Skeletal Pain Research Articles

AB0567 Coexistence of spondyloarthropathy and hypermobility joint syndrome: a report of seven cases

BackgroundSpondyloarthropathies manifest with axial skeletal pain, stiffness and loss of mobility, whereas, Hypermobility Joint Syndromes, most commonly Benign Joint Hypermobility Syndrome (BJHS), Marfan’s syndrome, and Ehler’s Danlos syndrome (EDS), manifest...

Osteoporosis and related factors in older females with skeletal pain or numbness: A retrospective study in East China

To analyse relationships between incidence of osteoporosis, age and clinical symptoms in older female patients in East China. Data from females aged ≥ 30 years, admitted to QiLu Hospital between January 1999 and December 2011 were retrospectively assessed for osteoporosis. Correlations between osteoporosis diagnosis, age and clinical symptoms were analysed. Factors associated with osteoporosis were assessed using logistic regression. Out of 4212 patients enrolled, 1673 were assigned to the osteoporosis group and 2539 to the nonosteoporosis group. Neck, shoulder and arm pain negatively correlated with osteoporosis diagnosis. Lumbar and back pain had no correlation with osteoporosis diagnosis. In patients with osteoporosis there was no relationship between bone density and site of clinical symptoms. Bone density decreased, as age increased, in patients aged >50 years in the osteoporosis group. The present study revealed a relationship between epidemiological distribution of osteoporosis and associated factors in adult females suffering from pain or numbness, in East China.

Preparation and characterization of repaglinide loaded ethylcellulose nanoparticles by solvent diffusion technique using high pressure homogenizer

ObjectiveAn oral hypoglycemic agent repaglinide has less bioavailability and half-life. Its repeated dosing may cause side effects like headache, skeletal muscle pain and gastrointestinal effects. To overcome these problems, a sustained release nanoparticles has designed to maintain constant level of a drug in the patient's blood stream. Materials and methodsThe sustained released nanoparticles were prepared by Solvent emulsion diffusion technique using ethylcellulose as carrying material. Drug and polymer at different ratios were dissolved in ethyl acetate. To reduce size high pressure homogenizer was used. Final freeze dried nanoparticles used for characterization. ResultsThe obtained nanoparticles sizes 90.48 nm, 148.4 nm, 240.7 nm were increased in order of polymer concentrations. There encapsulation efficiency was up to 97.66 ± 0.88% in higher drug-polymer ratio. Infrared spectroscopy proved that there was not interaction between repaglinide and ethylcellulose. X-ray diffraction observed the crystallinity of recovered nanoparticles was less than pure repaglinide. The obtained nanoparticles sustained 11.24 ± 0.06 to 18.32 ± 0.12% repaglinide up to 12 h. The mechanism of drug release was Anomalous/non-Fickian diffusion. ConclusionSaturated ethylcellulose ethyl acetate solution facilitates efficient encapsulation of repaglinide at 0.5% PVA. The drug release mechanism is combination of diffusion and erosion. This formulation can increase patient compliance by reduce the number of dosage and incidence of side effects.

Vitamin D deficiency is associated with nonspecific skeletal pain in Saudi women

Vitamin D deficiency is associated with nonspecific skeletal pain in Saudi women

EVALUATION OF POLYHERBAL FORMULATION FOR ANTI-INFLAMMATORY ACTIVITY IN CARRAGEENAN INDUCED PAW OEDEMA MODEL IN RATS

Dazzle Capsule, a Poly herbal formulation is marketed i n management of Arthritis and joint - musculo skeletal pain . In this study, safety and efficacy of this polyherbal formulation was investigated in whi ch it wa s being proved safe for use via acute toxicity study and e fficacy was being evaluated by carrageenan - induced rat paw o edema test in rats in order to explore its anti - inflammatory activity at the dose level of 90 and 180 mg/kg, p.o , comp ared with In domethacin (10 mg/kg, p.o.) . It showed an highly significant reduction in o edema (p<0.001). Indomethacin inhibited o edema by 30.054 % and 36.216 % at 2 and 3 h r after carrageenan injection, respectively. The inhibitory effect of Dazzle Capsule began at 2 h r or later after carrageenan injection depending upon the administered dose. Low doses of Dazzle Capsule ( 90 mg/kg) gave highly significant inhibitory effects of 37.894 - 39.378% , and higher doses (180 mg/kg) caused highly significant inhibition of 19.125 - 30 % . The reduction of o edema by Indomethacin and Dazzle Capsule at 2 h r or more after carrageenan injection suggest ed that both compounds produce anti - inflammatory effects in the second phase of o edema, indicating inhibition of prostaglandin synthesis. Hence , i t was concluded that, Dazzle Capsule is having potent anti - inflammatory activity yet safe polyherbal formulation for use in arthritis management .

