Antioxidants Supplementation in Acute Amitriptyline Abuse for Pain.

The fundamental aim of this study is to establish the role of antioxidant supplementation in alleviating acute amitriptyline induced oxidative stress. The effect of supplementation was compared on treatment of acute amitriptyline intoxication cases for pain management, with alpha lipoic acid (ALA) alone or with vitamin C, with that of healthy individuals (group I), and those receiving only routine standard treatment (RST) as control (group II). A total of 132 human subjects divided into 5 groups were supplemented with either placebo, RST, RST with vitamin C, RST with ALA, or RST with vitamin C, and ALA. Results of this study revealed that the decrease in the level of oxidative stress and enzyme activity was observed among those supplemented with either alpha lipoic acid alone or along with vitamin C, with a slightly more decrease in the latter group. P value of < 0.001 was considered statistically significant. The percentage of benefit of treatment on supplementation with vitamin C and alpha lipoic acid showed a marked increase in group V cases after supplementation with both in combination. The results provided that the oxidative stress induced by acute amitriptyline poisoning is comparatively decreased by supplementation with antioxidants like alpha lipoic acid and vitamin C, than those only on routine standard treatment.

Increased Levels of Omega-3 Fatty Acids and DHA Are Linked to Pain Reduction in Rheumatoid Arthritis Patients Treated with Janus Kinase Inhibitors.

Although Janus kinase inhibitors (JAKi) could reduce patient-reported pain in rheumatoid arthritis (RA), their mechanism remains unclear. Therefore, we examined lipid metabolites change in JAKi-treated patients and evaluate their association with pain reduction. We used 1H-NMR-based lipid/metabolomics to determine serum levels of lipid metabolites at baseline and week 24 of treatment. Serum levels of significant lipid metabolites were replicated by ELISA in 24 JAKi-treated and 12 tocilizumab-treated patients. Pain was evaluated with patients' assessment on a 0-100 mm VAS, and disease activity assessed using DAS28. JAKi or tocilizumab therapy significantly reduced disease activity. Acceptable pain (VAS pain ≤20) at week 24 was observed in 66.7% of JAKi-treated patients, and pain decrement was greater than tocilizumab-treated patients (ΔVAS pain 70.0 vs. 52.5, p = 0.0595). Levels of omega-3 fatty acids and docosahexaenoic acid (DHA) were increased in JAKi-treated patients (median 0.55 mmol/L versus 0.71 mmol/L, p = 0.0005; 0.29 mmol/L versus 0.35 mmol/L, p = 0.0004; respectively), which were not observed in tocilizumab-treated patients. ELISA results showed increased DHA levels in JAKi-treated patients with acceptable pain (44.30 µg/mL versus 45.61 µg/mL, p = 0.028). A significant association of pain decrement with DHA change, not with DAS28 change, was seen in JAKi-treated patients. The pain reduction effect of JAKi probably links to increased levels of omega-3 fatty acids and DHA.

Vitamin D Levels in Patients Presenting with Non-Specific Neuromuscular Pain and Fatigue in Ethiopia.

BACKGROUND: Vitamin D is an important micronutrient impacting multiple physiologic functions including calcium, phosphorus and bone metabolism. Various studies demonstrate low vitamin D levels in non-specific neuromuscular pain disorders and chronic-fatigue-syndromes. This observation was supported by significant improvement of these disorders following Vitamin D supplementation. Several studies demonstrate low serum vitamin D levels in healthy adult Ethiopians despite availability of abundant sunlight. METHOD: Retrospective medical records review of 62 patients presented to Yehuleshet Specialty Clinic between March 2014-August 2015 with non-specific neuromuscular pain and fatigue. Serum vitamin D levels were obtained at initial clinic visit. RESULTS: The mean (±SD) age was 51.5 ±15.5 years. Two-third (69.4%) of the participants were female. The majority (56.5%) presented with mixed symptoms, including generalized body ache, paresthesia, neck and back pain, while 45.2% reported fatigue. Fifteen (24.2%) participants were on antiepileptic drugs. All patients had initial serum vitamin D levels < 30 ng/ml, among these 62.9% demonstrated severe deficiency (< 12 ng/ml). Thirty (48.4%) participants reported symptomatic improvement after treatment with standard doses of vitamin D and calcium. Age > 50 years, being housewife, use of antiepileptic medications (AEDs), and higher serum parathyroid hormone are associated with severe vitamin D deficiency. CONCLUSION: This study demonstrated high prevalence of vitamin D deficiency among patients with non-specific neuromuscular pain and fatigue. Vitamin D replacement resulted in significant clinical improvement. It is important to screen vitamin D in individuals with limited sunlight exposure and patients on AEDs when presenting with neuromuscular pain and fatigue.

