Pain
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Previous studies estimate that >40% of long-stay nursing home (NH) residents experience persistent pain, with 20% of residents in pain receiving no analgesics. Strengthened NH surveyor guidance and improved pain measures on the Minimum Data Set 3.0 were introduced in March 2009 and October 2010, respectively. This study aimed to provide estimates after the important initiatives of (1) prevalence and correlates of persistent pain; and (2) prevalence and correlates of untreated or undertreated persistent pain. ⋯ One in 5 NH residents has persistent pain. Although this estimate is greatly improved, many residents may be undertreated. The disturbing disparities in untreated and undertreated pain need to be addressed.
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Patients with idiopathic trigeminal neuralgia (TN) were categorised into 3 subtypes (n = 225). Group 1 (n = 155, 68.9%) had TN without concomitant pain, group 2 (n = 32, 14.2%) had TN with intermittent concomitant pain, and group 3 (n = 39, 16.9%) had TN with autonomic symptoms. We tested 2 hypotheses: (1) that different pain profiles would be associated with the different groups; (2) that the severe pain associated with TN would impact negatively on activities of daily living and thereby result in disability as defined by the World Health Organisation. ⋯ Prior to referral, only 54% had been prescribed carbamazepine while opioids had been prescribed in 14.6% of the patients. Prior to referral, over 80% had already been to 1 specialist centre which had not provided appropriate management. Patients with TN report varied characteristics but all result in some degree of psychosocial disability especially before adequate therapy is attained.
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Opioids are the gold standard for pharmacological treatment of neuropathic pain, but their analgesic effects are unsatisfactory in part due to nerve injury-induced downregulation of opioid receptors in dorsal root ganglia (DRG) neurons. How nerve injury drives such downregulation remains elusive. DNA methyltransferase (DNMT)-triggered DNA methylation represses gene expression. ⋯ Mechanistically, DNMT3a regulation of Oprm1 gene expression required the methyl-CpG-binding protein 1, MBD1, as MBD1 knockout resulted in the decreased binding of DNMT3a to the Oprm1 gene promoter and blocked the DNMT3a-triggered repression of Oprm1 gene expression in DRG neurons. These data suggest that DNMT3a is required for nerve injury-induced and MBD1-mediated epigenetic silencing of the MOR and KOR in the injured DRG. DNMT3a inhibition may serve as a promising adjuvant therapy for opioid use in neuropathic pain management.
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Chemotherapy-induced peripheral neuropathy is one of the most common dose-limiting side effects of cancer treatment. Currently, there is no Food and Drug Administration-approved treatment available. Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase whose function includes regulation of α-tubulin-dependent intracellular mitochondrial transport. ⋯ HDAC6 inhibition restored the loss of intraepidermal nerve fiber density in cisplatin-treated mice. Our results demonstrate that pharmacological inhibition of HDAC6 completely reverses all the hallmarks of established cisplatin-induced peripheral neuropathy by normalization of mitochondrial function in dorsal root ganglia and nerve, and restoration of intraepidermal innervation. These results are especially promising because one of the HDAC6 inhibitors tested here is currently in clinical trials as an add-on cancer therapy, highlighting the potential for a fast clinical translation of our findings.
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Breathing techniques are commonly used to alleviate pain. Despite their frequent use, surprisingly little is known about their efficacy as well as their underlying physiological mechanisms. The purpose of this systematic review is to summarize and critically appraise the results of existing studies on the association between respiration and pain, and to highlight a potential physiological mechanism underlying the respiration-pain connection. ⋯ Furthermore, paced slow breathing is associated with pain reduction in some of the studies, but evidence elucidating the underlying physiological mechanisms of this effect is lacking. Here, we focus on the potential role of the cardiovascular system on the respiratory modulation of pain. Further research is definitely warranted.