Methods.— Throughout all regions of China, 5041 non-related adult respondents aged 18-65 years were randomly sampled from the general population according to the expanded programme on immunization method FK506 concentration established by World Health Organization. They were visited by door-to-door calling and surveyed using the structured questionnaire developed by Lifting The Burden, translated into Chinese and adapted to Chinese culture after a pilot study. Results.—

The responder rate was 94.1%. The estimated 1-year prevalence of primary headache disorders was 23.8% (95% confidence interval 22.6-25.0%), of migraine 9.3% (95% confidence interval 8.5-10.1%), of tension-type headache (TTH) 10.8% (9.9-11.6%), and of chronic

daily headache (CDH) 1.0% (0.7-1.2%). Of respondents with migraine, TTH, and CDH, moderate or severe impact and therefore high need for effective medical care were reported by 38.0%, 23.1%, and 47.9%, respectively. CP-673451 datasheet The World Health Organization quality of life-8 questionnaire showed that all 3 types of headache reduced life quality. The total estimated annual cost of primary headache disorders, including migraine, TTH, and CDH was CNY 672.7 billion, accounting for 2.24% of gross domestic product (GDP) (direct cost: CNY 108.8 billion, 0.36% of GDP; indirect cost: CNY 563.9 billion, 1.88% of GDP). Conclusion.— The prevalence of primary headaches is high in China and not dissimilar from the world average. These headaches cause disability, impair work, study and daily activities, decrease life quality, and bring about a heavy and hitherto

unrecognized socioeconomic burden. “
“Objective.— This study evaluated the effectiveness of a single fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan–naproxen) using a very early treatment paradigm in migraine patients whose attacks were historically accompanied by cutaneous allodynia. Background.— Evidence suggests that allodynic migraineurs may demonstrate a better response when treated prior to developing central sensitization, and that these patients are treated medchemexpress more effectively with a compound of sumatriptan and naproxen sodium than either drug alone. This study targeted patients who have accompanying allodynia using a very early treatment paradigm where treatment was initiated while symptoms were still mild. Methods.— This was an open-label prospective, outpatient study of adult migraineurs who had screened positive for cutaneous allodynia and typically experienced moderate to severe pain preceded by an identifiable mild pain phase. Patients were treated with sumatriptan–naproxen using a very early intervention paradigm in 4 test migraines over 12 weeks where dosage occurred within 30 minutes of symptom onset.

244-246 Finally, enhancing mtFAO in liver can also alleviate IR, which could be dependent or not on the reduction in hepatic lipids.247,248 Obese patients are consuming on average

more drugs than nonobese individuals.249 However, numerous drugs can impair mitochondrial function, or more broadly, lipid homeostasis.12,17,250 Excessive alcohol consumption is also able to impair mitochondrial function and lipid homeostasis.12,17,251 Thus, NAFLD could worsen during the prolonged exposure of such xenobiotics. Using rodent models with preexisting hepatic steatosis and/or NASH, an aggravation of liver lesions was observed with phenobarbital, rosiglitazone, and pentoxifylline.17,252 In addition, clinical studies suggested that NASH could be induced, or aggravated, in obese individuals treated with drugs such as tamoxifen, methotrexate, irinotecan, Ibrutinib in vitro and nucleoside reverse

transcriptase inhibitors (NRTIs) such as stavudine and didanosine.17,253,254 NAFLD aggravation was also shown in rodents with ethanol,54,255 and in ducks force-fed with corn contaminated with mycotoxins.256 Obese individuals with NAFLD could also be more prone to develop drug-induced acute hepatitis. Nutlin-3a cost This has been suggested for halothane and acetaminophen.17,254 For these drugs, which undergo CYP2E1-mediated biotransformation into highly toxic metabolites, increased liver injury could be secondary to CYP2E1 induction.39,254,257 Underlying mitochondrial dysfunction could also lead to MCE公司 higher susceptibility to drug-induced acute hepatitis, although further investigations are needed to confirm this hypothesis. Although studies dealing with mitochondrial dysfunctions in NAFLD present some discrepancies, a frequent finding is the significant alteration of MRC activity in NASH. Importantly, moderate impairment of MRC activity can already be observed in simple fatty liver. Hence, MRC activity could progressively decline during the progression of NAFLD. In contrast, mtFAO is stimulated (or at least preserved) in fatty liver and NASH, most probably

as a compensatory mechanism in order to restrain fat accumulation. This imbalance between mtFAO and MRC is leading to ROS overproduction by way of enhanced leakage of electrons from the MRC.5,7,17,63,171 It is likely that this event triggers a vicious cycle since mitochondrial ROS are able to oxidatively damage nearby MRC enzymes and mtDNA. If this scheme is correct, restoring MRC activity in NAFLD could be a major goal to achieve in order to alleviate oxidative stress. Since mitochondrial ROS could play a significant role in cell death, inflammation, and fibrosis,258-260 developing drugs improving both mtFAO and MRC activity could provide major benefits beyond the improvement of fatty liver.

