Antinociceptive and anti-inflammatory properties of 7-hydroxycoumarin in experimental animal models: potential therapeutic for the control of inflammatory chronic pain

Objectives In the present study we investigated the anti nociceptive, anti-inflammatory and antipyretic effects of 7-hydroxycoumarin (7-HC) in animal models. Methods The effects of oral 7-HC were tested against acetic acid-induced writhing, formalin test, tail flick test, complete Freund`s adjuvant (CFA)-induced hypemociception, carrageenan-induced paw oedema, lipopolysaccharide-induced fever and the rota rod test. Key findings 7-HC (3-60 mg/kg) produced a dose-related antinociception against acetic acid-induced writhing in mice and in the formalin test. In contrast, treatment with 7-HC did not prevent thermal nociception in the tail flick test. A single treatment with 7-HC, 60 mg/kg, produced a long-lasting antinociceptive effect against CFA-induced hypernociception, a chronic inflammatory pain stimulus. Notably, at 60 mg/kg per day over 4 days the administration of 7-HC produced a continuous antinociceptive effect against CFA-induced hypernociception. 7-HC (30-120 mg/kg) produced anti-inflammatory and antipyretic effects against carrageenan-induced inflammation and lipopolysaccharide-induced fever, respectively. Moreover, 7-HC was found to be safe with respect to ulcer induction. In the rota rod test, 7-HC-treated mice did not show any motor performance alterations. Conclusions The prolonged antinociceptive and anti-inflammatory effects of 7-HC, in association with its low ulcerogenic activity, indicate that this molecule might be a good candidate for development of new drugs for the control of chronic inflammatory pain and fever.

Does anticipation of back pain predispose to back trouble?

Limb movement imparts a perturbation to the body. The impact of that perturbation is limited via anticipatory postural adjustments. The strategy by which the CNS controls anticipatory postural adjustments of the trunk muscles during limb movement is altered during acute back pain and in people with recurrent back pain, even when they are pain free. The altered postural strategy probably serves to protect the spine in the short term, but it is associated with a cost and is thought to predispose spinal structures to injury in the long term. It is not known why this protective strategy might occur even when people are pain free, but one possibility is that it is caused by the anticipation of back pain. In eight healthy subjects, recordings of intramuscular EMG were made from the trunk muscles during single and repetitive arm movements. Anticipation of experimental back pain and anticipation of experimental elbow pain were elicited by the threat of painful cutaneous stimulation. There was no effect of anticipated experimental elbow pain on postural adjustments. During anticipated experimental back pain, for single arm movements there was delayed activation of the deep trunk muscles and augmentation of at least one superficial trunk muscle. For repetitive arm movements, there was decreased activity and a shift from biphasic to monophasic activation of the deep trunk muscles and increased activity of superficial trunk muscles during anticipation of back pain. In both instances, the changes were consistent with adoption of an altered strategy for postural control and were similar to those observed in patients with recurrent back pain. We conclude that anticipation of experimental back pain evokes a protective postural strategy that stiffens the spine. This protective strategy is associated with compressive cost and is thought to predispose to spinal injury if maintained long term. © Guarantors of Brain 2004; all rights reserved

Delayed postural contraction of transversus abdominis in low back pain associated with movement of the lower limb

The temporal parameters of the response of the trunk muscles associated with movement of the lower limb were investigated in people with and without low back pain (LBP). The weight shift component of the task was completed voluntarily prior to a stimulus to move to allow investigation of the movement component of the response. In the control subjects the onset of electromyographic (EMG) activity of all trunk muscles preceded that of the muscle responsible for limb movement, thus contributing to the feed forward postural response. The EMG onset of transversus abdominis was delayed in the LBP subjects with movement in each direction, while the EMG onsets of rectus abdominis, erector spinae, and oblique abdominal muscles were delayed with specific movement directions. This result provides evidence of a change in the postural control of the trunk in people with LBP.

