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The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific CHRFAM7A gene and its 2bp deletion polymorphism (Δ2bp variant) encodes a structurally-deficient α7nAChRs that may impact the anti-inflammatory function. We studied 45 spinal cord injury (SCI) patients for up to six weeks post SCI to investigate the role of the Δ2bp variant on multiple circulating inflammatory mediators and two outcome measures (neuropathic pain and risk of pressure ulcers). The patient's SCI were classified as either severe or mild. Missing values were imputed. Overall genetic effect was conducted with independent sample t-test and corrected with false discovery rate (FDR). Univariate analysis and regression analysis were applied to evaluate the Δ2bp effects on temporal variation of inflammatory mediators post SCI and their interaction with outcome measures. In severe SCI, the Δ2bp carriers showed higher levels of circulating inflammatory mediators than the Δ2bp non-carriers in TNF-α (FDR = 9.6×10-4), IFN-γ (FDR = 1.3×10-3), IL-13 (FDR = 1.6×10-3), CCL11 (FDR = 2.1×10-3), IL-12p70 (FDR = 2.2×10-3), IL-8 (FDR = 2.2×10-3), CXCL10 (FDR = 3.1×10-3), CCL4 (FDR = 5.7×10-3), IL-12p40 (FDR = 7.1×10-3), IL-1b (FDR = 0.014), IL-15 (FDR = 0.024), and IL-2 (FDR = 0.037). IL-8 and CCL2 were negatively associated with days post injury (DPI) for the Δ2bp carriers (P = 2×10-7 and P = 2×10-8, respectively) and IL-5 was positively associated with DPI for the Δ2bp non-carriers (P = 0.015). Neuropathic pain was marginally positively associated with IL-13 for the Δ2bp carriers (P = 0.056). In mild SCI, the Δ2bp carriers had lower circulating levels of IL-15 (FDR = 0.04) than the Δ2bp non-carriers. Temporal variation of inflammatory mediators post SCI was not associated with the Δ2bp variant. For the mild SCI Δ2bp carriers, risk of pressure ulcers was positively associated with circulating levels of IFN-γ, CXCL10, and CCL4 and negatively associated with circulating levels of IL-12p70. These findings support an important role for the human-specific CHRFAM7A Δ2bp gene variant in modifying anti-inflammatory function of α7nAChRs following SCI.
Learn More >The bidirectional relationship between depression and chronic pain is well-recognized, but their clinical management remains challenging. Here we characterize the shared risk factors and outcomes for their comorbidity in the Australian Genetics of Depression cohort study ( = 13,839). Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health. Logistic regression models were used to examine the relationship between chronic pain and clinical and demographic factors. Cumulative linked logistic regressions assessed the effect of chronic pain on treatment response for 10 different antidepressants. Chronic pain was associated with an increased risk of depression (OR = 1.86 [1.37-2.54]), recent suicide attempt (OR = 1.88 [1.14-3.09]), higher use of tobacco (OR = 1.05 [1.02-1.09]) and misuse of painkillers (e.g., opioids; OR = 1.31 [1.06-1.62]). Participants with comorbid chronic pain and depression reported fewer functional benefits from antidepressant use and lower benefits from sertraline (OR = 0.75 [0.68-0.83]), escitalopram (OR = 0.75 [0.67-0.85]) and venlafaxine (OR = 0.78 [0.68-0.88]) when compared to participants without chronic pain. Furthermore, participants taking sertraline (OR = 0.45 [0.30-0.67]), escitalopram (OR = 0.45 [0.27-0.74]) and citalopram (OR = 0.32 [0.15-0.67]) specifically for chronic pain (among other indications) reported lower benefits compared to other participants taking these same medications but not for chronic pain. These findings reveal novel insights into the complex relationship between chronic pain and depression. Treatment response analyses indicate differential effectiveness between particular antidepressants and poorer functional outcomes for these comorbid conditions. Further examination is warranted in targeted interventional clinical trials, which also include neuroimaging genetics and pharmacogenomics protocols. This work will advance the delineation of disease risk indicators and novel aetiological pathways for therapeutic intervention in comorbid pain and depression as well as other psychiatric comorbidities.
Learn More >Long-term opioid therapy was prescribed with increasing frequency over the past decade. However, factors surrounding long-term use of opioids in older adults remains poorly understood, probably because older people are not at the center stage of the national opioid crisis.
Learn More >Chronic migraine is a difficult disease to diagnose, and its pathophysiology remains undefined. Its symptoms affect the quality of life and daily living tasks of the affected person, leading to momentary disability. This is a pilot, randomized, controlled, double-blind clinical trial study with female patients between 18 and 65 years old with chronic migraine. The patients underwent twelve mindfulness sessions paired with anodal transcranial direct-current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC), with current intensity of 2 mA applied for 20 min, three times a week for 4 weeks. In addition, 20 min of mindfulness home practices were performed by guided meditation audio files. A total of 30 participants were evaluated after the treatment, and these were subdivided into two groups-active tDCS and sham tDCS, both set to mindfulness practice. The FFMQ-BR (Five Facet of Mindfulness Questionnaire), MIDAS (Migraine Disability Assessment), and HIT-6 (Headache Impact Test) questionnaires were used to evaluate the outcomes. After the treatment, the active mindfulness and tDCS group showed better results in all outcomes. The sham group also showed improvements, but with smaller effect sizes compared to the active group. The only significant difference in the intergroup analysis was the outcome evaluated by HIT-6 in the post treatment result. Our results provide the first therapeutic evidence of mindfulness practices associated with left DLPFC anodal tDCS with a consequent increase in the level of full attention and analgesic benefits in the clinical symptoms of patients with chronic migraine.
