Curr Opin Pharmacol
December 2023
Translating promising preclinical pain relief data for novel molecules from drug discovery to positive clinical trial outcomes is challenging. The angiotensin II type 2 (AT) receptor is a clinically-validated target based upon positive proof-of-concept clinical trial data in patients with post-herpetic neuralgia. This trial was conducted because AT receptor antagonists evoked pain relief in rodent models of neuropathic pain.
View Article and Find Full Text PDFObjective: Thigmotaxis is an innate predator avoidance behaviour of rodents and is enhanced when animals are under stress. It is characterised by the preference of a rodent to seek shelter, rather than expose itself to the aversive open area. The behaviour has been proposed to be a measurable construct that can address the impact of pain on rodent behaviour.
View Article and Find Full Text PDFCochrane Database Syst Rev
December 2021
Background: Implanted spinal neuromodulation (SNMD) techniques are used in the treatment of refractory chronic pain. They involve the implantation of electrodes around the spinal cord (spinal cord stimulation (SCS)) or dorsal root ganglion (dorsal root ganglion stimulation (DRGS)), and a pulse generator unit under the skin. Electrical stimulation is then used with the aim of reducing pain intensity.
View Article and Find Full Text PDFBackground: Neuropathic pain negatively affects quality of life among people living with HIV (PLWH). This study examined the feasibility of conducting a full-scale randomized-controlled trial of online acceptance and commitment therapy ("ACT OPEN") for neuropathic pain in PLWH.
Methods: Using a parallel-groups design, thirty-eight participants were randomized to ACT OPEN or a waitlist control (2:1).
The extraction of data from the reports of primary studies, on which the results of systematic reviews depend, needs to be carried out accurately. To aid reliability, it is recommended that two researchers carry out data extraction independently. The extraction of statistical data from graphs in PDF files is particularly challenging, as the process is usually completely manual, and reviewers need sometimes to revert to holding a ruler against the page to read off values: an inherently time-consuming and error-prone process.
View Article and Find Full Text PDFPeople living with HIV represent a unique aging population, living with a chronic condition associated with significant pain. A number take high dose, long-term opioids to manage moderate to severe chronic pain, presenting specific risks. This article highlights the size and impact of this problem and outlines the service objectives and set up of a specialist clinic to manage people living with HIV on high dose opioids, alongside its successes and learning points.
View Article and Find Full Text PDFBackground: Gabapentin is commonly used to treat neuropathic pain (pain due to nerve damage). This review updates a review published in 2014, and previous reviews published in 2011, 2005 and 2000.
Objectives: To assess the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain in adults.
Cochrane Database Syst Rev
January 2017
Background: This review is an update of 'Topical capsaicin (high concentration) for chronic neuropathic pain in adults' last updated in Issue 2, 2013. Topical creams with capsaicin are used to treat peripheral neuropathic pain. Following application to the skin, capsaicin causes enhanced sensitivity, followed by a period with reduced sensitivity and, after repeated applications, persistent desensitisation.
View Article and Find Full Text PDFBurrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures.
View Article and Find Full Text PDFPLoS One
June 2017
HIV-associated sensory peripheral neuropathy (HIV-SN) afflicts approximately 50% of patients on antiretroviral therapy, and is associated with significant neuropathic pain. Simple accurate diagnostic instruments are required for clinical research and daily practice in both high- and low-resource setting. A 4-item clinical tool (CHANT: Clinical HIV-associated Neuropathy Tool) assessing symptoms (pain and numbness) and signs (ankle reflexes and vibration sense) was developed by selecting and combining the most accurate measurands from a deep phenotyping study of HIV positive people (Pain In Neuropathy Study-HIV-PINS).
View Article and Find Full Text PDFBurrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures.
View Article and Find Full Text PDFCochrane Database Syst Rev
October 2015
Background: Although often considered to be lacking adequate evidence, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the management of neuropathic pain. Previous surveys found 18% to 47% of affected people reported using NSAIDs specifically for their neuropathic pain, although possibly not in the United Kingdom (UK).
Objectives: To assess the analgesic efficacy of oral NSAIDs for chronic neuropathic pain in adults, when compared to placebo or another active intervention, and the adverse events associated with its use in clinical trials.