Abstract 2082: PKC412 (Midostaurin) is safe and highly effective in Systemic Mastocytosis patients: the Bologna experience.

Abstract Introduction. Mastocytosis is a myeloid neoplasm characterized by abnormal accumulation and frequent activation of mast cells (MCs) in various organs, mostly bone marrow, skin, liver and gastrointestinal tract. In most adult patients, the systemic form of mastocytosis (SM) is diagnosed, which includes an indolent (ISM), an aggressive (ASM) and a leukemic subvariant (MCL). The c-kit mutation D816V is detectable in most adult patients with SM. Treatment of SM usually focuses on symptom relief by histamine receptor antagonists and other supportive therapy. However, in aggressive and leukemic variants, cytoreductive and targeted drugs must be applied. Methods. From 2008, 18 patients (male/female=7/11) affected by SM, have been referred to our Institution. The median age was 49 years. All the patients underwent a bone marrow biopsy, with flow citometry and molecular biology analysis, in order to identify the presence of D816V mutation of c-Kit gene. Serum tryptase level was tested, resulting elevated in all cases. Systemic symptoms were characterized by nausea, diarrhoea, asthenia, weight loss, pruritus and serotine fever, identifying an aggressive form of the disease in 7/18 patients, due to skeletal involvement, ascitis, liver function impairment, and bone marrow disfunction. Therefore, since a first line therapy (mainly represented by IFN) and supportive care with histamine receptor antagonists werne't followed by a significant benefit, a personalized use of PKC412 was asked and obtained for 5 out of 7 ASM patients. Results. From March 2011 5 out of 7 patients with ASM have received a prolonged period of treatment with PKC412, which was administered orally, at the dosage of 100 mg twice daily, without rest periods. The drug was well tolerated. No serious adverse events were observed. All the patients obtained a quick and prolonged improvement of clinical symptoms, in terms of weight gain, bowel function and skeletal pain. At the bone marrow evaluation, the persistence of the D816V c-kit mutation was observed, despite a significant decrease of mast cell marrow involvement. In one case we observed, after a first good response, a disease progression, characterized by the sudden reoccurrence of the same symptoms detected at diagnosis, confirmed by a relevant expansion of a pathologic mast cell population in the bone marrow. After a rest period, the drug was readministered, and a second remission was obtained. Conclusions. PKC412 is safe and effective in patients with SM, being able to significantly improve not only the gastrointestinal and systemic symptoms, but also the haematological profile. The persistence of the D816V c-kit mutation, despite a morphologic remission, suggests that many other oncogenic factors may be responsible for the pathogenesis of the disease. Acknowledgments. Work supported by European LeukemiaNet, AIRC, AIL, PRIN, University of Bologna and BolognAIL. Citation Format: Cristina Papayannidis, Mariachiara Abbenante, Sarah Parisi, Stefania Paolini, Ilaria Iacobucci, Emanuela Ottaviani, Anna Ferrari, Viviana Guadagnuolo, Chiara Sartor, Simona Soverini, Caterina De Benedittis, Carmen Baldazzi, Michele Baccarani, Michele Cavo, Giovanni Martinelli. PKC412 (Midostaurin) is safe and highly effective in Systemic Mastocytosis patients: the Bologna experience. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2082. doi:10.1158/1538-7445.AM2013-2082

Pro‐osteolytic effects of chronic morphine administration in a model of breast cancer‐induced bone pain.