Analgesic action of Rubimaillin in vitro and in vivo.

Pain, a common symptom in clinics, is a serious impediment to quality of life. The analgesic drugs presently in use have poor efficacy, and are associated with undesirable side effects. Rubimaillin (Rub) is a naphthoquinone compound extracted from Chinese herbal medicine, and it has various biological activities. In this study, the analgesic effect of Rub, and its mechanism of action were investigated using glacial acetic acid-induced mice writhing model and a mice model of neurogenic and inflammatory bipolar pain. Analgesic effects were measured in different experimental groups. In vitro, RAW 264.7 cells were used to investigate the release of nitric oxide (NO), iNOS and COX-2 protein in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The results revealed that Rub reduced the number of acetic acid-induced writhing in mice, inhibited formalin-induced biphasic pain response, and suppressed the production of NO in RAW 264.7 cells. The mechanisms involved in the analgesic and anti-inflammatory effects of rub may be related to the inhibition of cyclooxygenase-2 (COX-2), endogenous inflammatory mediators, and reduction in the content of pain-induced mediators.

Omega-3 derivatives, specialized pro-resolving mediators: Promising therapeutic tools for the treatment of pain in chronic liver disease.

The main causes of liver injury are associated with inflammation and permanent damage. They can cause chronic liver disease (CLD), which is mainly related to viral hepatitis, alcohol consumption and non-alcoholic steatohepatitis, leading to fibrosis, cirrhosis and hepatocellular carcinoma. These conditions prevent the liver from working normally and make it begin to fail, which in turn may prompt a liver transplant. CLD and cirrhosis are the eleventh cause of death worldwide. At present, there are no approved pharmacological treatments to prevent, treat or resolve liver fibrosis. The prevalence of pain in the hepatic disease is elevated with ranges between 30% and 40%. Most of the pain drugs require hepatic function; therefore, the suitable control of pain is still a clinical challenge. Specialized pro-resolving mediators (SPM): lipoxins, resolvins, protectins and maresins, are potent endogenous molecules (nM concentrations) that modulate inflammatory body responses by reducing neutrophil infiltration, macrophage activity and pain sensitization. SPM have anti-inflammatory properties, stimulate tissue resolution, repair and regeneration, and exhibit anti-nociceptive actions. Furthermore, SPM were tried on different cellular, animal models and human observational data of liver injury, improving the pathogenesis of inflammation and fibrosis. In the present work, we will describe recent evidence that suggests that SPM can be used as a therapeutic option for CLD. Additionally, we will examine the role of SPM in the control of pain in pathologies associated with liver injury.

Effects of an Extract of Salmon Milt on Symptoms and Serum TNF and Substance P in Patients With Fibromyalgia Syndrome.

