbs are not suitable for oral administration; however, their intravenous or subcutaneous delivery can be performed at relatively low frequency-every month or even quarterly-which enhances patients' compliance. Although not all migraineurs respond to this treatment, and longer administration periods will be needed to assess long-term effects, the results so far obtained are extraordinarily promising. The future introduction of mAbs on the market will probably represent a turning point for prevention similar to that represented by triptans for abortive treatment in migraine.

Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization.

Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale) and pain thresholds in tender points and control areas (skin, subcutis and muscle) were evaluated 1week before (basis) and 1week, 1,3,6 and 12months after laparoscopic cholecystectomy in fibromyalgia patients with symptomatic calculosis (n = 31) vs calculosis patients without fibromyalgia (n. 26) and at comparable time points in fibromyalgia patients not undergoing cholecystectomy, with symptomatic (n = 27) and asymptomatic (n = 28) calculosis, and no calculosis (n = 30). At basis, fibromyalgia+symptomatic calculosis patients presented a significant linear correlation between the number of previously experienced biliary colics and fibromyalgia pain (direct) and muscle thresholds (inverse)(p<0.0001). After cholecystectomy, fibromyalgia pain significantly increased and all thresholds significantly decreased at 1week and 1month (1-way ANOVA, p<0.01-p<0.001), the decrease in muscle thresholds correlating linearly with the peak postoperative pain at surgery site (p<0.003-p<0.0001). Fibromyalgia pain and thresholds returned to preoperative values at 3months, then pain significantly decreased and thresholds significantly increased at 6 and 12months (p<0.05-p<0.0001). Over the same 12-month period: in non-fibromyalgia patients undergoing cholecystectomy thresholds did not change; in all other fibromyalgia groups not undergoing cholecystectomy fibromyalgia pain and thresholds remained stable, except in fibromyalgia+symptomatic calculosis at 12months when pain significantly increased and muscle thresholds significantly decreased (p<0.05-p<0.0001). The results of the study show that biliary colics from gallbladder calculosis represent an exacerbating factor for fibromyalgia symptoms and that laparoscopic cholecystectomy produces only a transitory worsening of these symptoms, largely compensated by the long-term improvement/desensitization due to gallbladder removal. This study provides new insights into the role of visceral pain comorbidities and the effects of their treatment on fibromyalgia pain/hypersensitivity.

Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis: role of mast cells.

The effects of ultramicronized palmitoylethanolamide were evaluated on pain behaviours and markers of mast cell (MC) activity in a rat model of endometriosis plus ureteral calculosis (ENDO+STONE)-induced viscerovisceral hyperalgesia (VVH). Female Sprague-Dawley rats that underwent surgical induction of endometriosis were randomly assigned to receive active (ultramicronized palmitoylethanolamide 10 mg·kg(-1)·d(-1), orally) or placebo treatment for 25 days. At day 21, they underwent ureteral stone formation and were video-recorded till day 25 to evaluate ureteral and uterine pain behaviours. At autopsy (day 25), ureteral condition and number and diameter of endometrial cysts were evaluated. The following were then measured: number and percentage of degranulating MCs, number of vessels, chymase, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and Flk-1 (VEGF receptor) in cysts, and NGF in dorsal root ganglia (DRG). Ultramicronized palmitoylethanolamide-treated vs placebo-treated rats showed significantly lower number, duration and complexity of ureteral crises, shorter duration of uterine pain, and smaller cyst diameter (0.0001 < P < 0.004); a significantly higher percentage of expelled stones (P < 0.0001); significantly lower MC number (P < 0.01), vessel number (P < 0.01), chymase (P < 0.05), NGF (P < 0.05), VEGF (P < 0.01), and Flk-1 (P < 0.01) expression in cysts and NGF expression in DRG (P < 0.01). In all animals, the global duration of ureteral crises correlated linearly and directly with cyst diameter, MC number and chymase in cysts, and NGF in cysts and DRG (0.02 < P < 0.0002). Ultramicronized palmitoylethanolamide significantly reduces VVH from ENDO+STONE, probably by modulating MC expression/activity in cysts, thus reducing central sensitization due to noxious signals from endometriotic lesions. The results suggest potential utility of the compound for VVH in clinics.

Effects of PDE5 Inhibitors and sGC Stimulators in a Rat Model of Artificial Ureteral Calculosis.

