Animal models of chemotherapy-induced peripheral neuropathy:a machine-assisted systematic review and meta-analysis

<div><p>We report a systematic review and meta-analysis of research using animal models of chemotherapy-induced peripheral neuropathy (CIPN). We systematically searched 5 online databases in September 2012 and updated the search in November 2015 using machine learning and text mining to reduce the screening for inclusion workload and improve accuracy. For each comparison, we calculated a standardised mean difference (SMD) effect size, and then combined effects in a random-effects meta-analysis. We assessed the impact of study design factors and reporting of measures to reduce risks of bias. We present power analyses for the most frequently reported behavioural tests; 337 publications were included. Most studies (84%) used male animals only. The most frequently reported outcome measure was evoked limb withdrawal in response to mechanical monofilaments. There was modest reporting of measures to reduce risks of bias. The number of animals required to obtain 80% power with a significance level of 0.05 varied substantially across behavioural tests. In this comprehensive summary of the use of animal models of CIPN, we have identified areas in which the value of preclinical CIPN studies might be increased. Using both sexes of animals in the modelling of CIPN, ensuring that outcome measures align with those most relevant in the clinic, and the animal’s pain contextualised ethology will likely improve external validity. Measures to reduce risk of bias should be employed to increase the internal validity of studies. Different outcome measures have different statistical power, and this can refine our approaches in the modelling of CIPN.</p></div

Deliverable report on 2.2b. Protocols for measuring disturbance of circadian rhythm and cognitive function in pain models

<p>Deliverable report 2.2b - Protocols for measuring disturbance of circadian rhythm and cognitive function in pain models.  Published by Workpackage 2 of project Europain.</p> <p>The EuroPain project has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115007, resources for which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/20072013) and EFPIA companies’ in kind contribution.This is a unique public-private partnership designed by the European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA). It is a pan-European collaboration that brings together large biopharmaceutical companies, small- and medium-sized enterprises (SMEs), patient organisations, academia, hospitals and public authorities.</p

Short-term effect of acute and repeated urinary bladder inflammation on thigmotactic behaviour in the laboratory rat : [v1; ref status: awaiting peer review, http://f1000r.es/56e] - See more at: http://f1000research.com/articles/4-109/v1#sthash.T4hJEMI2.dpuf

Grant information: This work was primarily funded by an MRC CASE award in conjunction with Pfizer to the London Pain Consortium (Wellcome Trust Strategic Award 083259). The manuscript was written under joint-funding from the Europain Collaboration, which has received support from the Innovative Medicines Initiative Joint Undertaking, under grant agreement AG2013/3347, and NC3Rs (P41508).Non peer reviewedPublisher PD

Reduced intraepidermal nerve fibre density, glial activation, and sensory changes in HIV type-1 Tat-expressing female mice: involvement of Tat during early stages of HIV-associated painful sensory neuropathy

Abstract. Introduction:. HIV infection is associated with chronic pain states, including sensory neuropathy, which affects greater than 40% of patients. Objectives and Methods:. To determine the impact of HIV-Tat induction on nociceptive behaviour in female mice conditionally expressing HIV Tat1-86 protein through a doxycycline (DOX)-driven glial fibrillary acidic protein promoter, intraepidermal nerve fibre density and immune cell activation in the dorsal root ganglion (DRG) and spinal cord were assessed by immunohistochemistry. Mice were assessed for mechanical and thermal sensitivity for 9 weeks using von-Frey and Hargreaves tests. Results:. Intraepidermal nerve fibre density was significantly reduced after 6 weeks of Tat induction, similar to sensory neuropathy seen in clinical HIV infection. Tat induction through DOX caused a significant reduction in paw withdrawal thresholds in a time-dependent manner starting the 4th week after Tat induction. No changes in paw withdrawal latencies were seen in Tat(−) control mice lacking the tat transgene. Although reductions in paw withdrawal thresholds increased throughout the study, no significant change in spontaneous motor activity was observed. Spinal cord (cervical and lumbar), DRG, and hind paw skin were collected at 8 days and 6 weeks after Tat induction. HIV-Tat mRNA expression was significantly increased in lumbar DRG and skin samples 8 days after DOX treatment. Tat induced a significant increase in the number of Iba-1 positive cells at 6 weeks, but not after 8 days, of exposure. No differences in glial fibrillary acidic protein immunoreactivity were observed. Conclusion:. These results suggest that Tat protein contributes to painful HIV-related sensory neuropathy during the initial stages of the pathogenesis

Hydrogen peroxide is a novel mediator of inflammatory hyperalgesia, acting via transient receptor potential vanilloid 1-dependent and independent mechanisms

Inflammatory diseases associated with pain are often difficult to treat in the clinic due to insufficient understanding of the nociceptive pathways involved. Recently, there has been considerable interest in the role of reactive oxygen species (ROS) in inflammatory disease, but little is known of the role of hydrogen peroxide (H(2)O(2)) in hyperalgesia. In the present study, intraplantar injection of H(2)O(2)-induced a significant dose- and time-dependent mechanical and thermal hyperalgesia in the mouse hind paw, with increased c-fos activity observed in the dorsal horn of the spinal cord. H(2)O(2) also induced significant nociceptive behavior Such as increased paw licking and decreased body liftings. H(2)O(2) levels were significantly raised in the carrageenan-induced hind paw inflammation model, showing that this ROS is produced endogenously in a model of inflammation. Moreover, superoxide dismutase and catalase significantly reduced carrageenan-induced mechanical and thermal hyperalgesia, providing evidence of a functionally significant endogenous role. Thermal, but not mechanical, hyperalgesia in response to H(2)O(2) (i.pl.) Was longer lasting in TRPV1 wild type mice compared to TRPV1 knockouts. It is unlikely that downstream lipid peroxidation was increased by H(2)O(2). In conclusion, we demonstrate a notable effect of H(2)O(2) in mediating inflammatory hyperalgesia, thus highlighting H(2)O(2) removal as a novel therapeutic target for anti-hyperalgesic drugs in the clinic. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.Arthritis Research CampaignArthritis Research CampaignBBSRCBBSRCBPSBPSHEFCEHEFCEKTNKTNMRCMRCSFCSF