PURPOSE: The aim of this study was to evaluate the effects of a dietary supplement containing primarily an extract of salmon's milt (semen) on symptoms and blood levels of proinflammatory molecules in patients with fibromyalgia syndrome (FMS), a chronic, painful musculoskeletal disease without a distinct pathogenesis or treatment. We recently reported increased serum levels of the proinflammatory molecules substance P (SP) and tumor necrosis factor (TNF) in patients with FMS as compared to those in normal controls. METHODS: This prospective, open-label study was conducted in patients with FMS (n = 87; 80 women, 7 men; age range, 18-80 years) selected from 2 clinical centers in Spain. Patients were administered the supplement and were evaluated at weeks 1 (before treatment), 4, 8, and 12 (end of treatment) for clinical parameters of functioning, fatigue, and pain, as well as overall impression. Patients were directed to take 1 capsule per day in the morning for the first 4 weeks, followed by 1 capsule in the morning and 1 capsule in the evening for the remaining 8 weeks. Differences in symptom scores in patients with FMS between weeks 1 and weeks 4, 8, and 12 were evaluated using ANOVA. Blood was obtained and serum separated in patients with FMS at 1 and 12 weeks and in a separate population of healthy controls (n = 20; 15 women, 5 men; age range, 25-65 years). Serum levels of SP and TNF were measured in patients with FMS at 1 and 12 weeks and in healthy controls by ELISA. TNF and SP levels in patients with FMS were compared between weeks 1 and 12, as well as between patients with FMS and untreated controls, using the Mann-Whitney U test. FINDINGS: Clinical parameters of functioning, fatigue, and pain, as well as overall impression, were improved significantly at 4 weeks as compared to 1 week and remained unchanged for the duration of the study (all, P < 0.0001). Serum TNF and SP levels were significantly elevated at 1 week in patients with FMS compared to controls and were decreased significantly at 12 weeks as compared to 1 week (all, P < 0.0001). IMPLICATIONS: Our findings indicate that this dietary supplement may significantly improve symptoms in patients with FMS. This is the first time to our knowledge that any molecule has been reported to be associated with a reduction in serum SP level. Consequently, the supplement or its hypothesized main active ingredient, spermine, may be developed as a novel treatment approach to FMS or other neuroinflammatory conditions. ClinicalTrials.gov identifier: NCT03911882.

Anti-inflammatory and antinociceptive activities of glucagon-like peptides: evaluation of their actions on serotonergic, nitrergic, and opioidergic systems.

RATIONALE: Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are gut derived hormones. GLP-1 and GLP-2 were shown to have pleiotropic effects in intestinal and pancreatic diseases. OBJECTIVE: We aimed to investigate the activities of GLP-1 and GLP-2 on nociception and inflammation in mice, involving their actions on serotonergic, nitrergic, and opioidergic systems. METHODS: Antinociceptive and anti-inflammatory activities of intraperitoneally injected GLPs were evaluated in hotplate latency test, formalin-induced behavioral, and paw edema tests. Ondansetron, a selective 5-HT3 receptor antagonist; L-NAME, a NOS inhibitor; and naloxone, an opioid antagonist were injected to determine the mechanisms of antinociception and anti-inflammation. We also measured blood glucose levels and performed rotarod test in order to evaluate whether the hypoglycemic effect of GLP compounds or alterations in locomotor activity may affect the latency in hotplate test and activity in formalin test. RESULTS: GLP-1 (0.2 mg/kg) and GLP-2 (0.05, 0.2 mg/kg) significantly increased pain threshold. GLP-1 (0.2 mg/kg) and GLP-2 (0.05, 0.1, 0.2 mg/kg) significantly decreased formalin-induced licking and shaking behaviors. GLP-1 or GLP-2 showed no significant inhibitory action on formalin-induced swelling in paws of mice. Antinociceptive actions of GLP-1 and GLP-2 were significantly decreased with ondansetron and naloxone, and paw shaking behavior significantly increased with naloxone. GLP-1 and GLP-2 did not impair rotarod performance, and did not cause a significant hypoglycemic effect in our normoglycemic mice after rotarod test. CONCLUSION: These finding indicated that the antinociceptive and anti-inflammatory effect of GLP-1 was related to opioidergic system. Antinociceptive effect of GLP-2 was partially related to 5-HT3 serotonergic or opioidergic system in hotplate test. However, the anti-inflammatory effect of GLP-2 was not directly related to 5-HT3, NO or opioids.

Repetitive neonatal pain and reduced maternal care alter brain neurochemistry.

