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We investigated whether atorvastatin, a plasma cholesterol lowering and anti-inflammatory drug, attenuates lipopolysaccharide-induced fever in rats.Sprague–Dawley rats, implanted with abdominal temperature-sensitive telemeters, were administered either lipopolysaccharide and placebo , lipopolysaccharide and atorvastatin , saline and placebo , or saline and atorvastatin .Atorvastatin (100mgkg-1) was administered orally, as a suspension in a flavoured gelatine cube (placebo cubes contained no drug), 90min before intraperitoneal injection of pyrogen (Salmonella typhosa lipopolysaccharide, 75μgkg-1) or sterile saline.Atorvastatin did not disrupt normal thermoregulation. Atorvastatin also did not attenuate lipopolysaccharide-induced changes in body temperature and cage activity. [Copyright &y& Elsevier]

To determine the relationship between arterial blood colour [as defined by the International Commission on Illumination (CIE) L∗a∗b∗ colour space] and haemoglobin oxygen saturation [functional saturation (SaO 2) and fractional saturation (FO 2 Hb)], and if arterial blood colour can be used to predict arterial haemoglobin oxygen saturation. Descriptive study as an adjunct to two prospective randomized crossover studies. A group of 10 wild caught adult female impala (Aepyceros melampus) weighing 34.1 ± 5.2 kg (mean ± standard deviation). Impala were immobilized with potent opioids (0.09 mg kg–1 of etorphine or thiafentanil). A total of 163 arterial blood samples were collected anaerobically into heparinized syringes from arterial cannulae and analysed immediately using spectrocolourimetry and co-oximetry. Data were analysed by modelling the relationship between predicted arterial blood colour CIE L∗a∗b∗ components and SaO 2 and FO 2 Hb. The models were then used to predict values for L∗, a∗ and b∗ to produce a colour palette for the range of SaO 2 and FO 2 Hb used. The modified version of the Farnsworth-Munsell hue test was used to assess the subjective ordering of the resulting colour palette by 20 observers. The second-order polynomial (quadratic) model produced the best fit for all three arterial blood colour CIE L∗a∗b∗ components for both SaO 2 and FO 2 Hb. The regression models were used to generate predicted arterial blood colour CIE L∗a∗b∗ components for the midpoint of each decile over a range of SaO 2 and FO 2 Hb percentages (15% to 95%). The resulting colour palettes were correctly ordered by all observers in the SaO 2 range of 45–95% saturation. An association between arterial blood colour (as defined by CIE L∗a∗b∗ components) and SaO 2 and FO 2 Hb exists, and arterial blood colour can be used to give a clinically useful estimate of arterial haemoglobin oxygen saturation in impala. [ABSTRACT FROM AUTHOR]

Abstract In experiments on pain, participants are frequently exposed to nonpainful and painful stimuli; however, the conventional pain-rating scales lack a nonpainful range and a clear point of transition from nonpainful to painful events. The Sensation and Pain Rating Scale (SPARS) assesses the full stimulus intensity range, extending from no sensation (rating: –50) to worst pain imaginable (rating: +50), and it explicitly identifies pain threshold (rating: 0). Here, we tested the SPARS in 2 experiments by using laser heat stimuli to establish its stimulus–response characteristics (Experiment 1, N = 19, 13 stimulus intensities applied 26 times each across a 1–4 J range), and compared it to 0 to 100 scales that assess nonpainful (0: no sensation, 100: pain) and painful (0: no pain, 100: worst pain imaginable) events (Experiment 2, N = 7, 9 stimulus intensities applied 36 times each across a 1.5–4.5 J range). Despite high inter- and intraindividual variations, we found a reasonably consistent curvilinear stimulus–response relationship (the curve flattens around pain threshold), with stable response characteristics across the range of the scale. The SPARS ratings transformed to a 0 to 100 range tended to be lower than the 0 to 100 pain rating scale in the noxious stimulus intensity range and greater than the 0 to 100 nonpainful sensation scale in the non-noxious stimulus range, likely reflecting differences in scale dimensionality. The SPARS overcomes limitations in scale range inherent to conventional pain rating scales. As such, it is well suited to experimental studies that must quantify a wider range of perceptual intensity or distinguish between painful and nonpainful events. Perspective This article presents the stimulus–response characteristics of a new scale designed to allow participants to rate a range of nonpainful and painful stimuli. The scale could be useful for research that involves exposing participants to a range of stimulation intensities or requires a clear distinction between nonpainful and painful events. [ABSTRACT FROM AUTHOR]