Many common cancers have a high propensity for bone metastasis; for breast cancer, bone metastasis affects 70% of advanced patients and is the most common site for secondary tumor relapse. Tumor manifestation disrupts bone homeostasis and results in debilitating chronic skeletal pain that decreases patient functional status, quality of life and survival. Morphine remains the golden standard for managing cancer‐induced bone pain; however, opioids including morphine are associated with a host of side effects that complicate chronic dosing schedules. Furthermore, it has been posited that morphine may accelerate bone wasting in patients; in models of secondary bone metastasis, morphine exacerbates fracture rate, markers of osteolysis, and pain behaviors.We sought to determine whether morphine exacerbates bone loss in the 66.1‐Balb/C model of breast cancer‐induced bone metastasis (BCBM). Sham and tumor‐inoculated animals received a constant morphine infusion for 7 days (20 mg/kg/day). Morphine produced initial analgesia but failed to manage behaviors indicative of cancer‐induced bone pain over time; additionally, morphine treatment increased TRACP 5b in sera and RANKL in femur extrudate, suggesting that morphine enhances osteolysis in BCBM. In vitro studies evaluated the ability of morphine to induce osteoclastogenesis in the presence of permissive levels of RANKL. Morphine did not appear to affect tumor burden in vivo or in vitro viability of tumor cells. These data suggest that morphine worsens bone loss in the 66.1‐Balb/C model and may act directly on osteoclast cells; however, the exact mechanism of morphine‐induced bone loss is unknown and remains a barrier to improving pain relief in suffering BCBM patients.

Isolated adrenal hemorrhage after blunt trauma: Case report and literature review

Isolated adrenal hemorrhage following blunt abdominal trauma is rare. The wide variation in clinical manifestations and lack of specific biologic markers make its diagnosis difficult. Computed tomography (CT) remains the golden standard for detecting this injury. Although isolated adrenal hemorrhage is usually silent and self-limiting, the presence of adrenal hemorrhage in a patient with trauma is associated with higher injury severity, and coexisting injury to the liver, ribs, kidneys, or spleen is common. Blunt trauma-related acute thoracoabdominal pain and skeletal pain are common problems in the emergency room. Patients should be carefully evaluated according to their trauma mechanism and physical examination. If an unusual complaint is presented (e.g., pain associated with cold seating or pain persisting after general analgesics), the emergency room physician should be aware of adrenal injury, the possibility of associated organ injury, and the potential for adrenal insufficiency. It is also necessary for clinicians to become familiar with common diagnostic tools, treatment options, and trends for noninvasive procedures. Prompt recognition of associated injuries and the potential for mortality with adrenal insufficiency can provide the best guidance for patient treatment and care. In this article, we present the report of a 32-year-old male, who suffered from blunt chest trauma and complained of ill-defined chest pain associated with cold seating. His CT results revealed a left adrenal hemorrhage with a large retroperitoneal hematoma. The patient was treated successfully with conservative observation.

Association between mutations of SCN9A gene and pain related to Parkinsonism

To screening mutations of exons 15, 18 and 26 of sodium channel Nav1.7 (SCN9A) gene, and to assess its association with pain related to Parkinsonism. Respectively, 101 patients with primary Parkinson's disease (PD) and 104 similar-aged volunteers without PD were recruited from March, 2008 to January, 2011. Mutations of above 3 exons in SCN9A gene was detected with PCR and direct sequencing. For 100 patients with Parkinsonism, the pain was scored with a McGill pain rating scale. Statistical analysis was performed with SPSS. The prevalence of pain in Parkinsonian was 57%. 43.86% patients with pain were males, and 56.14% were females. Based on Chaudhuri criteria, the pain symptoms may be classified as musculoskeletal pain (10.52%), radicular pain (10.52%), dyskinesis pain (54.38%), pain from akathisia and restlessness (14.04%), dyskinesis combined with radicular pain (5.26%), skeletal muscles pain and headache (1.75%), and arthralgia (3.50%). Two missense mutations were identified, which included 2794A/C (0.941/0.059) (rs12478318) (M932L) in exon 15 and 3448C/T (0.988/0.012) (rs6746030) (R1150W) in exon 18. The wild type A/C for the 2794 locus had a higher prevalence in PD patients with pain, but this was not statistically different. All of the 5 heterozygotes for 3448 (C/T) were found in Parkinsonian patients with pain. No homozygotes were found. The prevalence of pain was higher in Parkinsonian patients than general population, and the proportion of males to females was similar. More patients have suffered dyskinesis pain. A 3448 (C/T) mutation of SCN9A gene may be related to pathogenesis of pain in Parkinsonism.