Incorporating cognitive-behavioral therapy with occupational therapy: A comparative study with patients with low back pain

This paper reports on the implementation of a psychoeducational program utilizing cognitive-behavioral principles. The efficacy of this psychoeducational treatment program in modifying dysfunctional attitudes in patients with chronic low back pain was examined using a two-group pretest posttest design with a follow-lip at 3 months Thirty patients (average age = 44.37 SD = 13.71) participated in the study, with 15 in the psychoeducational treatment group and 15 in the placebo control group. These two conditions were added on to an existing eclectic inpatient pain management program. After assessment on the IPAM (The Integrated Psychosocial Assessment Model), scores were reduced to multivariate composite scores on the factors of illness behavior depressed and negative cognitions, and acute pain strategies. Results of a group x time repeated measures analysis of variance for the three pain factors revealed a significant main effect for group (F(23,1) = 5.00 p < .04), tempered by a significant interaction between group and rime on the 'depressed and negative' pain factor (F(23,1) = 4.77 p < .04). Patients in the treatment group improved significantly over time and significantly more than the placebo control group patients at posttreatment. Results provide support for the program in increasing patients' feelings of control over their pain and the use of positive coping strategies, while reducing perceived helplessness, depression, disability, and pain intensity.

Cerebrospinal fluid and plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in patients before and after initiation of intracerebroventricular morphine for cancer pain management

Twenty-three patients treated with intracerebroventricular (ICV) morphine in this study not only obtained excellent pain relief without rapid increases in dose, but also experienced a reduction in morphine-related side effects. By 24 h after initiation of ICV morphine, the mean trough cerebrospinal fluid (CSF) morphine concentration (approximately 20 mu M) was 50-fold higher than the baseline concentration (approximately 0.4 mu M), and the CSF concentration of morphine-6-glucuronide (M6G) was undetectable (

Fluctuations in heroin purity and the incidence of fatal heroin overdose

In order to determine the role played by heroin purity in fatal heroin overdoses, time series analyses were conducted on the purity of street heroin seizures in south western Sydney and overdose fatalities in that region. A total of 322 heroin samples were analysed in fortnightly periods between February 1993 to January 1995. A total of 61 overdose deaths occurred in the region in the study period. Cross correlation plots revealed a significant correlation of 0.57 at time lag zero between mean purity of heroin samples per fortnight and number of overdose fatalities. Similarly, there was a significant correlation of 0.50 at time lag zero between the highest heroin purity per fortnight and number of overdose fatalities. The correlation between range of heroin purity and number of deaths per fortnight was 0.40. A simultaneous multiple regression on scores adjusted for first order correlation indicated both the mean level of heroin purity and the range of heroin purity were independent predictors of the number of deaths per fortnight. The results indicate that the occurrence of overdose fatalities was moderately associated with both the average heroin purity and the range of heroin purity over the study period. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

Trends in the incidence, severity, and short-term outcome of stroke in Perth, Western Australia

Background and Purpose-This report describes trends in the key indices of cerebrovascular disease over 6 years from the end of the 1980s in a geographically defined segment of the city of Perth, Western Australia. Methods-Identical methods were used to find and assess all cases of suspected stroke in a population of approximately 134 000 residents in a triangular area of the northern suburbs of Perth. Case fatality was measured as vital status at 28 days after the onset of symptoms. Data for first-ever strokes and for all strokes for equivalent periods of 12 months in 1989-1990 and 1995-1996 were compared by age-standardized rates and proportions and Poisson regression. Results-There were 355 strokes in 328 patients and 251 first-ever strokes (71%) for 1989-1990 and 290 events in 281 patients and 213 first-ever strokes (73%) for 1995-1996. In Poisson models including age and period, overall trends in the incidence of both first-ever strokes (rate ratio = 0.75; 95% confidence limits, 0.63, 0.90) and all strokes (rate ratio = 0.73; 95% confidence limits, 0.62, 0.85) were obviously significant, but only the changes in men were independently significant. Case fatality did not change, and the balance between hemorrhagic and occlusive strokes in 1995-1996 was almost indistinguishable from that observed in 1989-1990. Conclusions-Our results, which are the only longitudinal population-based data available for Australia for key indices of stroke, suggest that it is a change in the frequency of stroke, rather than its outcome, that is chiefly responsible nationally for the fall in mortality from cerebrovascular disease.