Learn More >Group medical visits (GMVs) for patients with chronic pain are becoming more accessible and have been shown to be successful in furthering patient education on multidisciplinary, nonopioid interventions. Unfortunately, evidence suggests that many group visit models lack sustainability due to recruitment issues and retention rates. Additionally, most of the studies surrounding GMVs are located in primarily urban health centers, potentially limiting their generalizability. This study aims to identify patient interest in and barriers to GMVs for chronic pain and to explore how chronic pain impacts daily lives for GMV content optimization in a nonurban population. Nineteen participants age 18 to 65 years participated in semistructured phone interviews to generate a thematic analysis. Participants received their care from family practitioners at a suburban multiclinic academic medical group and were being prescribed at least 50 morphine milligram equivalents (MME) at the time of recruitment. Analysis generated two themes: (1) and Findings support significant patient interest in group medical visits for chronic pain, but careful planning is necessary to address patient needs, expectations, and barriers in order to ensure GMV sustainability.
Learn More >The fear-avoidance model provides an explanation for the development of chronic pain, including the role of perception (i.e. pain catastrophism) as an explanatory variable. Recent research has shown that the relationship between pain catastrophism and avoidance is influenced in turn by different psychological and contextual variables, highlighting the affective-motivational ones. From this perspective, the Goal Pursuit Questionnaire (GPQ) was developed to measure the preference for hedonic goals (mood-management or pain-avoidance goals) over achievement goals in musculoskeletal pain patients. Recently, the Spanish version of the GPQ in fibromyalgia patients has been validated. Our aim has been to adapt the Spanish version of GPQ from pain to fatigue symptoms and to validate this new questionnaire (GPQ-F) in fibromyalgia. Despite the recognition of fibromyalgia as a complex disorder and the need for a differential study of its symptoms, fatigue, despite its high prevalence and limiting nature, remains the forgotten symptom. We conducted a cross-sectional study with 231 women with fibromyalgia. Previously, we adapted the Spanish GPQ for fatigue symptoms with three sub-studies (group structured interview, self-administration questionnaire and thinking-aloud; n = 15-27 patients). We explored the GPQ structure and performed path analyses to test conditional mediation relationships. Exploratory factor analysis showed two factors: 'Fatigue-avoidance goal' and 'Mood-management goal' (39.3% and 13.9% of explained variance, respectively). The activity avoidance pattern fully mediated the relation between both catastrophizing and fatigue-avoidance goals with fatigue. The study shows initial findings about the usefulness of the GPQ-F as a tool to analyze goal preferences related to fatigue in fibromyalgia. The results supported the mediational role of activity avoidance patterns in the relationship between preference for fatigue-avoidance goals and fatigue.
Learn More >Neuropathic pain (NP) is a devastating chronic pain condition affecting roughly 80% of the spinal cord injury (SCI) patient population. Current treatment options are largely ineffective and neurophysiological mechanisms of NP are not well-understood. Recent studies in neuroimaging have suggested that NP patients have differential patterns of functional activity that are dependent upon the neurological condition causing NP. We conducted an exploratory pilot study to examine functional activation and connectivity in SCI patients with chronic NP compared to SCI patients without NP. We developed a novel somatosensory attention task to identify short term fluctuations in neural activity related to NP vs. non-painful somatosensation using functional magnetic resonance imaging (fMRI). We also collected high-resolution resting state fMRI to identify connectivity-based correlations over time between the two groups. We observed increased activation during focus on NP in brain regions associated with somatosensory integration and representational knowledge in pain subjects when compared with controls. Similarly, NP subjects showed increased connectivity at rest in many of the same areas of the brain, with positive correlations between somatomotor networks, the dorsal attention network, and regions associated with pain and specific areas of painful and non-painful sensation within our cohort. Although this pilot analysis did not identify statistically significant differences between groups after correction for multiple comparisons, the observed correlations between NP and functional activation and connectivity align with hypotheses regarding pain, and provide a well-controlled preliminary basis for future research in this severely understudied patient population. Altogether, this study presents a novel task, identifies regions of increased task-based activation associated with NP after SCI in the insula, prefrontal, and medial inferior parietal cortices, and identifies similar regions of increased functional connectivity associated with NP after SCI in sensorimotor, cingulate, prefrontal, and inferior medial parietal cortices. This, along with our complementary results from a structurally based analysis, provide multi-modal evidence for regions of the brain specific to the SCI cohort as novel areas for further study and potential therapeutic targeting to improve outcomes for NP patients.
Learn More >A national clinical registry was established in the Netherlands containing data directly sampled from electronic health record systems of physical therapists (PTs). This registry aims to evaluate the potential of patient reported outcome measures (PROMs) to develop quality indicators (QIs) in physical therapy care.
Learn More >Pain and joint deformity are the most common symptoms of hip osteoarthritis (OA). However, no significant association between pain and severity of radiographic lesions has been reported. Recently, central sensitization has been suggested as an underlying mechanism of pain in OA. We investigated the involvement of radiologic severity or central sensitization in the clinical manifestation of hip OA with various degrees of joint deformity.
Learn More >Nonsteroidal anti-inflammatory drugs are widely used for migraine, but gastrointestinal tolerability limits use. We previously reported results from the first treatment period of this 2-period, randomized, controlled study comparing DFN-15-an oral, ready-made liquid solution of a selective cyclo-oxygenase-2 inhibitor celecoxib-with placebo for the acute treatment of a moderate-severe migraine attack. Herein, we report the effects of treatment for the second treatment period.
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