16 VhlF/F, VhlF/FHif-1αF/F, and VhlF/FHif-2αF/F were previously described.16 For temporal hepatocyte-specific disruption, VhlF/F, VhlF/FHif-1αF/F, and VhlF/FHif-2αF/F mice were crossed with mice harboring the Cre-ERT2 recombinase under control of the albumin promoter, SA-Cre-ERT2.17 The mice are a mixed Sv129 and C57BL/6 background, and wild-type littermate control mice were used as a comparison for each experiment. Mice were used between the ages of 6 and 8 weeks for all experiments. For activation of the SA-Cre-ERT2 recombinase for short-term experiments (i.e., 1 and 3 days), mice were treated with

1 dose of tamoxifen (2 mg/mouse in corn oil) by intraperitoneal (IP) injection and killed 24 hours or 3 GSK2118436 clinical trial days after tamoxifen treatment. For the 7-day and 2-week experiments, mice were fed tamoxifen in the diet for 2 days, then replaced with regular chow and killed at 7 days or 2 weeks after initial tamoxifen administration. For the alcohol treatment, mice were treated Palbociclib with tamoxifen by IP injection on 2 consecutive days, then were fed, ad libitum, a 4% alcohol-containing liquid diet (Lieber-DeCarli Diet; Dyets, Inc., Bethlehem, PA) and killed 2 weeks after alcohol administration. Mice were housed in temperature- and light-controlled rooms and were given water and pelleted chow ad libitum. All animal studies were carried out in accordance with guidelines

and approved by the National Cancer Institute and University of Michigan Animal Care and Use Committee. RNA was extracted from tissues, reverse transcribed, and quantitative 上海皓元 real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) was performed using primer sequences listed in Supporting Table 1. Liver whole-cell or nuclear extracts

were prepared. Membranes were incubated with antibodies against HIF-1α, HIF-2α (Novus Biologicals, Littleton, CO), ANGPTL3 (Santa Cruz Biotechnology, Inc., Santa Cruz, CA), and smooth muscle actin (SMA) (Sigma, St. Louis, MO), phophorylated, and total acetyl-CoA carboxylase (ACC) (Cell Signaling Technology, Beverly, MA) signals obtained were normalized to GAPDH (Santa Cruz) for whole cell extract and histone H1 (Santa Cruz), pregnane X receptor (PXR), and hepatic nuclear factor 4 (HNF-4α) (Abcam, Cambridge, MA) for nuclear extracts. Liver cDNAs were hybridized to an Agilent 44 K mouse 60-peptide oligomer microarray (Agilent Technologies, Santa Clara, CA). Data were processed and analyzed by a Genespring GX software package (Agilent Technologies). Hematoxylin and eosin (H&E) and Masson’s trichrome staining were performed on formalin fixed paraffin embedded sections. Oil red O staining was performed on frozen liver sections or adherent hepatoma-derived Hepa-1 cells. For quantification of oil red O in Hepa-1 cells, isopropanol was added to the cells after staining. Absorbance was measured at 510 nm in the isopropanol extracts, and values were normalized to protein content.

16 VhlF/F, VhlF/FHif-1αF/F, and VhlF/FHif-2αF/F were previously described.16 For temporal hepatocyte-specific disruption, VhlF/F, VhlF/FHif-1αF/F, and VhlF/FHif-2αF/F mice were crossed with mice harboring the Cre-ERT2 recombinase under control of the albumin promoter, SA-Cre-ERT2.17 The mice are a mixed Sv129 and C57BL/6 background, and wild-type littermate control mice were used as a comparison for each experiment. Mice were used between the ages of 6 and 8 weeks for all experiments. For activation of the SA-Cre-ERT2 recombinase for short-term experiments (i.e., 1 and 3 days), mice were treated with