Formulation and Evaluation of Oral Disintegrating Tablets of Lornoxicam by 32 Factorial Design

Article history: Received on: 24/07/2013 Revised on: 18/08/2013 Accepted on: 13/09/2013 Available online: 18/09/2013 Oral disintegrating dosage form provides an opportunity to manufacturers to extend product life cycle and to expand market. Oral disintegrating tablets (ODT) have this opportunity over conventional tablets. Lornoxicam is non steroidal anti-inflammatory drug and used in treatment of post traumatic pains, muscular and skeletal pains, joint disorder and rheumatic arthritis. Fast onset of action is required in these indications. Therefore it was thought to prepare ODT of Lornoxicam which would help to avoid first pass metabolism and to improve bioavailability as well. ODT were prepared by direct compression method by using crospovidone as superdisintegrating agent and optimized by 3 factorial design. Independent variables were concentration of crospovidone (X1) and hydroxypropyl cellulose (X2) while dependent variables were disintegration time and percent drug released. Optimised formulation, F4, showed drug content (97.90±0.37%), disintegration time (20.33±0.317 sec), percent drug released (101.5±0.59%), water absorption ratio (113.5±1.26%). This formulation was stable at 40C ±2C and RH 75%±5% for three months. Present study demonstrated potential for rapid absorption, improved bioavailability, effective therapy and patient compliance.

The potential therapeutic targets to bone pain induced by cancer metastasis

About 75-90% of patients with advanced metastatic cancer experience significant cancer pain. Bone cancer pain is one of the most common pains experienced by patients with advanced breast, prostate, or lung cancer. It is characterized by significant skeletal remodeling, fractures, pain, and anemia, all of which reduce the functional status, quality of life, and survival of the patient. Recent years have seen great progress toward alleviating bone pain with the identification of a range of chemicals as well as receptors modulating cancer pain progression. However, the complicated interactions among these factors and, sometimes, the contradicting effects of the same factor in different pathways make it difficult to spot individual effective targets. The sheer quantity of the chemicals involved and the limited understanding from animal models are the constraints in the development of effective therapies for cancer bone pain. In this review, key targets will be discussed along the pain transduction pathway, including peripheral pain sensation, spinal cord transduction pathway, and the central nervous system, to offer a logical and systematic study for the development of combined anti-bone pain treatments.

Clinical and Biochemical Profile of Monoclonal Gammopathies in Caribbean Patients in a Resource-limited Setting

Multiple myeloma is the most common malignant plasma cell dyscrasia and ranks second among primary haematological malignancies. This study describes the epidemiologic, clinical and pathologic profile of monoclonal gammopathies seen in the University Hospital of the West Indies (UHWI), a tertiary care referral centre. A retrospective analysis of 85 cases diagnosed at UHWI over the 5-year period 2003-2007 was conducted. The cases were identified from the bone marrow records as well as the computerized database of the Medical Records Department. Clinical presentation, family and personal history and demographic data were retrieved. Haematological and biochemical results were also analyzed. There were 85 patients diagnosed with monoclonal gammopathies. The M:F ratio was 1.2:1 and the mean age was 65.7±1.3 years. Eighty percent of the patients had skeletal pain and 40% experienced weight loss. Of the patients experiencing bone pain 56.7% had multiple lytic lesions, 26.7% had pathological fractures and 26.7% had compression fractures. Seventy-four patients (87.1%) had a haemoglobin level <12.0 g/dL with 52.9% having values <8.0 g/dL. Renal impairment was evident at diagnosis in 36.5% . Hypercalcemia was seen in 26.5% and hyperuricemia in 45.9%. Of the 79 patients who had serum protein electrophoresis performed, 77.2% had at least one monoclonal band and of these 24.6% had a monoclonal protein also present on urine protein electrophoresis. The demographic profile in this group of patients is largely similar to other studies in predominantly Caucasian populations; however there was a notable increase in prevalence of severe disease at presentation, with the majority of patients presenting at the most advanced stage. It is probable that these differences reflect socioeconomic factors and not merely inherent ethnic variation in disease biology.

Neuromuscular electrostimulation techniques: historical aspects and current possibilities in treatment of pain and muscle waisting

