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BackgroundNew 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.MethodsBetween 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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January, 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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.Findings229 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 Studies published in peer-reviewed journals reported greater effects than did unpublished studies (r(2) 9·3%, p=0·009).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.InterpretationOur 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.FundingNeuPSIG of the International Association for the Study of Pain.

Background: There are few studies on chronic pain prevalence in people living with HIV, and there are no studies comparing chronic pain prevalence in an HIV‐infected group (HIV+) to that found in an uninfected group (HIV−) in the same population. This study was undertaken to (1) estimate the chronic pain prevalence in HIV+ individuals and (2) compare chronic pain prevalence between HIV+ and HIV− groups in a population. Methods: Individuals ≥15 years old were recruited using multi‐stage probability sampling in the 2016 South African Demographic and Health Survey. In an interview, participants were asked whether they currently had pain or discomfort, and if so, whether that pain or discomfort had persisted for at least 3 months (operational definition of chronic pain). Blood samples were taken from a volunteering sub‐sample for HIV testing. Results: A total of 6584 of 12,717 eligible individuals answered the questionnaire and were tested for HIV. Mean age: 39.1 years (95% confidence interval [CI]: 38.3–39.9), per cent female: 55% (95% CI: 52–56) and tested HIV+: 19% (95% CI: 17–20). The prevalence of chronic pain was 19% (95% CI: 16–23) in the HIV+ group, which was similar to that found in the HIV− group (20% [95% CI: 18–22]; odds ratio [adjusted for age, sex, socio‐economic status] = 0.93 [95% CI: 0.74–1.17], p‐value = 0.549). Conclusion: The prevalence of chronic pain in South Africans living with HIV was approximately 20%, and having HIV was not associated with an increased risk of chronic pain. Significance: Using data from a large, national, population‐based study in South Africa, I show for the first time that the prevalence of chronic pain in that population did not differ materially between the part of the population that was living with HIV compared with their uninfected counterparts (both approximately 20%). These findings run counter to the dogma that there is a greater risk of having pain in people living with HIV. [ABSTRACT FROM AUTHOR]

In mammals, procedures such as handling, restraint, or exposure to open spaces induces an increase in body temperature ([T.sub.b]). The increase in temperature shares some characteristics with pyrogen-induced fever and so is often called 'stress fever.' Birds also respond to acute handling with a stress fever, which may confound thermoregulatory studies that involve animal restraint. We have measured the [T.sub.b] responses of Pekin ducks on days when they were restrained and compared them to days when the birds remained unrestrained. Restraint induced a 0.5[degrees]C increase in [T.sub.b] that was sustained for the entire 8 h of restraint. To determine whether the restraint-induced increase in [T.sub.b] is mediated by prostaglandins (PGs) we compared the [T.sub.b] responses during restraint after intraperitoneal injection with saline to the responses during restraint after injection with diclofenac sodium (15 mg/kg). There was no difference in response, suggesting that restraint affects [T.sub.b] by a PG-independent mechanism. We also compared the [T.sub.b] response to intramuscular injection of lipopolysaccharide (LPS; 100 [micro]g/kg), a bacterial pyrogen, when the ducks were restrained or unrestrained. Despite [T.sub.b] being higher at the time of LPS injection when the ducks were restrained, the maximum temperature reached after LPS injection was higher, and the period that [T.sub.b] remained elevated was longer when the ducks were unrestrained. We conclude that restraint should be considered as a potential confounder in thermoregulatory studies in birds and presumably other species too. lipopolysaccharide; psychological stress; birds

Abstract: We characterized the time course of inflammatory cytokine release at the site of injury and in plasma after surgery on the rat tail. Anesthetized Sprague-Dawley rats had a 20 [...]