1 dose of tamoxifen (2 mg/mouse in corn oil) by intraperitoneal (IP) injection and killed 24 hours or 3 p38 MAPK inhibitor days after tamoxifen treatment. For the 7-day and 2-week experiments, mice were fed tamoxifen in the diet for 2 days, then replaced with regular chow and killed at 7 days or 2 weeks after initial tamoxifen administration. For the alcohol treatment, mice were treated selleckchem with tamoxifen by IP injection on 2 consecutive days, then were fed, ad libitum, a 4% alcohol-containing liquid diet (Lieber-DeCarli Diet; Dyets, Inc., Bethlehem, PA) and killed 2 weeks after alcohol administration. Mice were housed in temperature- and light-controlled rooms and were given water and pelleted chow ad libitum. All animal studies were carried out in accordance with guidelines

and approved by the National Cancer Institute and University of Michigan Animal Care and Use Committee. RNA was extracted from tissues, reverse transcribed, and quantitative MCE公司 real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) was performed using primer sequences listed in Supporting Table 1. Liver whole-cell or nuclear extracts

were prepared. Membranes were incubated with antibodies against HIF-1α, HIF-2α (Novus Biologicals, Littleton, CO), ANGPTL3 (Santa Cruz Biotechnology, Inc., Santa Cruz, CA), and smooth muscle actin (SMA) (Sigma, St. Louis, MO), phophorylated, and total acetyl-CoA carboxylase (ACC) (Cell Signaling Technology, Beverly, MA) signals obtained were normalized to GAPDH (Santa Cruz) for whole cell extract and histone H1 (Santa Cruz), pregnane X receptor (PXR), and hepatic nuclear factor 4 (HNF-4α) (Abcam, Cambridge, MA) for nuclear extracts. Liver cDNAs were hybridized to an Agilent 44 K mouse 60-peptide oligomer microarray (Agilent Technologies, Santa Clara, CA). Data were processed and analyzed by a Genespring GX software package (Agilent Technologies). Hematoxylin and eosin (H&E) and Masson’s trichrome staining were performed on formalin fixed paraffin embedded sections. Oil red O staining was performed on frozen liver sections or adherent hepatoma-derived Hepa-1 cells. For quantification of oil red O in Hepa-1 cells, isopropanol was added to the cells after staining. Absorbance was measured at 510 nm in the isopropanol extracts, and values were normalized to protein content.

The conserved site changes occurred in the absence of virological breakthrough at the following loci: rtR51K; rtL101F/L; and rtV173L, rtL180M, and rtM204V PD-0332991 cell line (Fig. 1A-C). Clonal analysis of the baseline sample from the lamivudine-naive patient with lamivudine resistance mutations demonstrated the presence of the rtV173L, rtL180M, and rtM204V mutational pattern at a frequency of 6.5% with

individual mutations present in up to 15% of the clones. Phenotypic analysis of the baseline and post-baseline isolates was performed for the three patients with post-baseline conserved site changes. Because the rtL101 change was observed as a mixture, a clone containing the full rtL101F change was also phenotyped to evaluate the impact of this substitution. The pHY92 laboratory strain and the

laboratory isolate containing the rtA181V and rtN236T ADV-associated mutations were used as controls for tenofovir sensitivity and reduced susceptibility, respectively. Overall, there was no change in tenofovir susceptibility within the three patients who developed conserved site changes in the pol/RT (Table 2). Among the 215 patients originally randomized to the ADV arms of the studies, 196 entered the OL-TDF phase. Nineteen of the 196 patients (9.7%) remained viremic after up to 96 weeks of OL-TDF; 1 discontinued TDF monotherapy at week 80, 14 patients added FTC to TDF between study weeks 72 and 120 (median time of TDF monotherapy = 30 weeks), 上海皓元 and 4 patients received 96 weeks of TDF monotherapy. The majority of the patients (11/19, 58%) showed no change in the pol/RT learn more versus the week 48 results (the last on-ADV results), 4 of 19 (21%) harbored polymorphic site changes, and 3 of 19 (16%) harbored distinct conserved site changes; PCR amplification failed for 1 patient (Table 1). The conserved site changes occurred at the following loci: rtG152E; rtA307A/T; and rtN236N/T and rtR274R/Q. Only

rtG152E was observed in the context of confirmed virological breakthrough (Fig. 1D-F). Phenotypic evaluations of a site-directed mutant containing the rtG152E substitution demonstrated that the virus remained susceptible to inhibition by tenofovir in vitro (Table 2), and the corresponding patient achieved undetectable HBV DNA levels with continued TDF monotherapy (Fig. 1D). Repeated attempts to obtain phenotypic results from either the patient pool or a clone containing the rtA307T substitution were unsuccessful, and the substitution was not observed upon subsequent genotypic testing. For patient 017, because the conserved site changes at rtN236 and rtR274 were observed as mixtures, individual clones containing the full changes were phenotyped. Phenotypic analysis of the viral pool remained sensitive to inhibition by tenofovir, as did a clone containing the single rtR274Q substitution.