In experiments on pain, participants are frequently exposed to nonpainful and painful stimuli; however, the conventional pain-rating scales lack a nonpainful range and a clear point of transition from nonpainful to painful events. The Sensation and Pain Rating Scale (SPARS) assesses the full stimulus intensity range, extending from no sensation (rating: -50) to worst pain imaginable (rating: +50), and it explicitly identifies pain threshold (rating: 0). Here, we tested the SPARS in 2 experiments by using laser heat stimuli to establish its stimulus-response characteristics (Experiment 1, N = 19, 13 stimulus intensities applied 26 times each across a 1-4 J range), and compared it to 0 to 100 scales that assess nonpainful (0: no sensation, 100: pain) and painful (0: no pain, 100: worst pain imaginable) events (Experiment 2, N = 7, 9 stimulus intensities applied 36 times each across a 1.5-4.5 J range). Despite high inter- and intraindividual variations, we found a reasonably consistent curvilinear stimulus-response relationship (the curve flattens around pain threshold), with stable response characteristics across the range of the scale. The SPARS ratings transformed to a 0 to 100 range tended to be lower than the 0 to 100 pain rating scale in the noxious stimulus intensity range and greater than the 0 to 100 nonpainful sensation scale in the non-noxious stimulus range, likely reflecting differences in scale dimensionality. The SPARS overcomes limitations in scale range inherent to conventional pain rating scales. As such, it is well suited to experimental studies that must quantify a wider range of perceptual intensity or distinguish between painful and nonpainful events. PERSPECTIVE: This article presents the stimulus-response characteristics of a new scale designed to allow participants to rate a range of nonpainful and painful stimuli. The scale could be useful for research that involves exposing participants to a range of stimulation intensities or requires a clear distinction between nonpainful and painful events. [ABSTRACT FROM AUTHOR]

Cross-sectional studies report that pain in ambulatory HIV-infected individuals is frequent and often undermanaged. Expanding access to HIV treatment in developing countries means that infected individuals are living longer, but there is a dearth of pain-directed studies from developing countries that describe the progression of pain and its treatment over any period of time. The aim of this study was to characterize the progression of pain and its treatment over a 6-month period in 92 ambulatory HIV-positive patients attending an outpatient clinic in Johannesburg, South Africa. We used the Wisconsin Brief Pain Questionnaire to assess changes in pain intensity, pain sites, pain interference, and pain treatment. At visit 1, pain was present in 78 of 92 patients (85%). Of the 78 patients with pain, 67 had moderate or severe pain (86%) and pain affected two or more body sites simultaneously in 57 of these patients (73%). After 6 months, pain prevalence still was high, but had fallen to 50 patients (54%). Of the patients with pain at visit 2, the proportion with moderate or severe pain (82%), or two or more pain sites (62%) had decreased. Analgesic use was low at both time points (5% and 25% analgesic use at visit 1 and 2, respectively). Despite the high pain burden, pain interference in daily activities was very low across the period assessed. The burden of pain in this cohort of ambulatory HIV-positive patients was high, but there were significant reductions in pain burden over time. [ABSTRACT FROM AUTHOR]

Abstract: We have investigated whether long-term oral administration of the nucleoside reverse transcriptase inhibitor (NRTI) stavudine affects nociception in Sprague-Dawley rats, and whether any changes of nociception are accompanied by deterioration in activity and appetite. Stavudine (50 mg kg−1) was administered to rats orally once daily for six weeks in gelatine cubes. Mechanical hyperalgesia of the tail was assessed using a bar algometer, and thermal hyperalgesia by tail immersion in 49 °C water. Withdrawal latencies were compared to those of rats receiving placebo gelatine cubes. Withdrawal latencies to the noxious thermal challenge were not affected by stavudine, but those to the mechanical challenge were significantly decreased in rats receiving stavudine, compared to rats receiving placebo, from week three to week six of drug administration (P <0.05, ANCOVA with Newman Keuls post-hoc comparisons). The overall condition of the rats was assessed by recording daily voluntary wheel running distance and maximum running speed, food intake and body mass. Daily stavudine administration did not adversely affect voluntary running activity, appetite or growth. We have shown that long-term daily oral administration of the NRTI stavudine results in mechanical hyperalgesia in rats within three weeks without affecting appetite, growth and physical activity. [Copyright &y& Elsevier]

Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January, 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fixed-effects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-reviewed journals reported greater effects than did unpublished studies ( r 2 9·3%, p=0·009). Trial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, final quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These findings permitted a strong recommendation for use and proposal as first-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest efficacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profiling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain. [ABSTRACT FROM AUTHOR]

Abstract: Context: HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of both HIV and neurotoxic antiretroviral medications such as stavudine. Objectives: To determine the prevalence, risk factors, and clinical characteristics of symptomatic HIV-SN in a Black South African cohort of patients exposed to stavudine. Methods: HIV-positive Black South Africans (n =395) who had received stavudine for at least six months were recruited at the Virology Clinic of the Charlotte Maxeke Academic Johannesburg Hospital, South Africa, and screened for neuropathy using the AIDS Clinical Trials Group neuropathy screening tool. HIV-SN was defined as present if the patient had both symptoms and signs of peripheral neuropathy. If present, the distribution and intensity of symptoms were recorded. In addition, anthropomorphic, demographic, and clinical information were recorded and analyzed as risk factors. Results: The prevalence of symptomatic HIV-SN was 57% (226 of 395). Increasing age and height were independently associated with the development of SN among patients who had used stavudine. Pain was the primary symptom reported by participants with HIV-SN (76%, 172 of 226), followed by numbness (48%, 108 of 226), and pins and needles (46%, 105 of 226). About three-quarters of participants rated their symptoms as being of moderate to severe intensity. Symptoms were always present in the feet and only 23% experienced symptoms proximal to the feet. Conclusion: HIV-SN was common in this population and frequently associated with moderate to severe pain in the feet. HIV-SN was significantly associated with increasing age and height, factors that could be measured at no added cost prior to stavudine prescription, allowing higher risk patients to be offered priority access to nonneurotoxic drugs. [Copyright &y& Elsevier]

Irregular work times promote inconsistent completion of the Pittsburgh Sleep Quality Index (PSQI) among shift workers. We aimed to demonstrate the importance of testing the internal consistency and construct validity of the PSQI and of the Epworth Sleepiness Scale (ESS) by presenting the methodology in a sample of long-haul truckers in South Africa. Internal consistency of the questionnaires was assessed by Cronbach's alpha (defined as raw alpha≥0.70), and construct validity by factor analysis. 302 participants (49.3%) reported at least one night shift/week. Overall, the PSQI and ESS's alpha were 0.42 and 0.85, respectively. The factors explained 19.6% of 57.0% of the variance. The PSQI's alpha was 0.46 in night shift workers and 0.38 in non-night shift workers. In this occupational group, the PSQI must be used with caution. Testing the internal consistency and construct validity among the assessed population seems necessary. Sleep questionnaires adapted to shift workers should be preferred. [ABSTRACT FROM AUTHOR]

Adaptive heterothermy and selective brain cooling are regarded as important thermal adaptations of large arid-zone mammals. Adaptive heterothermy, a process which reduces evaporation by storing body heat, ought to be enhanced by ambient heat load and by water deficit, but most mammals studied fail to show at least one of those attributes. Selective brain cooling, the reduction of brain temperature below arterial blood temperature, is most evident in artiodactyls, which possess a carotid rete, and traditionally has been considered to protect the brain during hyperthermia. The development of miniature ambulatory data loggers for recording body temperature allows the temperatures of free-living wild mammals to be measured in their natural habitats. All the African ungulates studied so far, in their natural habitats, do not exhibit adaptive heterothermy. They have low-amplitude nychthemeral rhythms of temperature, with mean body temperature over the night exceeding that over the day. Those with carotid retes (black wildebeest, springbok, eland) employ selective brain cooling but zebra, without a rete, do not. None of the rete ungulates, however, seems to employ selective brain cooling to prevent the brain overheating during exertional hyperthermia. Rather, they use it at rest, under moderate heat load, we believe in order to switch body heat loss from evaporative to non-evaporative routes. [Copyright &y& Elsevier]