Unlabelled: We conducted a randomized, double-blind, placebo-controlled, crossover study at a single center in South Africa, to ascertain whether amitriptyline is an effective analgesic for painful HIV-associated sensory neuropathy of moderate to severe intensity in: i) antiretroviral drug naive individuals, and ii) antiretroviral drug users. 124 HIV-infected participants (antiretroviral drug naive = 62, antiretroviral drug users = 62) who met the study criteria for painful HIV-associated sensory neuropathy were randomized to once-daily oral amitriptyline (titrated to a median: interquartile range of 50: 25-50 mg) or placebo for six weeks, followed by a three-week washout period and subsequent treatment crossover. The primary outcome measure was change from baseline in worst pain intensity of the feet (measured by participant self-report using an 11-point numerical pain rating scale) after six weeks of treatment.
View Article and Find Full Text PDFBackground: 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.
Understanding the non-sensory components of the pain experience is crucial to developing effective treatments for pain conditions. Chronic pain is associated with increased incidence of anxio-depressive disorders, and patients often report feelings of vulnerability which can decrease quality of life. In animal models of pain, observation of behaviours such as thigmotaxis can be used to detect such affective disturbances by exploiting the influence of nociceptive stimuli on the innate behavioural conflict between exploration of a novel space and predator avoidance behaviour.
View Article and Find Full Text PDFUnlabelled: Peer-reviewed publications of randomized clinical trials (RCTs) are the primary means of disseminating research findings. "Spin" in RCT publications is misrepresentation of statistically nonsignificant research findings to suggest treatment benefit. Spin can influence the way readers interpret clinical trials and use the information to make decisions about treatments and medical policies.
View Article and Find Full Text PDFThe principal feature of injuries from World War 1 was musculoskeletal trauma and injury to peripheral nerves as a result of damage to the upper and lower limbs caused by gunshot wounds and fragments of artillery munitions. Amputation was used as a treatment in field hospitals to save lives; limb conservation was a secondary consideration. A century later, the principal feature of injuries to soldiers in today's wars in Iraq and Afghanistan is also musculoskeletal trauma and injury to the peripheral nerves caused by improvised explosive devices.
View Article and Find Full Text PDFThe objective of these studies was to assess the efficacy and safety of pregabalin in the treatment of human immunodeficiency virus (HIV)-associated neuropathic pain. Patients with HIV-associated distal sensory polyneuropathy (DSP) were randomized to treatment with flexible-dose pregabalin (150-600 mg/day) or placebo for 17 weeks in a single-blind, placebo lead-in, randomized, double-blind, parallel-group, placebo-controlled multinational trial. The primary efficacy outcome was the change in mean pain score on an 11-point numeric rating scale (NRS) from baseline to study endpoint.
View Article and Find Full Text PDFCochrane Database Syst Rev
April 2014
Background: This review is an update of a review published in 2011, itself a major update of previous reviews published in 2005 and 2000, investigating the effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage chronic neuropathic pain and fibromyalgia.
Objectives: To assess the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain and fibromyalgia.
Individuals infected with the HIV and taking certain antiretroviral drugs to suppress viral replication have a high prevalence of neuropathic pain that is not alleviated by analgesic/adjuvant drugs that are often efficacious for the relief of other types of neuropathic pain. There is therefore a great need for new analgesics to alleviate the pain of antiretroviral toxic neuropathy (ATN). Small-molecule angiotensin II type 2 receptor (AT2R) antagonists, with ≥1000-fold selectivity over the angiotensin II type 1 receptor, produced analgesia in the chronic constriction injury of the sciatic nerve rat model of peripheral nerve trauma.
View Article and Find Full Text PDFCochrane Database Syst Rev
November 2013
Background: Antiepileptic drugs have been used for treating different types of neuropathic pain, and sometimes fibromyalgia. Our understanding of quality standards in chronic pain trials has improved to include new sources of potential bias. Individual Cochrane reviews using these new standards have assessed individual antiepileptic drugs.
View Article and Find Full Text PDFVGF (nonacronymic) is a neuropeptide precursor that plays multiple roles in regulation of energy balance, reproduction, hippocampal synaptic plasticity, and pain. Data from a number of pain models showed significant up-regulation of VGF in sensory neurons. TLQP-21, one of the VGF-derived neuropeptides, has been shown to induce a hyperalgesic response when injected subcutaneously into the hind paw of mice.
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