High HIV incidence and prevalence among young women in rural South Africa: Developing a cohort for intervention trials

Objective: To measure prevalence and model incidence of HIV infection. Setting: 2013 consecutive pregnant women attending public sector antenatal clinics in 1997 in Hlabisa health district, South Africa. Historical seroprevalence data, 1992-1995. Methods: Serum remaining from syphilis testing was tested anonymously for antibodies to HIV to determine seroprevalence. Two models, allowing for differential mortality between HIV-positive and HIV-negative people, were used. The first used serial seroprevalence data to estimate trends in annual incidence. The second, a maximum likelihood model, took account of changing force of infection and age-dependent risk of infection, to estimate age-specific HIV incidence in 1997. Multiple logistic regression provided adjusted odds ratios (OR) for risk factors for prevalent HIV infection. Results: Estimated annual HIV incidence increased from 4% in 1992/1993 to 10% in 1996/1997. In 1997, highest age-specific incidence was 16% among women aged between 20 and 24 years. in 1997, overall prevalence was 26% (95% confidence interval [CI], 24%-28%) and at 34% was highest among women aged between 20 and 24 years. Young age (<30 years; odds ratio [OR], 2.1; p = .001), unmarried status (OR 2.2; p = .001) and living in less remote parts of the district (OR 1.5; p = .002) were associated with HIV prevalence in univariate analysis. Associations were less strong in multivariate analysis. Partner's migration status was not associated with HIV infection. Substantial heterogeneity of HIV prevalence by clinic was observed (range 17%-31%; test for trend, p = .001). Conclusions: This community is experiencing an explosive HIV epidemic. Young, single women in the more developed parts of the district would form an appropriate cohort to test, and benefit from, interventions such as vaginal microbicides and HIV vaccines.

Delayed onset of electromyographic activity of vastus medialis obliquus relative to vastus lateralis in subjects with patellofemoral pain syndrome

Objective: To determine whether electromyographic (EMG) onsets of vastus medialis obliquus (VMO) and vastus lateralis (VL) are altered in the presence of patellofemoral pain syndrome (PFPS) during the functional task of stair stepping. Design: Cross-sectional. Setting: University laboratory. Patients: Thirty-three subjects with PFPS and 33 asymptomatic controls. Interventions: Subjects ascended and descended a set of stairs-2 steps, each 20-cm high-at usual stair-stepping pace. EMG readings of VMO and VL taken on middle stair during step up (concentric contraction) and step down (eccentric contraction). Main Outcome Measures: Relative difference in onset of surface EMG activity of VMO compared with VL during a stair-stepping task. EMG onsets were determined by using a computer algorithm and were verified visually. Results: In the PFPS population, the EMG onset of VL occurred before that of VMO in both the step up and step down phases of the stair-stepping task (p < .05). In contrast, no such differences occurred in the onsets of EMG activity of VMO and VL in either phase of the task for the control subjects. Conclusion: This finding supports the hypothesized relationship between changes in the timings of activity of the vastimuscles and PFPS. This finding provides theoretical rationale to support physiotherapy treatment commonly used in the management of PFPs.

A model for predicting the future incidence of coronary heart disease within percentiles of coronary heart disease risk

Background We present a method (The CHD Prevention Model) for modelling the incidence of fatal and nonfatal coronary heart disease (CHD) within various CHD risk percentiles of an adult population. The model provides a relatively simple tool for lifetime risk prediction for subgroups within a population. It allows an estimation of the absolute primary CHD risk in different populations and will help identify subgroups of the adult population where primary CHD prevention is most appropriate and cost-effective. Methods The CHD risk distribution within the Australian population was modelled, based on the prevalence of CHD risk, individual estimates of integrated CHD risk, and current CHD mortality rates. Predicted incidence of first fatal and nonfatal myocardial infarction within CHD risk strata of the Australian population was determined. Results Approximately 25% of CHD deaths were predicted to occur amongst those in the top 10 percentiles of integrated CHD risk, regardless of age group or gender. It was found that while all causes survival did not differ markedly between percentiles of CHD risk before the ages of around 50-60, event-free survival began visibly to differ about 5 years earlier. Conclusions The CHD Prevention Model provides a means of predicting future CHD incidence amongst various strata of integrated CHD risk within an adult population. It has significant application both in individual risk counselling and in the identification of subgroups of the population where drug therapy to reduce CHD risk is most cost-effective. J Cardiovasc Risk 8:31-37 (C) 2001 Lippincott Williams & Wilkins.