The conserved site changes occurred in the absence of virological breakthrough at the following loci: rtR51K; rtL101F/L; and rtV173L, rtL180M, and rtM204V Quizartinib mouse (Fig. 1A-C). Clonal analysis of the baseline sample from the lamivudine-naive patient with lamivudine resistance mutations demonstrated the presence of the rtV173L, rtL180M, and rtM204V mutational pattern at a frequency of 6.5% with

individual mutations present in up to 15% of the clones. Phenotypic analysis of the baseline and post-baseline isolates was performed for the three patients with post-baseline conserved site changes. Because the rtL101 change was observed as a mixture, a clone containing the full rtL101F change was also phenotyped to evaluate the impact of this substitution. The pHY92 laboratory strain and the

laboratory isolate containing the rtA181V and rtN236T ADV-associated mutations were used as controls for tenofovir sensitivity and reduced susceptibility, respectively. Overall, there was no change in tenofovir susceptibility within the three patients who developed conserved site changes in the pol/RT (Table 2). Among the 215 patients originally randomized to the ADV arms of the studies, 196 entered the OL-TDF phase. Nineteen of the 196 patients (9.7%) remained viremic after up to 96 weeks of OL-TDF; 1 discontinued TDF monotherapy at week 80, 14 patients added FTC to TDF between study weeks 72 and 120 (median time of TDF monotherapy = 30 weeks), MCE and 4 patients received 96 weeks of TDF monotherapy. The majority of the patients (11/19, 58%) showed no change in the pol/RT buy Carfilzomib versus the week 48 results (the last on-ADV results), 4 of 19 (21%) harbored polymorphic site changes, and 3 of 19 (16%) harbored distinct conserved site changes; PCR amplification failed for 1 patient (Table 1). The conserved site changes occurred at the following loci: rtG152E; rtA307A/T; and rtN236N/T and rtR274R/Q. Only

rtG152E was observed in the context of confirmed virological breakthrough (Fig. 1D-F). Phenotypic evaluations of a site-directed mutant containing the rtG152E substitution demonstrated that the virus remained susceptible to inhibition by tenofovir in vitro (Table 2), and the corresponding patient achieved undetectable HBV DNA levels with continued TDF monotherapy (Fig. 1D). Repeated attempts to obtain phenotypic results from either the patient pool or a clone containing the rtA307T substitution were unsuccessful, and the substitution was not observed upon subsequent genotypic testing. For patient 017, because the conserved site changes at rtN236 and rtR274 were observed as mixtures, individual clones containing the full changes were phenotyped. Phenotypic analysis of the viral pool remained sensitive to inhibition by tenofovir, as did a clone containing the single rtR274Q substitution.

24 Since dKO mice displayed impaired liver damage

and fibrosis, we analyzed whether RAGE ablation affects OC activation. Liver sections Temozolomide supplier of 3- and 6-month-old control, Mdr2−/−, and dKO mice were stained for the OC markers A6 (Fig. 3D) and pan-CK (Supporting Fig. 6).31–33 Positive staining in control liver sections was restricted to the portal tracts, whereas intense staining for activated OC invading the liver parenchyma was found in 3- and 6-month-old Mdr2−/− livers. Importantly, OC activation was strongly impaired in dKO liver sections. These data demonstrate an obvious delay in the onset of liver damage and in OC activation in the premalignant phase of dKO mice. On the contrary, premalignant WT and Rage−/− mice 6 months after DEN injection revealed neither increased ALT levels nor enhanced fibrosis or OC activation when compared to age-matched untreated WT and Rage−/− mice (Supporting Fig. Adriamycin cell line 3A-C and data not shown). To define more precisely the role played by RAGE on OC activation, we analyzed RAGE expression in hepatocytes, leukocytes (CD45-positive), and OC isolated from livers of mice fed with a CDE diet, a regime which induces liver injury with a prominent OC reaction.27, 34 qPCR and western