Preterm infants are exposed to many stressors while in the neonatal intensive care unit including pain and reduced maternal care. Both stressors can have a profound negative impact on brain development, and the present study sought to investigate some of the biological mechanisms underlying this phenomenon. Rat pups underwent a series of repetitive needle pokes and/or reduced maternal care through a novel tea-ball infuser encapsulation model during the first four days of life. On postnatal day four, pups were sacrificed and serum was analyzed for corticosterone, while brains were tested for various neurotransmitters and brain metabolites through magnetic resonance spectroscopy. We found that exposure to maternal isolation and neonatal pain produced an increase in serum corticosterone but decreased glutamate levels in the hippocampus and frontal cortex. These alterations in stress responding and neurochemistry in response to the early-life stressors may help explain some of the negative outcomes seen in preterm infants.

Monthly vitamin D supplementation, pain, and pattern of analgesic prescription: secondary analysis from the randomized, double-blind, placebo-controlled Vitamin D Assessment study.

Observational studies suggest that vitamin D deficiency is associated with higher risk of pain. However, evidence on the effect of vitamin D supplementation on pain is limited and contradictory. The aim of this study was to compare the effect of monthly high-dose vitamin D supplementation on a pain impact questionnaire (PIQ-6) score and prescription of analgesics in the general population. We performed a randomized, double-blind, placebo-controlled trial of 5108 community-dwelling participants, aged 50 to 84 years, who were randomly assigned to receive monthly 100,000-IU capsules of vitamin D3 (n = 2558) or placebo (n = 2550) for a median of 3.3 years. The PIQ-6 was administered at baseline, year 1, and final follow-up. Analgesic prescription data were collected from Ministry of Health. There was no difference in mean PIQ-6 score at the end of follow-up (adjusted mean difference: 0.06; P = 0.82) between the vitamin D (n = 2041) and placebo (n = 2014) participants. The proportion of participants dispensed one or more opioids was similar in the vitamin D group (n = 559, 21.9%) compared with placebo (n = 593, 23.3%); the relative risk (RR) adjusted for age, sex, and ethnicity was 0.94 (P = 0.24). Similar results were observed for dispensing of nonsteroidal anti-inflammatory drugs (RR = 0.94; P = 0.24) and other nonopioids (RR = 0.98; P = 0.34). Focusing on vitamin D deficient participants (<50 nmol/L, 24.9%), there was a lower risk of dispensing nonsteroidal anti-inflammatory drugs in the vitamin D group compared with placebo (RR = 0.87; P = 0.009); all other subgroup analyses were not significant. Long-term monthly high-dose vitamin D supplementation did not improve mean PIQ-6 score or reduce analgesic dispensing in the general population.

Effect of vitamin D supplementation on knee osteoarthritis: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: To provide evidence regarding the effect of vitamin D supplementation on symptomatic knee osteoarthritis (OA). METHODS: A systematic review and meta-analysis was performed to quantitatively pool the results from randomized clinical trials. Studies were identified from a search of the Embase, MEDLINE and Web of Science databases up to January 22, 2017, and also from conference abstracts, ClinicalTrials.gov and the reference lists of identified studies. A standardized mean difference (SMD) was used to assess effect sizes, as outcomes were reported on different scales. Depending on the degree of heterogeneity, random-effects or fixed-effects models were used to pool outcomes. RESULTS: Up to January 22, 2017, four clinical trials containing 570 subjects in the vitamin D supplementation group and 560 subjects in the placebo group were identified. All of the included studies were of high quality and had a low risk of bias for each domain. The results indicated that vitamin D supplementation had a statistically significant but small-to-moderate effect on pain control in patients with knee OA (SMD=-0.32, 95% CI: -0.63 to -0.02). However, no effects were observed for the change in tibial cartilage volume (SMD=0.12, 95% CI: -0.05 to 0.29) or joint space width (SMD=0.07, 95% CI: -0.08 to 0.23). The subgroup analysis indicated that vitamin D supplementation had no significant effect regardless of whether patients had sufficient or insufficient serum 25(OH)D levels at baseline. CONCLUSIONS: The results of this study indicate that vitamin D supplementation may not have a clinically significant effect on pain control or structure progression among patients with knee OA. Longer-term clinical trials with rigorous measurement of symptom and radiologic changes are required to further clarify the effect of vitamin D supplementation in patients with symptomatic knee OA and low serum 25(OH)D levels.

