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A consistent line of investigation proposes fibromyalgia as a dysautonomia-associated neuropathic pain syndrome. Comorbid anxiety or depression amplifies fibromyalgia symptoms. The recent recognition of small fiber neuropathy in fibromyalgia patients supports the neuropathic nature of the illness. Corneal confocal microscopy accurately identifies small nerve fiber pathology. The newly developed Small-Fiber Symptom Survey captures the spectrum of small fiber neuropathy symptoms. We aimed to correlate corneal nerve density with different fibromyalgia disease severity questionnaires including the Small-Fiber Symptom Survey. We defined the possible confounding role of comorbid anxiety or depression severity in the clinical-pathological association.
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 >Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to reduce motor symptoms of Parkinson's disease (PD). The effects of DBS on various nonmotor symptoms often differ from patient to patient. The factors that determine whether or not a patient will respond to treatment have not been elucidated. Here, the authors evaluated sex differences in pain relief after DBS for PD.
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 >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.
Learn More >Neuropathic pain is associated with poor health-related quality of life (HRQL) in pain conditions other than sickle cell disease (SCD); this relationship in SCD is unknown. We investigated this relationship and hypothesized neuropathic pain is associated with poor HRQL in adolescents with SCD.
Learn More >Men and women can exhibit different pain sensitivities and many chronic pain conditions are more prevalent in one sex. Although there is evidence of sex differences in the brain, it is not known whether there are sex differences in the organization of large-scale functional brain networks in chronic pain. Here, we used graph theory with modular analysis and machine-learning of resting-state (RS)-fMRI data from 220 participants; 155 healthy controls and 65 individuals with chronic low back pain due to ankylosing spondylitis (AS), a form of arthritis.We found an extensive overlap in the graph partitions with the major brain intrinsic systems (i.e., default mode, central, visual and sensorimotor modules), but also sex-specific network topological characteristics in healthy people and those with chronic pain. People with chronic pain exhibited higher cross-network connectivity, and sex-specific nodal graph properties changes (i.e., Hubs disruption), some of which were associated with the severity of the chronic pain condition. Females exhibited atypically higher functional segregation in the mid- and subgenual cingulate cortex and lower connectivity in the network with the default mode and fronto-parietal modules; whereas males exhibited stronger connectivity with the sensorimotor module. Classification models on nodal graph metrics could classify an individuals' sex and whether they have chronic pain with high accuracies (77-92%). These findings highlight the organizational abnormalities of RS-brain networks in people with chronic pain and provide a framework to consider sex-specific pain therapeutics.
Learn More >Pain is a common non-motor symptom in patients with Parkinson's disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into three groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory (BPI) and McGill pain questionnaire (MPQ), PDQ-8 quality of life score, MDS-UPDRS scores, and non-motor symptoms). 159 non-demented PD patients (disease duration 10.2±7.6 years) and 37 healthy controls were recruited in four centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain's BPI and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression and anxiety measures. Moderate intra- and inter-rater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.
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