Articles: human.
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Central sensitization (CS) is believed to play a role in many chronic pain conditions. Direct non-invasive recording from single nociceptive neurons is not feasible in humans, complicating CS establishment. This review discusses how secondary hyperalgesia (SHA), considered a manifestation of CS, affects physiological measures in healthy individuals and if these measures could indicate CS. It addresses controversies about heat sensitivity changes, the role of tactile afferents in mechanical hypersensitivity and detecting SHA through electrical stimuli. Additionally, it reviews the potential of neurophysiological measures to indicate CS presence. ⋯ Gathering evidence for CS in humans is a crucial research focus, especially with the increasing interest in concepts such as 'central sensitization-like pain' or 'nociplastic pain'. This review clarifies which readouts, among the different behavioural and neurophysiological proxies tested in experimental settings, can be used to infer the presence of CS in humans.
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Anatomic features of neuromas have been explored in imaging studies. However, there has been limited research into these features using resected, ex vivo human neuroma specimens. The aim of this study was to investigate the influence that time may have on neuroma growth and size, and the clinical significance of these parameters. ⋯ This study suggests that neuromas seem to continue to grow over time and that smaller nerves may form relatively larger neuromas. In addition, sensory nerves develop relatively larger neuromas compared with mixed nerves. Neuroma size does not appear to correlate with pain severity. These findings may stimulate future research efforts and contribute to a better understanding of symptomatic neuroma development.
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Voltage-gated sodium (Na v ) channels present untapped therapeutic value for better and safer pain medications. The Na v 1.8 channel isoform is of particular interest because of its location on peripheral pain fibers and demonstrated role in rodent preclinical pain and neurophysiological assays. To-date, no inhibitors of this channel have been approved as drugs for treating painful conditions in human, possibly because of challenges in developing a sufficiently selective drug-like molecule with necessary potency not only in human but also across preclinical species critical to the preclinical development path of drug discovery. ⋯ In this report, we have leveraged numerous physiological end points in nonhuman primates to evaluate the analgesic and pharmacodynamic activity of a novel, potent, and selective Na v 1.8 inhibitor compound, MSD199. These pharmacodynamic biomarkers provide important confirmation of the in vivo impact of Na v 1.8 inhibition on peripheral pain fibers in primates and have high translational potential to the clinical setting. These findings may thus greatly improve success of translational drug discovery efforts toward better and safer pain medications, as well as the understanding of primate biology of Na v 1.8 inhibition broadly.
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Randomized Controlled Trial
Effects of Sub-Anesthetic Oro-Mucosal Dexmedetomidine on Sleep in Humans: A Randomized, Controlled Pharmacokinetics-Pharmacodynamics Study.
The locus coeruleus noradrenergic system may provide a potential new target for pharmacologic insomnia treatment, particularly in patients suffering from elevated distress. The selective α 2 -noradrenergic agonist dexmedetomidine attenuates locus coeruleus activity in subanesthetic doses, yet no adequate nonparental delivery systems of dexmedetomidine are currently available. To examine the feasibility of oromucosal dexmedetomidine administration, the authors developed two distinct-one sublingual and one buccal-oromucosal, fast-disintegrating dexmedetomidine formulas tailored for self-administration. Here, the authors established the formulas' pharmacokinetic and pharmacodynamic profiles. ⋯ The favorable pharmacokinetic and pharmacodynamic profile of oromucosal dexmedetomidine delivery warrants further dose-finding and clinical studies to establish the exact roles of α 2 receptor agonism in pharmacologic sleep enhancement and as a possible novel mechanism to alleviate stress-related insomnia.
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Review Historical Article
Morphological and Clinical Aspects of Pott's Disease in Ancient Human Remains: A Scoping Review.
The present study is a scoping review of the literature on Pott disease in ancient human remains. ⋯ Although most of the findings are consistent with the literature, since the majority of the human remains were from Europe and the Near Middle East, more research is necessary in other sectors of the world. The suggestion of a male predominance needs to be confirmed and questions about the possible pathognomic role of rib lesions as well Serpes endocranica symmetrica (SES) represent further areas of research that need to be explored.