Pain

Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine whether a patient should receive permanent SCS implant, its evidence base is limited. We aimed to establish the clinical utility, diagnostic accuracy, and cost-effectiveness of an SCS screening trial. A multicentre single-blind, parallel two-group randomised controlled superiority trial was undertaken at three centres in United Kingdom. Patients were randomised 1:1 to either SCS screening trial strategy (TG) or no trial screening strategy (NTG)...

Low back pain (LBP) is a leading cause of work disability. While absent from work, workers with LBP may receive income support from a system such as workers' compensation or social security. This study examines how and in what contexts income support systems impact the healthcare quality for people with work disability and LBP and their functional capacity. We performed a realist review. Five initial theories about the relationship between income support systems and outcomes were developed, tested, and refined by acquiring and synthesising academic literature from purposive and iterative electronic database searching...

Currently, opioids targeting mu-opioid receptors (MOR) are the most potent drugs for acute and cancer pain. However, opioids produce adverse side effects such as constipation, respiratory depression, or addiction potential. We recently developed (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), a compound that does not evoke central or intestinal side effects due to its selective activation of MOR at low pH in peripheral injured tissues. While we demonstrated that NFEPP effectively abolishes injury-induced pain, hyperalgesia and allodynia in rodents, the efficacy of NFEPP in non-evoked ongoing pain remains to be established...

It is unclear whether a diagnosis of chronic pain is associated with an increase or decrease in the placebo response. The aim of this study was to use an experimental placebo conditioning paradigm to test if expectancy for pain relief impacts on acute pain perception in individuals with a chronic pain diagnosis of osteoarthritis (OA) or fibromyalgia (FM), compared to healthy individuals (HI). An inert cream was applied to the dominant forearm of participants (60 OA, 79 FM and 98 HI), randomly assigned to either a placebo or control group...

Next generation transcriptomics in combination with imaging-based approaches have emerged as powerful tools for the characterization of dorsal root ganglion (DRG) neuronal subpopulations. The mouse DRG has been well-characterized by many independently conducted studies with convergent findings, but few studies have directly compared expression of population markers between mouse and human. This is important because of our increasing reliance on the mouse as a preclinical model for translational studies. While calcitonin gene-related peptide (CGRP) and P2X purinergic ion channel type 3 receptor (P2X3R) have been used to define peptidergic and non-peptidergic nociceptor subpopulations, respectively, in mouse DRG, these populations may be different in other species...

Pain-related disability is a multi-faceted construct that refers to the impact of pain on an individual's capacity to fulfill their self-defined and social roles. This research examined the relationship between clinical, psychological and pain sensitivity factors and pain-related disability among adults with chronic temporomandibular disorder (TMD). We analyzed data from a cross-sectional community-based sample of 1088 men and women with chronic TMD. We first constructed and tested a measure of pain-related disability (i...

Knee osteoarthritis (OA) is a heterogeneous disease, and identification of its subgroups/phenotypes can improve patient treatment and drug development. We aimed to identify homogeneous OA subgroups/phenotypes using pain development over time; to understand the interplay between pain and functional limitation in time course, and to investigate subgroups' responses to available pharmacological and surgical treatments. We used group-based trajectory modelling to identify pain trajectories in the phase-three VIDEO trial (n=474, three-year follow-up) and also in the Osteoarthritis Initiative cohort study (n=4796, nine-year follow-up)...

Correct communication between immune cells and peripheral neurons is crucial for the protection of our bodies. Its breakdown is observed in many common, often painful conditions, including arthritis, neuropathies and inflammatory bowel or bladder disease. Here, we have characterised the immune response in a mouse model of neuropathic pain using flow cytometry and cell-type specific RNA sequencing (RNA-seq). We found few striking sex differences, but a very persistent inflammatory response, with increased numbers of monocytes and macrophages up to 3½ months after the initial injury...

Luminal distention and abdominal pain are major clinical hallmarks of obstructive bowel disorders and functional bowel disorders linked to gut dysbiosis. Our recent studies found that chronic lumen distention increased visceral sensitivity and decreased abundance of gut commensal Lactobacillus reuteri in a rodent model of partial colon obstruction (OB). To establish causation, we performed precision microbial therapy to assess whether recolonization of L. reuteri prevents visceral hypersensitivity in lumen distention, and if so, to identify the gut-microbiota mechanism...

Acute pain that persists for a few days is associated with a reduction in patients' quality of life. Orofacial persistent pain promotes psychological disorders such as anxiety, impairs daily essential activities such as eating, and results in decreased social interaction. Here, we investigated whether rats subjected to orofacial formalin injection or intraoral incision surgery display persistent facial heat hyperalgesia, ongoing pain, anxiety-like behavior and changes in ultrasonic vocalization. Orofacial formalin injection or intraoral incision caused facial heat hyperalgesia for 3 days compared to saline-injected and sham animals...

