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The reciprocal interaction between pain and negative affect is acknowledged but pain-related alterations in brain circuits involved in this interaction, such as the mediodorsal thalamus (MDThal), still require a better understanding. We sought to investigate the relationship between MDThal circuitry, negative affect and pain severity in chronic musculoskeletal pain. For these analyses, participants with chronic knee pain (CKP, n=74) and without (n=36) completed magnetic resonance imaging scans and questionnaires. Seed-based MDThal functional connectivity (FC) was compared between groups. Within CKP group, we assessed the interdependence of MDThal FC with negative affect. Finally, post-hoc moderation analysis explored whether burden of pain influences affect-related MDThal FC. The CKP group showed altered MDThal FC to hippocampus, ventromedial prefrontal cortex, and subgenual anterior cingulate. Furthermore, in CKP group, MDThal connectivity correlated significantly with negative affect in several brain regions, most notably the medial prefrontal cortex, and this association was stronger with increasing pain burden and absent in pain-free controls. In conclusion, we demonstrate mediodorsal thalamo-cortical dysconnectivity in chronic pain with areas linked to mood disorders and associations of MDThal FC with negative affect. Moreover, burden of pain seems to enhance affect sensitivity of MDThal FC. These findings suggest mediodorsal thalamic network changes as possible drivers of the detrimental interplay between chronic pain and negative affect.
Learn More >Levodopa is the most effective symptomatic therapy for Parkinson's disease, but patients with advanced Parkinson's disease develop motor fluctuations with chronic oral levodopa therapy. Foslevodopa-foscarbidopa is a soluble formulation of levodopa and carbidopa prodrugs that is delivered as a 24-h/day continuous subcutaneous infusion, and we aimed to assess the safety and efficacy of this formulation in patients with advanced Parkinson's disease.
Learn More >The treatment of chronic neuropathic pain remains one of the most challenging of all neurological diseases and very much an art. There exists no consensus for the optimal management of this condition at the moment. Gaining inspiration from recent studies which pointed out the involvement of brain-associated carbonic anhydrase (CA, EC 4.2.1.1) isoform VII in the pathology of various neurodegenerative diseases, which highlighted the relationship between selective inhibition of this isozyme and relieve of neuropathic pain, herein we report the synthesis and CA VII inhibitory activity of novel 4-(3-alkyl/benzyl-guanidino)benzenesulfonamides. Ten benzyl-substituted and five alkyl-substituted 4-guanidinobenzenesulfonamide derivatives were obtained, some of which (, , and ) exhibited satisfactory selectivity towards CA VII over CA I and II, with K-s in the subnanomolar range and good selectivity indexes for inhibiting the target versus the off-target isoforms.
Learn More >Wrist arthroplasties have not achieved clinical outcomes comparable to those of shoulders and knees, being offered low-demand patients due to a high failure rate. In the 90s, there were no wrist arthroplasties available for high-demand patients. An experimental setup for the development of a new wrist arthroplasty intended for all wrist patients were done. A long-term final follow-up to evaluate the performance of the experimental arthroplasty was performed. A novel uncemented modular wrist prosthesis with conical threaded fixation, metal-on-metal coupling and ball-and-socket articulation was developed. In an experimental study, eight patients (7 men, 53 years of age) were operated between 2001 and 2003, to treat non-inflammatory primary or secondary osteoarthritis. Published mid-term results (7-9 years) demonstrated satisfactory function, but two arthroplasties were converted to arthrodesis due to infection. At final follow-up 15-20 years after primary surgery, the remaining six patients still had a wrist arthroplasty (in three the original) in situ. The clinical results were good. Low pain (median = 0), Quick Disability of Arm, Shoulder and Hand (QDASH median 11) and Patient Rated Wrist and Hand Evaluation (PRWHE median = 14) scores were reported. Wrist active range of motion (AROM) was 64% and grip strength 86% compared to the opposite side. None regretted choosing arthroplasty knowing the outcome. Despite technical errors and the implementation of an incomplete prototype, this new concept for arthroplasty has demonstrated promising long-term fixation, a stable articulation with good range of motion, satisfactory function and pain reduction in high-demand patients. Level IV (Therapeutic).