Application of electricity for pain treatment dates back to thousands of years BC. The Ancient Egyptians and later the Greeks and Romans recognized that electrical fishes are capable of generating electric shocks for relief of pain. In the 18th and 19th centuries these natural producers of electricity were replaced by man-made electrical devices. This happened in following phases. The first was the application of static electrical currents (called Franklinism), which was produced by a friction generator. Christian Kratzenstein was the first to apply it medically, followed shortly by Benjamin Franklin. The second phase was Galvanism. This method applied a direct electrical current to the skin by chemical means, applied a direct and pulsed electrical current to the skin. In the third phase the electrical current was induced intermittently and in alternate directions (called Faradism). The fourth stage was the use of high frequency currents (called d'Arsonvalisation). The 19th century was the "golden age" of electrotherapy. It was used for countless dental, neurological, psychiatric and gynecological disturbances. However, at beginning of the 20th century electrotherapy fell from grace. It was dismissed as lacking a scientific basis and being used also by quacks and charlatans for unserious aims. Furthermore, the development of effective analgesic drugs decreased the interest in electricity. In the second half of the 20th century electrotherapy underwent a revival. Based on animal experiments and clinical investigations, its neurophysiological mechanisms were elucidated in more details. The pain relieving action of electricity was explained in particular by two main mechanisms: first, segmental inhibition of pain signals to the brain in the dorsal horn of the spinal cord and second, activation of the descending inhibitory pathway with enhanced release of endogenous opioids and other neurochemical compounds (serotonin, noradrenaline, gamma aminobutyric acid (GABA), acetylcholine and adenosine). The modern electrotherapy of neuromusculo- skeletal pain is based in particular on the following types: transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation (PENS or electro-acupuncture) and spinal cord stimulation (SCS). In mild to moderate pain, TENS and PENS are effective methods, whereas SCS is very useful for therapy of refractory neuropathic or ischemic pain. In 2005, high tone external muscle stimulation (HTEMS) was introduced. In diabetic peripheral neuropathy, its analgesic action was more pronounced than TENS application. HTEMS appeared also to have value in the therapy of symptomatic peripheral neuropathy in end-stage renal disease (ESRD). Besides its pain-relieving effect, electrical stimulation is of major importance for prevention or treatment of muscle dysfunction and sarcopenia. In controlled clinical studies electrical myostimulation (EMS) has been shown to be effective against the sarcopenia of patients with chronic congestive heart disease, diabetes, chronic obstructive pulmonary disease and ESRD.

PKC412 (Midostaurin) Is Safe and Highly Effective in Systemic Mastocytosis Patients: The Bologna Experience

Abstract 1749 Introduction.Mastocytosis is a myeloid neoplasm characterized by abnormal accumulation and frequent activation of mast cells (MCs) in various organs, mostly bone marrow, skin, liver and gastrointestinal tract. In most adult patients, the systemic form of mastocytosis (SM) is diagnosed, which includes an indolent, an aggressive and a leukemic subvariant. The c-kit mutation D816V is detectable in most adult patients with SM. Treatment of SM usually focuses on symptom relief by histamine receptor antagonists and other supportive therapy. However, in aggressive and leukemic variants, cytoreductive and targeted drugs must be applied. Methods.From 2008, 11 patients (male/female=3/8) affected by Mastocytosis, have been referred to our Institution. The median age was 53 years. All the patients underwent a bone marrow biopsy, with flow citometry and molecular biology analysis, in order to identify the presence of D816V mutation of c-Kit gene. Serum tryptase level was tested, resulting elevated in all cases. According to 2008 WHO diagnostic criteria, 9 patients presented with SM, whereas in the other cases a skin isolated involvement was detected. Systemic symptoms were characterized by nausea, diarrhoea, asthenia, weight loss, pruritus and serotine fever, identifying an aggressive form of the disease in 5/11 patients, due to skeletal involvement in three cases, ascitis and liver function impairment in another one and bone marrow disfunction in the fifth one. Therefore, since a first line therapy with supportive care and histamine receptor antagonists wasn't followed by a significant benefit, a personalized use of PKC412 was asked and obtained for all these five patients. Results.From March 2011 three out of the five patients with aggressive SM have received a prolonged period of treatment with PKC412, which was administered orally, at the dosage of 100 mg twice daily, without rest periods. The drug was well tolerated. No serious adverse events were observed. All the patients obtained a quick and prolonged improvement of clinical symptoms, in terms of weight gain, bowel function and skeletal pain. At the bone marrow evaluation, the persistence of the D816V c-kit mutation was observed, despite a significant decrease of mast cell marrow involvement. In one case we observed, after a first good response, a disease progression, characterized by the sudden reoccurrence of the same symptoms detected at diagnosis, confirmed by a relevant expansion of a pathologic mast cell population in the bone marrow. After a rest period, the drug was readministered, and a second remission was obtained. Conclusions.PKC412 is safe and effective in patients with SM, being able to significantly improve not only the gastrointestinal and systemic symptoms, but also the haematological profile. The persistence of the D816V c-kit mutation, despite a morphologic remission, suggests that many other oncogenic factors may be responsible for the pathogenesis of the disease. Acknowledgments.Work supported by European LeukemiaNet, AIRC, AIL, PRIN, Fondazione del Monte di Bologna e Ravenna, University of Bologna. Disclosures:Baccarani:Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; PFIZER: Consultancy, Honoraria, Speakers Bureau; ARIAD: Consultancy, Honoraria, Speakers Bureau. Martinelli:NOVARTIS: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; PFIZER: Consultancy; ARIAD: Consultancy.