Time course of copeptin during a model of experimental pain and hyperalgesia: A randomised volunteer crossover trial.

BACKGROUND: A reliable biomarker for quantifying pain or hyperalgesia has yet to be found. A surrogate marker of arginine vasopressin, copeptin, is elevated in a number of states of physiological and psychological stress and may have a role in quantifying pain and/or hyperalgesia. OBJECTIVES: To evaluate copeptin as a biomarker for pain or hyperalgesia developing after 120 min of sustained electrical stimulation. DESIGN: Secondary analysis of a randomised, double-blinded, crossover trial. SETTING: Single, tertiary university hospital from September 2014 to January 2015. PARTICIPANTS: A total of 16 healthy, opioid-naïve white men with no confounding medication or history of pain. INTERVENTIONS: Copeptin and cortisol were measured five times during an established model of transdermal electrical stimulation designed to assess pain and hyperalgesia. MAIN OUTCOME MEASURES: The primary outcome was the change in copeptin concentration after 120 min of sustained electrical stimulation. Secondary outcomes were copeptin and cortisol concentrations after a subsequent period of rest and analyses of copeptin and cortisol concentrations were made in high-dose and low-dose fentanyl groups separately. RESULTS: Total copeptin concentrations were not significantly elevated after 120 min [9.15 pmol l (interquartile ranges (IQR), 3.45 to 35.45 pmol l); P = 0.150] compared with baseline [6.15 pmol l (IQR, 3.60 to 10.62 pmol l)]. In the high-dose fentanyl group, there was a significant increase in copeptin within individuals [P = 0.001; median, 37.9 pmol l (IQR, 8.1 to 62 pmol l)] after 120 min, and in the low-dose fentanyl group a significant decrease in copeptin concentrations within individuals [P = 0.006; median, 4.7 pmol l (IQR, 3.13 to 9.35 pmol l)]. No correlation between copeptin concentration and either the area under the pain curve or area under the hyperalgesia curve could be found, indicating that the observed differences may be due to other fentanyl-mediated effects. CONCLUSION: Copeptin concentrations do not appear to be associated directly with pain and hyperalgesia. Instead, some fentanyl-mediated effect or effects appear to have greatly increased copeptin concentrations from baseline to 120 min. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02252458.

Investigation of the effect of traditional Chinese medicine on pain and inflammation in chronic nonbacterial prostatitis in rats.

According to traditional Chinese medicine, the symptoms of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CNP/CPPS) may be treated using a cocktail of herbs that stimulate blood circulation ('activating blood circulation formula'). We investigated the effect of three doses of this formula on a rat model of CNP/CPPS. Male Wistar rats were injected with a saline extract of male sex accessory glands on days 0 and 30 to induce prostatitis and then treated daily by gavage between days 32 and 60. Treatment with low, medium and high doses of activating blood circulation formula resulted in an almost total rescue of paw withdrawal threshold at day 60, and treatment with the highest dose also significantly decreased prostate inflammation (assessed histopathologically). We further observed elevated serum prostaglandin E2 levels in the CNP/CPPS model which decreased upon high-dose treatment, and increased Cox-2 expression in the prostate and spinal cord dorsal horn which was rescued in both tissues in the high-dose group and in the prostate in the medium-dose group. These results shed light on a possible mechanism by which activating blood circulation therapy may alleviate pain in a rat model of CNP/CPPS by downregulating Cox-2 expression in the spinal cord, thereby raising the pain threshold. Further research will be needed to fully characterise the mechanism by which activating blood circulation therapy produces this therapeutic effect.