Information on avian fever is limited, and, in particular, very little is known about the mediators and modulators of the febrile response in birds. Therefore, in this study, the possible mediatory roles of nitric oxide (NO) and prostaglandins (PGs), together with a potential modulatory role for adrenocortical hormones in the generation of fever was investigated in conscious Pekin ducks. Their body temperatures were continuously measured by abdominally implanted temperature-sensitive data loggers. The febrile response induced by intramuscular injection of LPS at a dose of 100 [micro]g/kg was compared with and without inhibition of NO production by N-nitro-L-arginine methyl ester (L-NAME), inhibition of PG synthesis (by diclofenac), and elevation of circulating concentrations of dexamethasone and corticosterone (by exogenous administration). LPS administration induced a marked, monophasic fever with a rise in temperature of more than 1[degrees]C after 3-4 h. In the presence of L-NAME, diclofenac, and adrenocorticoids at doses that had no effect upon normal body temperature in afebrile ducks, there was a significant inhibition of the LPS-induced fever. In addition, during the febrile response, the blood concentration of corticosterone was significantly elevated (from a basal level of 73.6 [+ or -] 9.8 ng/ml to a peak level of 132.6 [+ or -] 16.5 ng/ml). The results strongly suggest that the synthesis of both NO and PGs is a vital step in the generation of fever in birds and that the magnitude of the response is subject to modulation by adrenocorticoids. avian fever; N-nitro-L-arginine methyl ester; pyrogen

Body temperature, behavior, and plasma cortisol changes induced by chronic infusion of Staphylococcus aureus in goats. Am J Physiol Regul Integr Comp Physiol 287: R863-R869, 2004. First published June 24. 2004; 10.1152/ajpregu.00064.2004.--Most experimentally induced fevers are acute, usually lasting ~6-12 h, and thus do not mimic chronic natural fevers, which can extend over several days or more. To produce a model of chronic natural fever, we infused eight goats (Capra hircus) intravenously with 2 ml of 2 X [10.sup.11] cell walls of Staphylococcus aureus (S. aureus) for 6 days using osmotic infusion pumps (10 [micro]l/h) while measuring changes in body temperature, behavior, and plasma cortisol concentration. Seven control animals were infused with sterile saline. Abdominal temperaturesensitive data loggers and osmotic infusion pumps were implanted under halothane anesthesia. To compare our new model with existing models of experimental fever, we also administered 2-ml bolus intravenous injections of 2 x [10.sup.11] S. aureus cell walls, 0.1 [micro]g/kg lipopolysaccharide (Escherichia coil, serotype 0111:B4), and sterile saline in random order to six other goats. Bolus injection of lipopolysaccharide and S. aureus induced typical acute phase responses, characterized by fevers lasting ~6 h, sickness behavior, and increased plasma cortisol concentration. Infusion of S. aureus evoked prolonged fevers, which lasted for ~3 days, starting on day 4 of infusion (ANOVA, P < 0.05), and did not disrupt the normal circadian rhythm of body temperature. However, pyrogen infusion did not cause plasma cortisol concentration to rise (ANOVA, P > 0.05) or the expression of sickness behavior. In conclusion, infusion of S. aureus produced a lever response resembling that of sustained natural fevers but did not elicit the cortisol and behavioral responses that often are described clinically and during short-term experimental fevers. osmotic infusion pumps; lipopolysaccharide; circadian rhythm

Background: People living with HIV (PLWH) frequently experience pain. Following calls to analyse individual-level data in addition to group-level data in pain studies, we compared individual and group-level changes in pain prevalence, intensity and number of pain sites over 48 weeks in a large cohort of PLWH. This is the largest ever cohort study of pain in PLWH, and is the first to report pain at the level of the individual.Methods: Participants included all participants with complete pain records from a randomized clinical trial (RCT) for the treatment of HIV (n = 787/1053). At weeks 0, 12, 24, 36 and 48 we assessed participants' pain in the last week; presence of pain, and if present, the intensity and locations of the pain. We used standard averaging methods to describe data at the group level, and unique graphical reporting methods to analyse data at the level of the individual.Results: Group-level data demonstrated a trend for pain prevalence to decline over time (19% week 0, 12% week 48). Worst pain intensity remained stable (median between 4/10 and 5/10), as did the number (median = 1) and common sites of pain across the 48 weeks. In contrast, individual-level data demonstrated high intra-individual variability with regards to the presence of pain, and the intensity and location of the pain.Conclusions: While our group-level data were similar to previous longitudinal studies, an apparent reduction in pain over 48 weeks, the individual-level data showed large variability within individuals in that same time frame.Significance: This graphical analysis highlights the high variability in pain (pain prevalence, intensity and body sites) across time in people living with HIV, and how presenting averaged data hides this important variability. Our data support the reporting of individual-level data in human experimental and observational studies. [ABSTRACT FROM AUTHOR]