Learn More >[Purpose] In this pilot study, we investigated the effectiveness of physical therapist-delivered acceptance and commitment therapy in older outpatients with knee osteoarthritis and chronic pain. [Participants and Methods] This single-center, open-label, parallel-group pilot randomized controlled trial included 30 patients assigned to the physical therapist-delivered acceptance and commitment therapy group (n=15) and the usual care physical therapy-only group (n=15). Both treatments were administered once a week for 8 weeks. Evaluation was performed 4 weeks before intervention, pre-intervention, post-intervention, and 4 weeks after intervention. The primary outcome was diagnosis of a physical disability, and secondary outcomes included psychological inflexibility, pain intensity, anxiety, depression, physical function, and objectively measured physical activity. [Results] Physical therapist-delivered acceptance and commitment therapy had a limited effect on physical disability, although we observed a favorable tendency. With regard to secondary outcomes, physical therapist-delivered acceptance and commitment therapy did not show significant effects. Notably, 15 patients withdrew from this study and 6 were diagnosed with coronavirus disease. [Conclusion] Physical therapist-delivered acceptance and commitment therapy did not appear to show significant effects in the present study. It is necessary to correct these issues in this study, and future studies are warranted to investigate the effects of this therapy.
Learn More >This study aimed to investigate the effects of progressive postural control exercise (PPCE) vs core stability exercise (CSE) in patients with chronic low back pain (CLBP).
Learn More >An important part of providing pain science education is to first assess baseline knowledge and beliefs about pain, thereby identifying misconceptions and establishing individually-tailored learning objectives. The Concept of Pain Inventory (COPI) was developed to support this need. This study aimed to characterize concept of pain in care-seeking youth and their parents, to examine its clinical and demographic correlates, and to identify conceptual gaps.
Learn More >Chronic pain is a distinct complication that profoundly affects the lives of individuals with sickle cell disease (SCD). Chronic SCD pain emerges with increasing age and is very prevalent in adults. The pathophysiology of chronic SCD pain is likely distinct from acute SCD pain and therefore needs a different treatment approach. Clinical trials evaluating the treatment of chronic SCD pain are lacking and treatment currently relies on evidence from other chronic pain conditions. Continued investigations into the underlying causes of chronic SCD pain are needed, and clinical trials focused on chronic pain therapy are imperative.
Learn More >Transdermal fentanyl patches are an effective alternative to the sustained release of oral morphine for chronic pain management. Due to the narrow therapeutic range of fentanyl, the concentration of fentanyl in the blood needs to be carefully monitored. Only then can effective pain relief be achieved while avoiding adverse effects such as respiratory depression. This study developed a physics-based digital twin of a patient by implementing drug uptake, pharmacokinetics, and pharmacodynamics models. The twin was employed to predict the effect of conventional fentanyl transdermal in a 20-80-year-old virtual patient. The results show that, with increasing age, the maximum transdermal fentanyl flux and maximum concentration of fentanyl in the blood decreased by 11.4% and 7.0%, respectively. However, the results also show that as the patient's age increases, the pain relief increases by 45.2%. Furthermore, the digital twin was used to propose a tailored therapy based on the patient's age. This predesigned therapy customized the duration of applying the commercialized fentanyl patches. According to this therapy, a 20-year-old patient needs to change the patch 2.1 times more frequently than conventional therapy, which leads to 30% more pain relief and 315% more time without pain. In addition, the digital twin was updated by the patient's pain intensity feedback. Such therapy increased the patient's breathing rate while providing effective pain relief, so a safer treatment. We quantified the added value of a patient's physics-based digital twin and sketched the future roadmap for implementing such twin-assisted treatment into the clinics.
Learn More >With increased hospitalizations and deaths related to opioid use disorder, there is an impetus for federal and private insurance companies to provide coverage for integrative treatments that address pain. The Centers for Disease Control and Prevention (CDC) and the current literature recommend that nonpharmacological and nonopioid treatments must be considered for chronic pain management. The continued examination of potential coverage and cost-effectiveness for opioid-sparing alternatives with proven efficacy is critical for physicians who treat chronic pain.
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