The antinociceptive effect and mechanism of action of SY0916.

Pain greatly affects the quality of life of people worldwide. Despite their demonstrated efficacy, currently used opioid drugs and nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently associated with several adverse events. The identification of new therapeutic targets and the development of corresponding analgesics may represent novel approaches for effectively treating pain. SY0916 is a novel compound that was designed and synthesized by the Institute of Materia Medica, Chinese Academy of Medical Sciences. As demonstrated by the hot plate test, tail-flick test and the formalin test, SY0916 exerted strong peripheral and central antinociceptive effects. Western blot, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) results indicate that SY0916 induces its peripheral antinociceptive effect by suppressing the peripheral activity of inflammatory mediators such as prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α) and 5-hydroxytryptamine (5-HT). Moreover, its central antinociceptive effect might be mediated by the down-regulation of PGE2 and TNF-α expression and the inhibition of p-p38 and NF-κB pathway signaling in glial cells. These findings demonstrate that SY0916 may serve as a promising analgesic candidate drug.

Determination of the coenzyme Q10 status in a large Caucasian study population.

Coenzyme Q10 (CoQ10 ) exists in a reduced (ubiquinol) and an oxidized (ubiquinone) form in all human tissues and functions, amongst others, in the respiratory chain, redox-cycles, and gene expression. As the status of CoQ10 is an important risk factor for several diseases, here we determined the CoQ10 status (ubiquinol, ubiquinone) in a large Caucasian study population (n = 1,911). The study population covers a wide age range (age: 18-83 years, 43.4% men), has information available on more than 10 measured clinical phenotypes, more than 30 diseases (presence vs. absence), about 30 biomarkers, and comprehensive genetic information including whole-genome SNP typing (>891,000 SNPs). The major aim of this long-term resource in CoQ10 research is the comprehensive analysis of the CoQ10 status with respect to integrated health parameters (i.e., fat metabolism, inflammation), disease-related biomarkers (i.e., liver enzymes, marker for heart failure), common diseases (i.e., neuropathy, myocardial infarction), and genetic risk in humans. Based on disease status, biomarkers, and genetic variants, our cohort is also useful to perform Mendelian randomisation approaches. In conclusion, the present study population is a promising resource to gain deeper insight into CoQ10 status in human health and disease.

Effect of high-voltage electrical stimulation on the albumin and histamine serum concentrations, edema, and pain in acute joint inflammation of rats.

BACKGROUND: The mechanism by which high-voltage electrical stimulation (HVPC) acts on edema reduction is unknown. OBJECTIVE: To assess the effect of HVPC with negative polarity (-) applied to the ankle of rats with acute joint inflammation. METHOD: Sixty-four rats were divided into four groups (n=16): inflamed+HVPC(-), 0.03 mL application of ι-carrageenan (3%) to the tibiotarsal joint plus HVPC(-); inflamed+HVPC placebo, carrageenan application and HVPC placebo; normal+HVPC(-), HVPC application(-); and normal control, no intervention. The HVPC(-) 100 Hz at a submotor level was applied daily for 45 min on three consecutive days. The variables were pain, hind-foot volume, and serum histamine and albumin assessed before and during the 48 hours following inflammation. The variables were compared using the t test, one-way ANOVA, nested ANOVA for repeated measures, and the post hoc Bonferroni test. Analysis of covariance was applied to adjust the effects of HVPC(-) by measurements of pain, inflammation, albumin, and histamine at 24 h, and the final weight was compared to the other groups. The significance level was set at p<0.05. RESULTS: There were no differences between the inflamed+HVPC(-) and inflamed+HVPC placebo groups in terms of pain or edema (p>0.05). Albumin was reduced in the groups that received the intervention, but there was no differences between them. There was only a 24 hour increase in histamine with the normal+HVPC(-) (p=0.0001) and inflamed+HVPC placebo groups (p=0.01) compared to the normal control group. CONCLUSIONS: The results of the present study suggest that HVPC(-) with the parameters employed did not reduce pain or edema and did not change serum albumin or histamine levels,, which indicates the inability of this resource to have a positive effect when treating treat acute joint inflammation.

