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The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. These NK cells were hyperresponsive, with increased CCL4 production and expression of CD107a when co-cultured with human leukocyte antigen null target cells. Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16-binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves. Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.
Learn More >Opioid use for treatment of persistent pain has increased dramatically over the past two decades, but it has not resulted in improved pain management outcomes. To understand the molecular mechanisms of opioids, molecular signatures that arise from opioid exposure are often sought after, using various analytical methods. In this study, we performed proteomics, and multiglycomics via sequential analysis of polysialic acids, glycosaminoglycans, N-glycans and O-glycans, using the same cerebral spinal fluid (CSF) sample from patients that had long-term (>2 years), intrathecal morphine or baclofen administered via an indwelling pump. Proteomics and N-glycomics signatures between the two treatment groups were highly conserved, while significant differences were observed in polysialic acid, heparan sulfate glycosaminoglycan and O-glycan profiles between the two treatment groups. This represents the first study to investigate the potential relationships between diverse CSF conjugated glycans and long-term intrathecal drug exposure. The unique changes, observed by a sequential analytical workflow, reflect previously undescribed molecular effects of opioid administration and pain management.
Learn More >We aimed to adopt a multidimensional approach and investigate the interconnections between biomarkers (cytokines, matrix metalloproteinases, and cortisol) and psychosocial aspects considering pain acceptance, the individual construct of pain perception in terms of blood inflammation biomarkers, anxiety, self-efficacy, and functional performance and to define the quality of life (QoL) in women with rheumatoid arthritis (RA).
Learn More >To investigate the analgesic effects of vibro-acupuncture (VA), a novel acuvibrator was developed. Objectives: To compare the analgesic effects of VA with those of manual acupuncture (MA) and placebo acupuncture (PA) on subjects with normal sensory perception (Study I), experimentally induced acute pain (Study II), and clinical chronic pain (Study III).
Learn More >Studies comparing different drug treatments for chronic neuropathic pain (NP) are very limited. We, therefore, examined 4 recommended treatments, namely, antidepressants (duloxetine, venlafaxine, and tricyclic antidepressants), antiepileptics (gabapentine and pregabalin), weak opioids, and strong opioids, among patients with NP evaluated before first visit in a tertiary pain treatment centre and 6 months later. Patients with both a clinical diagnosis of NP and a DN4 score >=3/7 were selected from patients enrolled in the Quebec Pain Registry. Each participant was assigned an inverse weighting of the probability of receiving any NP treatment, taking into account their age, sex, baseline pain intensity, pain duration, pain catastrophizing tendency, education level, employment, and comedications at 6-month follow-up (M6). Patients were considered as improved if they presented at least a 30% reduction on average pain intensity at M6 compared with baseline. A total of 944 patients completed both baseline and M6 evaluations. Overall, 23.0% of patients were significantly improved for pain intensity at M6. There was no significant difference in proportions patients taking or not antidepressants, gabapentinoids, or weak opioids. Among patients taking strong opioids (N = 288), 13.9% (N = 40/288) were improved vs 27.0% (177/656) of those who were not on opioids (P < 0.004). Inverse probability of treatment weighting confirmed that the proportion of patients who improved was significantly lower among those taking strong opioids compared with those who did not (P < 0.001). In conclusion, long-term use of strong opioids is a treatment suited for a limited proportion of patients with chronic NP.
Learn More >Despite previous reports on cerebral structures and functional connectivity in patients with myofascial pain (MFP), it is not clear whether alterations in neurovascular coupling occur in these patients.
Learn More >Risk-factor identification related to chronic opioid use after surgery may facilitate interventions mitigating postoperative opioid consumption. We evaluated the relationship between opioid use preceding total hip arthroplasty (THA) and total knee arthroplasty (TKA), and chronic use postoperatively, and the risk of chronic opioid use after total joint arthroplasty.
Learn More >Research suggests that endogenous opioids play a key role in the creation and maintenance of attachment bonds. Opioids acting at the μ-opioid receptor mediate reward and analgesia and are thus thought to underlie feelings of comfort and warmth experienced in the presence of close others. Disruption of μ-opioidergic activity increases separation distress in animals, suggesting that low opioid states may contribute to social pain. Accordingly, a functional μ-opioid receptor (OPRM1) polymorphism (C77G in primates, A118G in humans) affecting opioidergic signaling has been associated with separation distress and attachment behavior in nonhuman primates, and social pain sensitivity in humans. However, no research has examined the effects of this polymorphism on socioemotional experience, and specifically felt security, in daily interactions between romantic partners. Using an event-contingent recording method, members of 92 cohabiting romantic couples reported their felt security and quarrelsome behavior in daily interactions with each other for 20 days. Consistent with prior work, findings suggested that, relative to AA homozygotes, G allele carriers were more sensitive to their partners' self-reported quarrelsome behaviors (e.g., criticism), showing a greater decline in felt security when their partners reported higher quarrelsome behavior than usual. This is the first study to link variation in OPRM1 with felt security toward romantic partners in everyday social interactions. More generally, this research supports the theory that the attachment system incorporated evolutionarily primitive pain-regulating opioidergic pathways. We also discuss implications of this work for understanding of differential vulnerability to health risks posed by social stress.
Learn More >Neuropathic pain is a debilitating consequence of spinal cord injury. Ecological momentary assessment can be a valuable research tool for understanding temporal fluctuations in neuropathic pain and designing effective management strategies. The objectives of this study were to (a) describe strategies necessary to adapt ecological momentary assessment to measure neuropathic pain in adults with spinal cord injury, and (b) explore participant perceptions of using ecological momentary assessment to measure pain sensations. End-users with spinal cord injury provided input to guide development of an ecological momentary assessment protocol. Six adults with spinal cord injury (ages 27-50 years, = 39.33 ± 8.24) engaged in the six-day protocol and completed six daily neuropathic pain assessments. Upon finishing participants completed a semi-structured interview regarding their protocol experiences. A qualitative content analysis was used to analyze the interview data. Participants reported that this specific ecological momentary assessment protocol was unobtrusive to their daily routines, and effectively captured their neuropathic pain sensations. However, participants experienced increased neuropathic pain due to the repeated nature of assessments. Ecological momentary assessment can capture the dynamic nature of neuropathic pain experienced by persons with spinal cord injury. However, caution should be taken when designing intensive pain-related protocols to minimize pain exacerbation.IMPLICATIONS FOR REHABILITATIONNeuropathic pain affects up to 75% of people with spinal cord injury and is one of the most frequently occurring, debilitating forms of pain.Appropriate and feasible pain data collection methods are necessary to acquire a better understanding of how neuropathic pain manifests in people with spinal cord injury.Implementing ecological momentary assessment in a rehabilitation setting may help facilitate the monitoring of neuropathic pain for both rehabilitation professionals and persons with SCI.Using ecological momentary assessment may lead to a better understanding of individual temporal patterns of neuropathic pain that could inform the design of tailored neuropathic pain management techniques.
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