O10 Enzalutamide, an androgen receptor signaling inhibitor, improves overall survival, time to first skeletal related event and pain

O10 Enzalutamide, an androgen receptor signaling inhibitor, improves overall survival, time to first skeletal related event and pain

Impact of enzalutamide, an androgen receptor (AR) signalling inhibitor, on time to first skeletal related event (SRE) and pain in the phase 3 AFFIRM study

Impact of enzalutamide, an androgen receptor (AR) signalling inhibitor, on time to first skeletal related event (SRE) and pain in the phase 3 AFFIRM study

Frovatriptan

Frovatriptan (Migard®; Frova®) is an orally administered triptan approved for the acute treatment of adults with migraine, with or without aura. This article reviews the pharmacology of frovatriptan, focusing on its efficacy and tolerability. The precise mechanism of action of frovatriptan is unknown, but is thought to stem from agonism at serotonin 5-HT(1B) and 5-HT(1D) receptors, resulting in inhibition of intracranial and extracerebral artery vasodilation, along with possible anti-inflammatory and pain inhibiting effects. Frovatriptan appears to be functionally selective for 5-HT receptors in human basilar arteries over coronary arteries, which could translate into a low cardiovascular risk. In contrast to other triptans, frovatriptan has a long terminal elimination half-life in blood of ≈26 hours, which can be expected to be associated with a sustained treatment effect. Oral frovatriptan 2.5 mg was efficacious in patients with moderate to severe migraine attacks; in randomized, double-blind trials the proportion of patients with headache response at 2 hours (primary endpoint) was consistently significantly higher in frovatriptan than placebo groups. Frovatriptan was generally well tolerated in short-term clinical trials and when used over the longer term. The most frequent treatment-emergent adverse events occurring at a frequency ≥1% higher in frovatriptan than placebo recipients were dizziness, fatigue, headache, paraesthesia, flushing, skeletal pain, hot or cold sensation, dry mouth, chest pain and dyspepsia. In a study in patients with coronary artery disease, or who were at high risk of coronary artery disease, there was no increase over placebo in the occurrence of clinically significant ECG changes or in cardiac rhythm disturbances. In a further trial, frovatriptan administered early in a migraine attack was more efficacious than placebo followed by later administration of frovatriptan as pain progressed. Three crossover trials compared early administration of frovatriptan 2.5 mg with almotriptan 12.5 mg, rizatriptan 10 mg and zolmitriptan 2.5 mg in patients with migraine. There were no significant between-group differences in patient drug preference scores (primary endpoint) or in other endpoints, except for headache recurrence, which favoured frovatriptan in two of the trials. The trials did not test noninferiority of frovatriptan to the comparator. In a placebo-controlled trial that included a sumatriptan active treatment arm, sumatriptan 100 mg was significantly more efficacious than frovatriptan 2.5 mg for this primary endpoint. Frovatriptan was generally better tolerated than all four triptan comparators. In summary, frovatriptan was an efficacious acute treatment for moderate to severe migraine attacks and had a favourable tolerability profile, although in a single trial, it was not as efficacious as sumatriptan. Administration of frovatriptan early in an attack while the attack was at a mild level of intensity was more efficacious than late administration. Furthermore, in clinical trials adopting this early administration strategy, frovatriptan was not significantly less efficacious than almotriptan, rizatriptan and zolmitriptan, appeared to have a more sustained treatment effect, and was better tolerated than the comparators. Frovatriptan provides an alternative treatment for migraine, especially in patients who have had adverse events or frequent headache recurrences with triptans or other antimigraine drugs, and who are amenable to adopting an early administration strategy.

