Pain
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Informing patients about potential side effects of pain treatment is a requirement that protects patients and aids decision making, but it increases the likelihood of unwanted nocebo side effects. If patients do not desire all side-effect information, it may be possible to ethically reduce nocebo effects through authorized concealment of side effects, whereby patients and clinicians engage in shared decision-making to regulate the disclosure of side-effect information. Currently, there is no experimental data clarifying the factors that causally influence desire for side-effect information in pain treatment. ⋯ Results were not moderated by participants' level of contact with the health care system, chronic health condition, or clinical pain history. Additional analyses indicated that low side-effect severity and frequency lessen desire for side-effect information because these variables reduce belief that side-effect information will be needed in the future and lower feelings of anticipated regret. The experiments identify situational and individual-difference factors that decrease the desire for side-effect information and provide evidence on when and for whom it may be useful for physicians to engage in shared medical decision-making with the goal of reducing nocebo side effects.
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Total knee arthroplasty (TKA) is the end-stage treatment of knee osteoarthritis (OA), and approximately 20% of patients experience chronic postoperative pain. Studies indicate that inflammatory biomarkers might be associated with pain in OA and potentially linked to the development of chronic postoperative pain after TKA. This study aimed to (1) evaluate preoperative serum levels of inflammatory biomarkers in patients with OA and healthy control subjects, (2) investigate preoperative differences of inflammatory biomarker profiles in subgroups of patients, and (3) compare subgroups of patients with and without postoperative pain 12 months after surgery. ⋯ The 12-months postoperative VAS and KOOS scores were significantly different between subgroups of patients ( P < 0.05). This study identified differences in specific inflammatory biomarker profiles when comparing patients with OA and control subjects. Cluster analysis identified 2 subgroups of patients with OA, with one subgroup demonstrating comparatively worse 12-month postoperative pain intensity and function scores.
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Dental pulp tissue is densely innervated by afferent fibers of the trigeminal ganglion. When bacteria cause dental decay near the pulpal tissue, a strong neuronal and immune response occurs, creating pulpitis, which is associated with severe pain and pulp tissue damage. Neuroimmune interactions have the potential to modulate both the pain and pathological outcome of pulpitis. ⋯ We found that the neuropeptide CGRP, facilitated the recruitment of myeloid cells into the pulp while also increasing spontaneous pain-like behavior 20% to 25% at an early time point. Moreover, when we depleted neutrophils and monocytes, we found that there was 20% to 30% more sensory afferent loss and increased presence of bacteria in deeper parts of the tissue, whereas there was a significant reduction in mechanical pain response scores compared with the control group at a later time point. Overall, we showed that there is a crosstalk between peptidergic neurons and neutrophils in the pulp, modulating the pain and inflammatory outcomes of the disease.
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Lipid-rich diet is the major cause of obesity, affecting 13% of the worldwide adult population. Obesity is a major risk factor for metabolic syndrome that includes hyperlipidemia and diabetes mellitus. The early phases of metabolic syndrome are often associated with hyperexcitability of peripheral small diameter sensory fibers and painful diabetic neuropathy. ⋯ We then deciphered the mechanisms involved in the heat hypersensitivity of mice and found that serum from high-fat diet-fed mice was enriched in lysophosphatidylcholine (LPC16:0, LPC18:0, and LPC18:1). These enriched lipid species directly increased the activity of DRG neurons through activating the lipid sensitive ASIC3 channel. Our results identify ASIC3 channel in DRG neurons and circulating lipid species as a mechanism contributing to the hyperexcitability of nociceptive neurons that can cause pain associated with lipid-rich diet consumption and obesity.
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Pain is the most common symptom experienced by patients with sickle cell disease (SCD) throughout their lives and is the main cause of hospitalization. Despite the progress that has been made towards understanding the disease pathophysiology, major gaps remain in the knowledge of SCD pain, the transition to chronic pain, and effective pain management. Recent evidence has demonstrated a vital role of gut microbiota in pathophysiological features of SCD. ⋯ Fecal material transplantation from mice with SCD to wild-type mice resulted in tactile allodynia (0.95 ± 0.17 g vs 0.08 ± 0.02 g, von Frey test, P < 0.001), heat hyperalgesia (15.10 ± 0.79 seconds vs 8.68 ± 1.17 seconds, radiant heat, P < 0.01), cold allodynia (2.75 ± 0.26 seconds vs 1.68 ± 0.08 seconds, dry ice test, P < 0.01), and anxiety-like behaviors (Elevated Plus Maze Test, Open Field Test). On the contrary, reshaping gut microbiota of mice with SCD with FMT from WT mice resulted in reduced tactile allodynia (0.05 ± 0.01 g vs 0.25 ± 0.03 g, P < 0.001), heat hyperalgesia (5.89 ± 0.67 seconds vs 12.25 ± 0.76 seconds, P < 0.001), and anxiety-like behaviors. These findings provide insights into the relationship between gut microbiota dysbiosis and pain in SCD, highlighting the importance of gut microbial communities that may serve as potential targets for novel pain interventions.