blot analyses revealed that RAGE was significantly expressed in inflammatory cells but barely detectable in hepatocytes. Noteworthy, OC showed the highest RAGE transcript levels and RAGE protein was easily detectable (Fig. 4A,B), supporting the assumption that RAGE represents a direct regulator of OC activation. To confirm this hypothesis, we interfered with RAGE signaling in WT mice, in which an OC response

was promoted by a 3-week CDE regime. After the first week of treatment, mice were injected every second day with soluble RAGE (sRAGE, 100 μg/mouse), a RAGE decoy receptor,35 or saline. After 2 weeks of treatment mice were sacrificed and livers were analyzed. Quantification of serum ALT levels and PCNA immunohistochemistry revealed increased liver damage and compensatory proliferation in CDE-treated mice as compared to normal diet controls, which was not affected by the administration of sRAGE (Fig. 5A; 上海皓元医药股份有限公司 Supporting Fig. 7A), confirming that sRAGE treatment had no major impact on CDE-induced tissue damage. In line with our previous data, staining for A6 and pan-CK revealed impaired OC activation on liver sections of CDE-sRAGE as compared to CDE-saline animals (Fig. 5B; Supporting Fig. 8A). An impaired OC activation was also observed in Rage−/− mice as compared to CDE-treated WT mice fed a CDE diet for 4 weeks (Supporting Fig. 8B). However, we could observe neither an increase in apoptosis nor an evident infiltration of CD45-positive cells or fibrotic phenotype in either NaCl- or sRAGE-treated mice fed a CDE or a normal diet (Supporting Fig. 7B-D), supporting the assumption that RAGE-dependent OC activation is independent of RAGE signaling in the activation and/or recruitment of immune cells.

12 Given that the mechanisms by which Alms1 Vadimezan ic50 mutations cause the phenotypes of Alström disease are incompletely understood at best, it is premature at this time to state that the results with the foz/foz mice are not unique to this mutation, but rather generally applicable to NAFLD. In their defense, the authors are careful to point

this out and couch their results accordingly. In conclusion, this work clearly supports the concept that cholesterol could, in principle, be a hepatotoxic culprit in NAFLD/NASH. Previous work by others has shown that dietary FC loading depletes hepatic mitochondrial glutathione and sensitizes the liver to cell killing via tumor necrosis factor-α or Fas signaling.15 Such a mechanism is in line with the observation in the current work that indices of apoptosis (cytokeratin-18) were dramatically higher in the foz/foz mice fed HFD with cholesterol (see Fig. 6A in van Rooyen DM et al.10). Whether these results translate generally to fatty liver diseases remains to be seen. However, even Selleck Fulvestrant in the case that these results do not, the finding that foz/foz mice are relatively normal when restricted to a low-fat diet may at least be useful information for the management of the metabolic disorder of Alström disease. “
“The main methods of treatment

for hepatocellular carcinoma (HCC) in Japan are hepatic resection, radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Meticulous follow up is then undertaken to check for recurrence, which is treated using repeated RFA or TACE. Hepatic arterial infusion chemotherapy has been introduced as treatment for advanced HCC, and the molecular-targeted

drug MCE公司 sorafenib is also now available. Rigorous medical care using these treatment methods and early diagnosis mean that the prognosis for HCC in Japan is the best in the world. This paper reviews the treatment strategies for HCC in Japan. TREATMENT FOR HEPATOCELLULAR carcinoma (HCC) is peculiar in that, unlike other solid carcinomas, the treatment methods must be selected in consideration of the underlying clinical condition of the liver. A wide range of treatment methods is available, including hepatectomy, liver transplant, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), sorafenib therapy, hepatic arterial infusion chemotherapy (HAIC) and radiotherapy. These treatment methods can also be used in combination. This paper reviews the treatment strategies for HCC in Japan. MANY CASES OF HCC arise from liver cirrhosis, and are associated with deterioration in liver function. This means that in addition to cancer stage, hepatic reserve is also an important prognostic factor. This balance must be taken into account when choosing between different types of treatment.

