Pain
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Long-term opioid therapy (LTOT) is associated with increased risk for depression. It is not known if the frequency of opioid use during LTOT is associated with new-onset depression. We used Optum's de-identified Integrated Claims-Clinical dataset (2010-2018) to create a cohort of 5146 patients, 18 to 80 years of age, with an encounter or claims in the year before new LTOT. ⋯ In LTOT, risk for new depression episodes is up to 40% greater in near-daily users compared with occasional users. Patients could reduce depression risk by avoiding opioid use on as many low pain days as possible. Repeated screening for depression during LTOT is warranted.
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Endometriosis is a chronic and debilitating condition, commonly characterised by chronic pelvic pain (CPP) and infertility. Chronic pelvic pain can be experienced across multiple pelvic organs, with comorbidities commonly effecting the bowel, bladder, and vagina. Despite research efforts into endometriosis pathophysiology, little is known about how endometriosis induces CPP, and as such, therapeutic interventions are lacking. ⋯ Additionally, we found that mice with fully developed endometriosis displayed hypersensitivity evoked by (1) vaginal distension, (2) colorectal distension, (3) bladder distension, and (4) cutaneous thermal stimulation, compared to their sham counterparts. Moreover, endometriosis mice displayed alterations in spontaneous behaviour indicative of (5) altered bladder function and (6) anxiety. This model creates a foundation for mechanistical studies into the diffuse CPP associated with endometriosis and the development of targeted therapeutic interventions to improve the quality of life of women with endometriosis.
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Although nonsteroidal anti inflammatory drugs are superior to opioids in dental pain management, opioids are still prescribed for dental pain in the United States. Little is known about the serious adverse outcomes of short-acting opioids within the context of dental prescribing. The objective of this study was to evaluate adverse outcomes and persistent opioid use (POU) after opioid prescriptions by dentists, based on whether opioids were overprescribed or within recommendations. ⋯ Visits associated with mild pain and those with substance use disorders had the highest risk of both outcomes. Findings from this study demonstrate that dental prescribing of opioids was associated with adverse outcomes and POU, even when prescriptions were concordant with guidelines. Additional efforts are required to improve analgesic prescribing in dentistry, especially in groups at high risk of opioid-related adverse outcomes.
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Several bone conditions, eg, bone cancer, osteoporosis, and rheumatoid arthritis (RA), are associated with a risk of developing persistent pain. Increased osteoclast activity is often the hallmark of these bony pathologies and not only leads to bone remodeling but is also a source of pronociceptive factors that sensitize the bone-innervating nociceptors. Although historically bone loss in RA has been believed to be a consequence of inflammation, both bone erosion and pain can occur years before the symptom onset. ⋯ By contrast, we found that inhibiting osteoclast activity and acid-sensing ion channel 3 signaling prevented the development of B02/B09-mediated mechanical hypersensitivity. Moreover, we have identified secretory phospholipase A2 and lysophosphatidylcholine 16:0 as critical components of B02/B09-induced pain-like behavior and shown that treatment with a secretory phospholipase A2 inhibitor reversed B02/B09-induced mechanical hypersensitivity and bone erosion. Taken together, our study suggests a potential link between bone erosion and pain in a state of subclinical inflammation and offers a step forward in understanding the mechanisms of bone pain in diseases such as RA.
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Capsaicin is a specific agonist of transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptors. Capsaicin not only produces acute pain but also leads to long-lasting analgesia in patients with chronic pain. Although capsaicin-induced TRPV1 and Ca 2+ /calpain-dependent ablation of axonal terminals is necessary for long-lasting analgesia, the mechanisms underlying capsaicin-induced ablation of axonal terminals and its association with analgesia are not fully understood. ⋯ Despite the suggested involvement of TRPV1 Ser801 phosphorylation on microtubule integrity, capsaicin-induced analgesia was not affected in TRPV1 S801A knock-in mice. In conclusion, capsaicin-induced depolymerization of axonal microtubules determined capsaicin-induced ablation of nociceptive terminals and the extent of analgesia. Further understanding of TRPV1/Ca 2+ -dependent mechanisms of capsaicin-induced ablation and analgesia may help to improve the management of chronic pain.