Low vitamin D levels are associated with higher opioid dose in palliative cancer patients--results from an observational study in Sweden.

BACKGROUND: Vitamin D deficiency is common among palliative cancer patients and has been connected to an increased risk for pain, depressions and infections. Therefore we wanted to test the hypothesis that low 25-hydroxyvitamin D (25OHD) levels are associated with higher opioid dose, higher infectious burden and impaired quality of life in palliative cancer patients. The secondary aim was to investigate the association between 25OHD-levels and survival time. METHOD: In this prospective, observational study in palliative cancer-patients (n = 100) we performed univariate and multiple linear regression analysis to assess the association of 25OHD levels with opioid dose, infectious burden (antibiotic consumption), quality of life (Edmonton Symptom Assessment Scale, ESAS) and survival time, controlling for potential confounding factors. RESULTS: The median 25OHD level was 40 nmol/L (range 8-154 nmol/L). There was a significant association between 25OHD levels and opioid dose, beta coefficient -0.67; p=0.02; i.e. a low 25OHD level was associated with a higher opioid dose. This association remained significant after adjustment for stage of the cancer disease in a multivariate analysis, beta coefficient -0.66; p = 0.04. There was no association between 25OHD levels and antibiotic use or quality of life. Univariate cox regression analysis showed a weak correlation between survival time and 25OHD levels (p<0.05). However, decreased albumin levels and increased CRP levels were superior markers to predict survival time; p<0.001 for both analyses. CONCLUSION: Low 25OHD-levels are associated with increased opioid consumption in palliative cancer patients. Future interventional studies are needed to investigate if pain can be reduced by vitamin D supplementation in these patients. In addition, this study confirms previous findings that low albumin and increased CRP levels are useful markers for survival time in palliative cancer patients.

Effect of high-voltage electrical stimulation on the albumin and histamine serum concentrations, edema, and pain in acute joint inflammation of rats

BACKGROUND: The mechanism by which high-voltage electrical stimulation (HVPC) acts on edema reduction is unknown. OBJECTIVE: To assess the effect of HVPC with negative polarity (-) applied to the ankle of rats with acute joint inflammation. METHOD: Sixty-four rats were divided into four groups (n=16): inflamed+HVPC(-), 0.03 mL application of ι-carrageenan (3%) to the tibiotarsal joint plus HVPC(-); inflamed+HVPC placebo, carrageenan application and HVPC placebo; normal+HVPC(-), HVPC application(-); and normal control, no intervention. The HVPC(-) 100 Hz at a submotor level was applied daily for 45 min on three consecutive days. The variables were pain, hind-foot volume, and serum histamine and albumin assessed before and during the 48 hours following inflammation. The variables were compared using the t test, one-way ANOVA, nested ANOVA for repeated measures, and the post hoc Bonferroni test. Analysis of covariance was applied to adjust the effects of HVPC(-) by measurements of pain, inflammation, albumin, and histamine at 24 h, and the final weight was compared to the other groups. The significance level was set at p<0.05. RESULTS: There were no differences between the inflamed+HVPC(-) and inflamed+HVPC placebo groups in terms of pain or edema (p>0.05). Albumin was reduced in the groups that received the intervention, but there was no differences between them. There was only a 24 hour increase in histamine with the normal+HVPC(-) (p=0.0001) and inflamed+HVPC placebo groups (p=0.01) compared to the normal control group. CONCLUSIONS: The results of the present study suggest that HVPC(-) with the parameters employed did not reduce pain or edema and did not change serum albumin or histamine levels,, which indicates the inability of this resource to have a positive effect when treating treat acute joint inflammation. .

Vitamin D deficiency and acute vaso-occlusive complications in children with sickle cell disease.