Urinary colics from calculosis are frequent and intense forms of pain whose current pharmacological treatment remains unsatisfactory. New and more effective drugs are needed to control symptoms and improve stone expulsion. Recent evidence suggested that the Nitric Oxide (NO) / cyclic guanosine monophosphate (cGMP)/phosphodiesterase type 5 (PDE5) system may contribute to ureteral motility influencing stone expulsion. We investigated if PDE5 inhibitors and sGC stimulators influence ureteral contractility, pain behaviour and stone expulsion in a rat model of ureteral calculosis. We investigated: a) the sex-specific PDE5 distribution in the rat ureter; b) the functional in vitro effects of vardenafil and sildenafil (PDE5 inhibitors) and BAY41-2272 (sGC stimulator) on induced ureteral contractility in rats and c) the in vivo effectiveness of vardenafil and BAY41-2272, alone and combined with ketoprofen, vs hyoscine-N-butylbromide alone or combined with ketoprofen, on behavioural pain indicators and stone expulsion in rats with artificial calculosis in one ureter. PDE5 was abundantly expressed in male and female rats' ureter. In vitro, both vardenafil and BAY41-2272 significantly relaxed pre-contracted ureteral strips. In vivo, all compounds significantly reduced number and global duration of "ureteral crises" and post-stone lumbar muscle hyperalgesia in calculosis rats. The highest level of reduction of the pain behaviour was observed with BAY41-2272 among all spasmolytics administered alone, and with the combination of ketoprofen with BAY41-2272. The percentage of stone expulsion was maximal in the ketoprofen+BAY41-2272 group. The NO/cGMP/PDE5 pathway is involved in the regulation of ureteral contractility and pain behaviour in urinary calculosis. PDE5 inhibitors and sGC stimulators could become a potent new option for treatment of urinary colic pain.

Impact of migraine on fibromyalgia symptoms.

BACKGROUND: Fibromyalgia (FMS) and high frequency episodic/chronic migraine (M) very frequently co-occur, suggesting common pathophysiological mechanisms; both conditions display generalized somatic hyperalgesia. In FMS-M comorbidity we assessed if: a different level of hyperalgesia is present compared to one condition only; hyperalgesia is a function of migraine frequency; migraine attacks trigger FMS symptoms. METHODS: Female patients with fibromyalgia (FMS)(n.40), high frequency episodic migraine (M1)(n.41), chronic migraine (M2)(n.40), FMS + M1 (n.42) and FMS + M2 (n.40) underwent recording of: -electrical pain thresholds in skin, subcutis and muscle and pressure pain thresholds in control sites, -pressure pain thresholds in tender points (TePs), -number of monthly migraine attacks and fibromyalgia flares (3-month diary). Migraine and FMS parameters were evaluated before and after migraine prophylaxis, or no prophylaxis, for 3 months with calcium-channel blockers, in two further FMS + H1 groups (n.49, n.39). 1-way ANOVA was applied to test trends among groups, Student's t-test for paired samples was used to compare pre and post-treatment values. RESULTS: The lowest electrical and pressure thresholds at all sites and tissues were found in FMS + M2, followed by FMS + H1, FMS, M2 and M1 (trend: p < 0.0001). FMS monthly flares were progressively higher in FMS, FMS + M1 and FMS + M2 (p < 0.0001); most flares (86-87 %) occurred within 12 h from a migraine attack in co-morbid patients (p < 0.0001). Effective migraine prophylaxis vs no prophylaxis also produced a significant improvement of FMS symptoms (decreased monthly flares, increased pain thresholds)(0.0001 < p < 0.003). CONCLUSIONS: Co-morbidity between fibromyalgia and migraine involves heightened somatic hyperalgesia compared to one condition only. Increased migraine frequency - with shift towards chronicity - enhances both hyperalgesia and spontaneous FMS pain, which is reversed by effective migraine prophylaxis. These results suggest different levels of central sensitization in patients with migraine, fibromyalgia or both conditions and a role for migraine as a triggering factor for FMS.

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.

Pain thresholds in women with chronic pelvic pain.

PURPOSE OF REVIEW: To update on the latest developments in sensory changes of female patients with chronic pelvic pain (CPP). CPP is very common, but its pathophysiology is still controversial. Evaluation of pain sensitivity in painful and nonpainful areas is key to understanding the underlying peripheral vs. central contributions to the symptom. This in turn is fundamental to improving the treatment strategies. RECENT FINDINGS: We reviewed the experimental studies published over the last year on pain thresholds to different stimuli measured at both the somatic and visceral level in women with different forms of recurrent or CPP. The majority of the studies indicate a pain threshold decrease to most stimuli in skin, subcutis and muscle in painful pelvic areas, the site of referred pain from pelvic viscera, as well as a decreased pain threshold in most viscera (colon and urinary bladder). A significant threshold decrease is also found in deep somatic tissues (subcutis and muscle) outside the painful zone in the most severe cases, indicating a state of central sensitization. SUMMARY: These findings have important implications for clinical practice: pain threshold measurement in both painful and nonpainful sites could have important predictive value of the clinical evolution and response to therapy of CPP.