12 Given that the mechanisms by which Alms1 FK506 mw mutations cause the phenotypes of Alström disease are incompletely understood at best, it is premature at this time to state that the results with the foz/foz mice are not unique to this mutation, but rather generally applicable to NAFLD. In their defense, the authors are careful to point

this out and couch their results accordingly. In conclusion, this work clearly supports the concept that cholesterol could, in principle, be a hepatotoxic culprit in NAFLD/NASH. Previous work by others has shown that dietary FC loading depletes hepatic mitochondrial glutathione and sensitizes the liver to cell killing via tumor necrosis factor-α or Fas signaling.15 Such a mechanism is in line with the observation in the current work that indices of apoptosis (cytokeratin-18) were dramatically higher in the foz/foz mice fed HFD with cholesterol (see Fig. 6A in van Rooyen DM et al.10). Whether these results translate generally to fatty liver diseases remains to be seen. However, even LY294002 in the case that these results do not, the finding that foz/foz mice are relatively normal when restricted to a low-fat diet may at least be useful information for the management of the metabolic disorder of Alström disease. “
“The main methods of treatment

for hepatocellular carcinoma (HCC) in Japan are hepatic resection, radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Meticulous follow up is then undertaken to check for recurrence, which is treated using repeated RFA or TACE. Hepatic arterial infusion chemotherapy has been introduced as treatment for advanced HCC, and the molecular-targeted

drug MCE sorafenib is also now available. Rigorous medical care using these treatment methods and early diagnosis mean that the prognosis for HCC in Japan is the best in the world. This paper reviews the treatment strategies for HCC in Japan. TREATMENT FOR HEPATOCELLULAR carcinoma (HCC) is peculiar in that, unlike other solid carcinomas, the treatment methods must be selected in consideration of the underlying clinical condition of the liver. A wide range of treatment methods is available, including hepatectomy, liver transplant, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), sorafenib therapy, hepatic arterial infusion chemotherapy (HAIC) and radiotherapy. These treatment methods can also be used in combination. This paper reviews the treatment strategies for HCC in Japan. MANY CASES OF HCC arise from liver cirrhosis, and are associated with deterioration in liver function. This means that in addition to cancer stage, hepatic reserve is also an important prognostic factor. This balance must be taken into account when choosing between different types of treatment.

Results.— A total of 1348 migraineurs (88% women) were included in this study (mean age 41 years). Based on physician diagnosis or validated criteria, 31% had IBS, 16% had CFS, and 10% had FM. Diagnosis of IC was reported by 6.5%, arthritis by 25%, and in women, endometriosis was reported by 15% and uterine fibroids

by 14%. At least 1 comorbid pain condition was reported by 61%, 2 conditions by 18%, and 3 or more by 13%. Childhood maltreatment was reported by 58% of the patients. Emotional abuse was associated AG-014699 molecular weight with increased prevalence of IBS, CFS, arthritis, and physical neglect with arthritis. In women, physical abuse was associated with endometriosis and physical neglect with uterine fibroids. Emotional abuse, and physical abuse and neglect (P < .0001 for all) were also associated with increased total number of comorbid conditions. In ordinal logistic regression models, adjusted for sociodemographics and current depression (prevalence 28%) and anxiety (prevalence 56%), emotional abuse (odds ratios [OR] = 1.69, 95% confidence intervals [CI]: 1.224-2.33) and physical neglect (OR = 1.73, 95% CI: 1.22-2.46) were

independently associated with an increased number Metabolism inhibitor of pain conditions. The cohort of women, similarly, had associations of emotional abuse (OR = 1.94, 95% CI: 1.40-2.72) and physical neglect (OR = 1.90, 95% CI: 1.34-2.68) with an increased number of pain comorbidities. Conclusion.— The association of childhood maltreatment and pain was stronger in those reporting multiple pain conditions and multiple maltreatment types. This finding suggests that in migraineurs childhood maltreatment may be a

risk factor for development of comorbid pain disorders. Childhood maltreatment is prevalent, particularly in clinic populations, and has been associated with a wide range of adult psychiatric and physical disorders.1-5 Many studies have focused on the relationship of abuse with depression and anxiety, 2 conditions strongly associated with painful conditions,6 including migraine.7 Although there are scant data on migraine per se, both population- and clinic-based studies have demonstrated an association of childhood abuse and recurrent headache.8-11 However, MCE公司 the relationship of childhood maltreatment and chronic pain conditions remains a subject of considerable debate.1,12,13 In our earlier multicenter clinic survey of women with migraine, those with a history of childhood abuse reported more severe headaches, more depression, and more somatic symptoms.14 Many of the somatic symptoms were pain-related (limb, joints, abdominal, headache, back, chest, and genital) and some symptom combinations suggested common syndromatic disorders (irritable bowel, chronic fatigue, and fibromyalgia [FM]) that are recognized as comorbid with migraine.15 We found the abuse-somatic symptom association was stronger in the cohort with major depression, yet depression did not fully mediate the relationship.