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Persistent postpartum pelvic pain affects one in six women, and its source is often unexplained in the absence of obvious clinical findings. Musculoskeletal injuries during childbirth are common and can be detected using MRI or US; however, pelvic imaging is not standard of care in evaluating women with persistent pain. We hypothesize that clinical symptoms in women with unexplained persistent postpartum pelvic pain will correlate with musculoskeletal abnormalities identified on MRI in > 50% of cases.
Learn More >Substantial investment has gone into research on the efficacy and effectiveness of pharmaceutical and nonpharmacologic interventions for chronic pain. However, synthesizing this extensive literature is challenging because of differences in the outcome measures used in studies of similar or competing interventions. The absence of a common metric makes it difficult to replicate findings, pool data from multiple studies, resolve conflicting conclusions, or reach consensus when interpreting findings.
Learn More >Objectives Physical activity is essential for long-term chronic pain management, yet individuals struggle to participate. Exercise professionals, including fitness instructors, and personal trainers, are preferred delivery agents for education and instruction on chronic pain, physical activity, and strategies to use adherence-promoting behavioral skills. However, exercise professionals receive no relevant training during certification or continuing education opportunities to effectively support their participants living with chronic pain. Based on the ORBIT model for early pre-efficacy phases of development and testing of new behavioral treatments, the present Phase IIa proof-of-concept study was conducted. The purpose was to examine the impacts of a newly developed chronic pain and physical activity training workshop on psychosocial outcomes among exercise professionals. Outcomes included knowledge and attitudes regarding chronic pain, attitudes and beliefs about the relationship between pain and impairment, and self-efficacy to educate and instruct participants with chronic pain. Methods Forty-eight exercise professionals (Mage=44.4±11.0 years) participated in a three-hour, in-person workshop that was offered at one of four different locations. Participants completed pre- and post-workshop outcome assessment surveys. Results Mixed MANOVA results comparing time (pre- versus post-workshop) by workshop location (sites 1 to 4) illustrated a significant within-subjects time effect (p<0.001). All outcomes significantly improved from pre- to post-workshop (p's<0.001), demonstrating large effect sizes (partial eta-squared values ranging from 0.45 to 0.59). Conclusions Findings offer early phase preliminary support for the effectiveness of the chronic pain and physical activity training workshop for exercise professionals. Based on ORBIT model recommendations, findings warrant future phased testing via a pilot randomized clinical trial as well as testing for impacts that trained professionals have on activity adherence among their clients living with chronic pain. Eventual workshop adoption by exercise professional certification organizations would ensure widespread and sustainable access to qualified exercise professionals to help individuals engage in physical activity. By increasing the capacity of available exercise professionals to deliver effective support, active individuals could better manage their chronic pain and live well.
Learn More >To assess the relative safety of oral tapentadol PR and other opioid analgesics for moderate or severe chronic pain in adults, we conducted a systematic review and network meta-analysis (NMA). A systematic review was conducted to identify randomized controlled trials (RCTs) and randomised withdrawal trials of tapentadol with other WHO stage II and III opioid analgesics in patients with moderate or severe chronic pain. Searches were conducted in MEDLINE, EMBASE, PubMed, Cochrane databases and trial registries. Feasibility assessment evaluated the trials' suitability for NMA. Outcomes assessed were overall AEs, overall serious adverse events, constipation, nausea, dizziness, somnolence, headache, and discontinuation due to AEs. Randomized withdrawal trials were analysed separately to other RCTs. Searches conducted in April 2019 identified 16,604 records. Following screening and feasibility assessment, 29 RCTs and 19 randomized withdrawal trials were identified and included in the NMA.Consistent with existing research, evidence from RCTs suggested that tapentadol is associated with relatively lower odds of adverse events occurring than most active comparators. The withdrawal trial data were less clear, with higher uncertainty around the results, and results that appear to contradict the RCT evidence. There are a number of trial design factors that may be affecting these results. RCT evidence suggests that tapentadol can be a useful treatment option for patients suffering from chronic pain and in need of an opioid analgesic. Opioids should be prescribed by a qualified physician only after other analgesics have been considered, taking side effects and misuse risk into account.
Learn More >IBNtxA (3-iodobenzoyl naltrexamine) is a novel μ-opioid receptor (MOR) agonist which is structurally related to the MOR antagonist naltrexone. Recent studies suggest IBNtxA preferentially signals through truncated MOR splice variants, resulting in anti-nociception with reduced side effects, including no conditioned place preference (CPP) when tested at a single dose. IBNtxA represents an intriguing lead compound for preclinical drug development targeting truncated MOR splice variants, but further evaluation of its pharmacological profile is necessary. The purpose of this study was to independently verify the antinociceptive properties of IBNtxA and to examine more completely the rewarding properties and discriminative stimulus effects of IBNtxA, allowing broader assessment of IBNtxA as a candidate for further medications development. A dose of 3 mg/kg IBNtxA was equipotent to 10 mg/kg morphine in a hot-plate analgesia assay. In drug discrimination testing using mice trained to discriminate between 3 mg/kg IBNtxA and vehicle, the κ-agonist U-50488 fully substituted for IBNtxA. MOR agonist morphine, δ-agonist SNC162, NOP agonist SCH 221510, and MOR/NOP partial agonist buprenorphine each partially substituted for IBNtxA. IBNtxA up to 3 mg/kg did not produce a place preference in CPP. Pretreatment with 3 mg/kg IBNtxA but not 1 mg/kg IBNtxA attenuated acquisition of place preference for 10 mg/kg morphine. A dose of 3 mg/kg IBNtxA attenuated morphine-induced hyperlocomotion but did not alter naloxone-precipitated morphine withdrawal. Overall, IBNtxA has a complicated opioid receptor pharmacology . These results indicate that IBNtxA produces potent anti-nociception and has low abuse liability, likely driven by substantial κ agonist signaling effects.
