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Cognitive impairment associated with chronic pain remains relatively poorly understood. Use of analgesic drugs and often present co-morbidities in patients can preclude conclusions of causative relationships between chronic pain and cognitive deficits. Here, the impact of pain resulting from spinal nerve ligation (SNL) injury in rats on short and long-term memory was assessed in the novel object recognition (NOR) task. To understand if chronic pain seizes the limited cognitive resources that are available at any given time, task difficulty was varied by using either very different (i.e., easy task) or similar (i.e., difficult task) pairs of objects. Nerve-injured, male rats exhibited no short or long-term memory deficits under easy task conditions. However, unlike sham-operated controls, injured rats showed deficits in both short and long-term memory by failing to differentiate similar objects in the difficult task version. In SNL rats, duloxetine produced anti-allodynic effects and ameliorated long-term memory deficits in the difficult task suggesting benefits of pain relief possibly complemented by noradrenergic mediated cognitive enhancement. Together these data suggest chronic pain reversibly takes up a significant amount of limited cognitive resources, leaving sufficient available for easy, but not difficult, tasks. PERSPECTIVE: Memory deficits in a rat model of chronic pain were only seen when the cognitive load was high, i.e., in a difficult task. Acute treatment with duloxetine was sufficient to relieve memory deficits, suggesting chronic pain induces memory deficits by seizing limited cognitive resources to the detriment of task-related stimuli.
Learn More >Changes in inflammatory cytokine levels contribute to the induction and maintenance of neuropathic pain. We have shown that external low intensity focused ultrasound (liFUS) reduces allodynia in a common peroneal nerve injury (CPNI). Here, we investigate an underlying mechanism of action for this treatment and measure the effect of liFUS on inflammatory markers.
Learn More >Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, and tyrosine kinase 2. We aimed to assess the efficacy and safety of upadacitinib compared with placebo for the treatment of moderate-to-severe atopic dermatitis.
Learn More >This report investigates the impact of a remote physical activity intervention on self-efficacy, satisfaction with functioning, and health-related quality of life (HRQOL) as assessed by the SF-36 in obese older adults with chronic pain. The intervention was group-mediated in nature and based in social cognitive theory and mindfulness-based relapse prevention.
Learn More >To describe the methodology and implications of the patient-identified most bothersome symptom (PI-MBS) measure used in the phase 3, multicenter, randomized, double-blind, placebo-controlled, and parallel-group PROMISE-2 trial and to evaluate the contribution of this measure to the assessment of the preventive migraine benefits of treatment.
Learn More >To evaluate the analgesic efficacy of a portable, disposable and home self-applied transcutaneous electrical nerve stimulation device during migraine attacks.
Learn More >The need for safer pain-management therapies with decreased abuse liability inspired a novel drug design that retains μ-opioid receptor (MOR)-mediated analgesia, while minimizing addictive liability. We recently demonstrated that targeting the dopamine D receptor (DR) with highly selective antagonists/partial agonists can reduce opioid self-administration and reinstatement to drug seeking in rodent models without diminishing antinociceptive effects. The identification of the DR as a target for the treatment of opioid use disorders prompted the idea of generating a class of ligands presenting bitopic or bivalent structures, allowing the dual-target binding of the MOR and DR. Structure-activity relationship studies using computationally aided drug design and binding assays led to the identification of potent dual-target leads (, , and ), based on different structural templates and scaffolds, with moderate (sub-micromolar) to high (low nanomolar/sub-nanomolar) binding affinities. Bioluminescence resonance energy transfer-based functional studies revealed MOR agonist-DR antagonist/partial agonist efficacies that suggest potential for maintaining analgesia with reduced opioid-abuse liability.
Learn More >Acute pain is the main complication of sickle cell disease. Chronic and neuropathic pain may also be experienced but have not been formally described in Jamaican patients. A cross-sectional study was conducted to determine their prevalence and characteristics, and to determine the common pain locations and modalities of management.
Learn More >(1) Background: In many surgical procedures, regional analgesia (RA) techniques are associated with improved postoperative analgesia compared to systemic pain treatment. As continuous RA requires time and experienced staff, it would be helpful to identify settings in which continuous RA has the largest benefit. (2) Methods: On the basis of 23,911 data sets from 179 German and Austrian hospitals, we analyzed the association of perioperative RA with patient-reported pain intensity, functional impairment of movement, nausea and opioid use for different surgeries. Regression analyses adjusted for age, sex and preoperative pain were performed for each surgery and the following groups: patients receiving continuous RA (surgery and ward; RA++), RA for surgery only (RA+-) and patients receiving no RA (RA–). (3) Results: Lower pain scores in the RA++ compared to the RA– group were observed in 13 out of 22 surgeries. There was no surgery where pain scores for RA++ were higher than for RA–. If maximal pain, function and side effects were combined, the largest benefit of continuous RA (RA++) was observed in laparoscopic colon and sigmoid surgery, ankle joint arthrodesis, revision (but not primary) surgery of hip replacement, open nephrectomy and shoulder surgery. The benefit of RA+- was lower than that of RA++. (4) Discussion: The additional benefit of RA for the mentioned surgeries is larger than in many other surgeries in clinical routine. The decision to use RA in a given surgery should be based on the expected pain intensity without RA and its additional benefits.
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