BACKGROUND: Vitamin D is increasingly recognized for its roles in non-skeletal disorders. Patients with sickle cell disease (SCD) have a high prevalence of vitamin D deficiency but data are limited with respect to possible associations between low vitamin D and acute vaso-occlusive complications. We examined whether vitamin D deficiency is associated with acute pain and acute chest syndrome (ACS) in children with SCD. PROCEDURE: A cross-sectional study was conducted in 95 children with SCD who had serum 25-hydroxyvitamin D (25-OHD) measured during comprehensive care examinations. History of acute pain and ACS within two years of obtaining 25-OHD was collected. Associations between 25-OHD levels and acute vaso-occlusive events were analyzed by logistic regression. Odds ratios and 95% confidence intervals were calculated for the risk of pain and ACS associated with vitamin D deficiency (25-OHD <20 ng/ml). RESULTS: Subjects were 3-20 years old (median 10.6); 48 males, 47 females; 46 African, 49 Hispanic; 72 SS, 20 SC, 1 S/ß(0) Thalassemia, and 2 S/ß(+) Thalassemia. Median 25-OHD was 16 ng/ml. Fifty-six (59%) were vitamin D-deficient. Thirty-one (33%) and 29 (31%) had at least one episode of pain and ACS, respectively. Serum 25-OHD was significantly associated with pain (P = 0.0121) but not with ACS (P = 0.628). Of those with pain, 73% (23/31) were vitamin D-deficient while 26% (8/31) had 25-OHD ≥20 ng/ml (P = 0.04, OR = 2.7, 95%CI = 1.05-6.94). CONCLUSIONS: Our findings emphasize the high prevalence of vitamin D deficiency and its potential association with acute pain in SCD. Correcting low vitamin D may offer a simple, low-cost intervention to help reduce acute vaso-occlusive complications.

The effects of an oral preparation containing hyaluronic acid (Oralvisc®) on obese knee osteoarthritis patients determined by pain, function, bradykinin, leptin, inflammatory cytokines, and heavy water analyses.

The purpose of this study was to determine the effects of an oral preparation containing hyaluronic acid on osteoarthritic knee joint pain and function as well as changes in inflammatory cytokines, bradykinin, and leptin. We also used heavy water to determine the turnover rates of glycosaminoglycans in synovial fluid. This was a double-blind, randomized, placebo-controlled study of 40 subjects over a period of 3 months. Visual analog scale, Western Ontario McMaster pain, and WOMAC function scores were recorded. Serum and synovial fluid were measured by enzyme-linked immunosorbent assays for inflammatory cytokines, bradykinin, and leptin. In 20 subjects, terminal heavy water ingestion was used for spectral analyses of serum and joint fluid samples. There were statistically significant improvements in pain and function. Both serum and synovial fluid samples showed significant decreases for a majority of inflammatory cytokines, leptin, and bradykinin in the oral hyaluronic acid preparation group. Heavy water analyses revealed a significant decrease in hyaluronic acid turnover in the synovial fluid of the treatment group. A preparation containing hyaluronic acid and other glycosaminoglycans holds promise for a safe and effective agent for the treatment for patients with knee osteoarthritis and who are overweight. Further studies will be required to see whether this is a disease-modifying agent.

Effects of guided imagery on biobehavioral factors in women with fibromyalgia.

Women diagnosed with fibromyalgia (N = 72) participated in a 10-week randomized trial to examine the effectiveness of guided imagery on self-efficacy, perceived stress, and selected biobehavioral factors (FMS symptoms; immune biomarkers). Participants in both guided imagery and usual care control conditions completed measures and donated 3 cc of blood at baseline, 6- and 10-weeks. A mixed effects linear model to test for differences between groups for all behavioral and biologic variables demonstrated that after 10 weeks of daily intervention use, guided imagery participants reported statistically significant increases in self-efficacy and statistically significant decreases in stress, fatigue, pain, and depression. There were no statistically significant changes in biomarker levels, although total group C-reactive protein was elevated at baseline (4.7 mg/L), indicating an inflammatory process. Subsequent studies should be undertaken to more fully elucidate the biobehavioral aspects of nonpharmacological intervention effectiveness.