Learn More >In addition to the risk of developing opioid use disorder (OUD), known side-effects of long-term opioid use include chronic inflammation and hyperalgesia, which may arise from immune responses induced following chronic opioid use. To investigate this hypothesis, blood samples were obtained from individuals with chronic back pain who were either chronically taking prescription opioids or had minimal recent opioid exposure. Patient samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) against hydrocodone- or oxycodone-hapten conjugates to assess the levels of antibodies present in the samples. While no specific response was seen in opioid-naïve subjects, we observed varying levels of anti-opioid IgM antibodies in the exposed subjects. In these subjects, antibody formation was found to be weakly correlated with current reported daily opioid dose. Other drugs of abuse found to elicit an immune response have been shown to generate advanced glycation end-products (AGEs) through reaction with glucose and subsequent modification of self-proteins. Investigations into this potential mechanism of anti-opioid antibody production identified reduced the formation of reactive intermediate species upon norhydrocodone reaction with glucose in comparison with nornicotine, thus identifying potentially important differences in hapten processing to yield the observed adaptive immune response.
Learn More >Irritable bowel syndrome is a functional gastrointestinal disorder with symptoms including abdominal pain associated with a change in stool form or frequency. The condition affects between 5% and 10% of otherwise healthy individuals at any one point in time and, in most people, runs a relapsing and remitting course. The best described risk factor is acute enteric infection, but irritable bowel syndrome is also more common in people with psychological comorbidity and in young adult women than in the rest of the general population. The pathophysiology of irritable bowel syndrome is incompletely understood, but it is well established that there is disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and altered CNS processing. Other less reproducible mechanisms might include genetic associations, alterations in gastrointestinal microbiota, and disturbances in mucosal and immune function. In most people, diagnosis can be made on the basis of clinical history with limited and judicious use of investigations, unless alarm symptoms such as weight loss or rectal bleeding are present, or there is a family history of inflammatory bowel disease or coeliac disease. Once the diagnosis is made, an empathetic approach is key and can improve quality of life and symptoms, and reduce health-care expenditure. The mainstays of treatment include patient education about the condition, dietary changes, soluble fibre, and antispasmodic drugs. Other treatments tend to be reserved for people with severe symptoms and include central neuromodulators, intestinal secretagogues, drugs acting on opioid or 5-HT receptors, or minimally absorbed antibiotics (all of which are selected according to predominant bowel habit), as well as psychological therapies. Increased understanding of the pathophysiology of irritable bowel syndrome in the past 10 years has led to a healthy pipeline of novel drugs in development.
Learn More >Evaluate the safety and efficacy of a single injection of STRO-3+ adult allogeneic mesenchymal precursor cells (MPCs) combined with hyaluronic acid (HA) in subjects with chronic low back pain (CLBP) associated with degenerative disc disease (DDD) through 36 months follow-up.
Learn More >Nitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia and for short duration analgesia in various clinical settings mostly in the form of a N2O/O2 50%-50% equimolar mixture (EMONO). Experimental studies have suggested that EMONO could also induce long lasting analgesic effects related to the blockade of NMDA receptors. We designed the first international multicenter proof of concept randomized, placebo-controlled study to assess the efficacy and safety of a one hour administration of EMONO or placebo (medical air) on three consecutive days up to one month after the last administration in patients with chronic peripheral neuropathic pain. A total of 240 patients were recruited in 22 centers in France and Germany and randomly assigned to one study group (120 per group). Average pain intensity (primary outcome), neuropathic pain characteristics (NPSI), patient global impression of change (PGIC), anxiety, depression and quality of life were systematically assessed before and after treatment. The changes in average pain intensity between baseline and seven days after the last administration were not significantly different between the two groups. However, evoked pain intensity (predefined secondary endpoint) and PGIC (exploratory endpoint), were significantly improved in the EMONO group and these effects were maintained up to four weeks after the last treatment administration. Mostly transient side effects were reported during the treatment administration. These encouraging results provide a basis for further investigation of the long term analgesic effects of EMONO in neuropathic pain patients.
Learn More >It currently remains unclear, why some patients with entrapment neuropathies develop neuropathic pain (neuP) whereas others have non-neuP, presumably of nociceptive character. Studying patients with carpal tunnel syndrome (CTS), this cross-sectional cohort study investigated changes in somatosensory structure and function as well as emotional wellbeing specific to the presence and severity of neuP.Patients with CTS (n=108) were subgrouped by the DN4 questionnaire into those without and with neuP. The latter group was further subdivided into mild and moderate/severe neuP using a pain visual analogue scale. N=32 participants served as healthy controls. All participants underwent a clinical examination, quantitative sensory testing (QST), electrodiagnostic testing (EDT) and skin biopsy to determine structural integrity of dermal and intraepidermal nerve fibres. Patients also completed questionnaires evaluating symptom severity and functional deficits, pain distribution, sleep quality and emotional wellbeing. The overall prevalence of neuP in patients with CTS was 80%, of which 63% had mild neuP. Symptom severity and functional deficits as well as somatosensory dysfunction were more pronounced with the presence and increasing severity of neuP. No difference was identified among patient groups for EDT and nerve fibre integrity on biopsies. The severity of neuP was accompanied by more pronounced deficits in emotional wellbeing and sleep quality. Intriguingly, extraterritorial spread of symptoms was more prevalent in patients with moderate/severe neuP, indicating the presence of central mechanisms. NeuP is common in patients with CTS and its severity is related to the extent of somatosensory dysfunction and a compromise of emotional wellbeing.
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