310 - Evaluation of Aromatase Inhibitor-Related Arthralgia in Early Breast Cancer Patients

ABSTRACT Introduction Aromatase inhibitors (AI) have demonstrated a disease-free survival benefit compared with tamoxifen as adjuvant therapy in the treatment of hormone-dependent early breast cancer in postmenopausal women. Although the AI are associated with fewer thromboembolic events and endometrial abnormalities than tamoxifen, an increase in arthralgia, skeletal, and muscle pain has been reported and cited as the primary reason for discontinuation of AI therapy. The aim of our study was to evaluate the incidence and the impact of the arthralgia syndrome in our population. Methods Postmenopausal patients with the diagnosis of early-stage hormone-sensitive breast cancer receiving AI therapy at our institution were included prospectively between 2010-2012. We performed a specific survey to evaluate articular toxicity collecting presence of arthralgias, EVA scale, use of analgesic, start time and localization of the pain. Clinical data was collected from our department database. Univariate analysis was used to compare those with AI-related arthralgia and different demographic and clinical features. Results A total of 83 women were included, with a mean age 63.2, BMI 28.4, menopause mean age 48.2. Regarding to the features of the primary tumor, 81.9% had ductal carcinoma histology, 28.9% stage I, 54.2% stage II, 16.8% stage III. At the moment of the evaluation, 68.7% (57/83) were receiving treatment with anastrozole, 15.7% (13/83) letrozole, 15.7% (13/83) exemestane. 86.7% (72/83) had joint pain, of them 68.1% (49/72) related their pain to the hormone therapy, 31.9% (23/72) to previous diseases or another treatments. The articulations more frequently affected were located in the back, knees and hands. Regarding to the pain intensity, mean maximum EVA was 6.03, minimum 1.06. Only 2 of the patients affected stopped therapy, and it was changed for another aromatase inhibitor. No differences were seen between the different aromatase inhibitors. Conclusions The incidence of arthralgia associated with aromatase inhibitors was superior in our series compared with results previously published in clinical trials. Further research in this field should be developed to clarify the prevalence and severity of joint symptoms related to AI and to define factors that may be associated with an increased risk of this treatment-related adverse effect. Disclosure All authors have declared no conflicts of interest.

Radionuklidtherapie bei Knochenmetastasen urologischer Tumoren: Eine vergessene Therapie?

Many patients suffering from urological or non-urological malignancies develop bone metastases. One symptom often found is severe skeletal pain which siginificantly lowers the quality of life. Further symptoms are pathological fractures, spinal cord compression and hypercalcemia. The systemic radiopharmaceutical therapy represents an important systemic treatment option, in addition to chemotherapy, hormone therapy, external beam radiation, bisphosphonates and analgesics. The radionuclide therapy is rarely used and often used in a later phase of disease, mainly known for the bone pain palliation. This review article should help remind physicians to use this interesting therapy. It focuses on the common radionuclides Strontium-89-chloride, Samarium-153-EDTMP (ethylene-diamine-tetra-methylene-phosphonate) and Rhenium-186-HEDP (hydroxyethylidene-diphosphonate), their physical characteristics and differences, contraindications of the therapy like spinal cord compression and side effects. Additionally, potential tumoricidal activity and improvement of survival are discussed when using the radionuclides repetitively or in combination. The European and German guidelines are included. Furthermore, the combination of radionuclides and bisphosphonates or chemotherapy are briefly discussed, based on available clinical studies. Additionally, alpharadin (radium-223 chloride) is discussed, an experimental radiopharmaceutical under clinical evaluation, which emits alpha-radiation. In phase III clinical trials, it was shown to significantly increase the median overall survival in patients with bone metastases from advanced prostate cancer.

Pain and gender differences: A clinical approach

IntroductionPain continues to be one of the most frequent complaints in clinical centers. Consequently, understanding gender differences in relation to pain is important and critical for the clinical management of patients by the different healthcare services. Pain in patients of different gender is usually treated in the same way; however, there are several gender-associated factors involved in the management of pain, which sometimes are not taken into consideration in clinical practice. ObjectiveTo describe the differences between men and women as far as pain is concerned, taking into consideration anatomical, physiological, neural, hormonal, psychological, social and cultural factors in the practice of anesthesia. MethodologyA non-systematic review was undertaken using the key words in the Pubmed/Medline, Science Direct, OVID, SciElo databases. Results and conclusionsDifferences between men and women when it comes to pain involve anatomical, physiological, neural, hormonal, psychological, social and cultural factors. When examining those factors, it is found that women report pain more frequently, and have a lower threshold for pain than men. They usually complain more of muscle–skeletal, neuropathic, electrical shock and temperature-related pain, but respond better to opioids, in particular κ receptor-binding opioids.