Aerobic exercise is believed to be an effective chronic low back pain (CLBP) intervention, although its mechanisms remain largely untested. This study evaluated whether endogenous opioid (EO) mechanisms contributed to the analgesic effects of an aerobic exercise intervention for CLBP. Individuals with CLBP were randomized to a 6-week, 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 44). Before and after the intervention, participants underwent separate laboratory sessions to assess responses to evoked heat pain after receiving saline placebo or i...

Bone cancer-induced pain (BCP) is a challenging clinical problem because traditional therapies are often only partially effective. Annexin A3 (ANXA3) is highly expressed in microglia in the spinal cord, and its expression is upregulated during BCP. However, the roles of microglial ANXA3 in the development and maintenance of BCP and the underlying molecular mechanisms remain unclear. This study was performed on male mice using a metastatic lung BCP model. Adeno-associated virus shANXA3 (AAV-shANXA3) was injected intrathecally 14 days before and 7 days after bone cancer induction, and relevant pain behaviors were assessed by measuring the paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL), and spontaneous hindlimb lifting...

Recent meta-analyses have shown MBIs to be effective for chronic pain, but no pooled estimates of the effect of MBIs on acute pain are available. This meta-analysis was conducted to fill that gap. A literature search was conducted in four databases. Articles were eligible if they reported on randomized controlled trials of MBIs for people with acute pain and included one of the following outcomes: pain severity, pain threshold, pain tolerance or pain-related distress. Two authors independently extracted the data, assessed risk of bias and provided GRADE ratings...

The presence and magnitude of placebo responses is important for the outcome in clinical trials of analgesics. This explorative study aimed at identifying patients and trial specific factors with impact on this response in randomized, controlled, cross-over trials in peripheral neuropathic pain. Data were derived from 7 trials and included observations on pin-prick hyperalgesia, allodynia, and pain on repetitive stimulation. The studies were all performed by the same collaboration group in Denmark. Pain was rated daily using numeric 0-10 point rating scales (NRS) and placebo response was calculated as the difference in weekly average or median NRS from baseline to the last week of treatment...

Besides neuraxial analgesia, non-pharmacological methods are also proposed to help women coping with pain during labor. We aimed to identify the individual and organizational factors associated with the use of non-pharmacological analgesia for labor pain management. Women who attempted vaginal delivery with labor analgesia were selected among participants included in the 2016 National Perinatal Survey, a population-based cross-sectional study. Labor analgesia was studied as neuraxial analgesia alone, non-pharmacological analgesia alone, and neuraxial and non-pharmacological analgesia combined...

Musculoskeletal disorders such as knee osteoarthritis (OA) are the primary cause of chronic pain in older adults. Recommended self-management strategies for knee OA include staying physically active in the face of pain, but many patients avoid activities they are capable of doing. The overall purpose of this study was to examine the extent to which daily pain catastrophizing, a maladaptive coping strategy, could influence OA patients' physical activity and sedentary behavior. The current study utilized data from 143 older knee OA patients who completed electronic daily diaries for 22 days and wore an accelerometer to capture physical activity and sedentary behavior...

Hydromorphone is an alternative to morphine for Intrathecal Drug Delivery System (IDDS) to treat refractory cancer pain; however, there is not enough clinical evidence to prove it. In our study, 233 patients from 12 different pain management centers across China were enrolled, 121 and 112 in the intrathecal hydromorphone (ITHM) and intrathecal morphine (ITMO) groups, respectively. The primary outcome was the clinical success rate, which was defined as ratio of patients achieving ≥ 50% pain relief. The noninferiority margin (NIm) was defined as -0...

Children diagnosed with Christianson Syndrome (CS), a rare X-linked neurodevelopmental disorder characterized by intellectual disability, epilepsy, ataxia and mutism, also suffer from hyposensitivity to pain. This places them at risk of sustaining serious injuries that often go unattended. CS is caused by mutations in the alkali cation/proton exchanger SLC9A6/NHE6 that regulates recycling endosomal pH homeostasis and trafficking. Yet it remains unclear how defects in this transporter lead to altered somatosensory functions...

Musculoskeletal pain is the greatest cause of disability worldwide. Due to its increasing prevalence and burden, the importance of affordable treatments has been highlighted. Text messages interventions are accessible, low-cost and effective in promoting healthy behaviour and managing chronic diseases. However, little is known about their role in musculoskeletal pain. This systematic review was conducted to appraise the literature on the effects of text messages (as an intervention or a component of an intervention) compared to any control on pain and function in people with musculoskeletal pain (PROSPERO: CRD42018117371)...

PTSD symptoms and other negative psychosocial factors have been implicated in the transition from acute to persistent pain. Women (N = 375) who presented to an inner-city Emergency Department (ED) with complaints of acute pain were followed for 3 months. They completed a comprehensive battery of questionnaires at an initial visit, and provided ratings of pain intensity at the site of pain presented in the ED during 3 monthly phone calls. Latent class growth analyses were used to detect possible trajectories of change in pain intensity from initial visit to 3 months later...