Mol Pain
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Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder, characterized by loss of algesthesis and inability to sweat. CIPA is known to be caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene ( NTRK1). However, the details of NTRK1 mutations in Chinese CIPA patients remain unclear. ⋯ Interestingly, we discovered two forms of novel recurrent mutations: the first was a large intragenic deletion c.429-374_717 + 485del mediated by recombination between Alu elements, and the second was a deep intronic substitutions c.[851-798C > T;851-794C > G]. All probands were homozygotes or compound heterozygotes of these mutations. Current findings expand our knowledge about the mutation spectrum of NTRK1 in Chinese CIPA patients and provide more evidence for precise diagnosis of the clinically suspected patients with CIPA.
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Painful neuropathy is a frequent comorbidity in diabetes. Zucker diabetic fatty (fa/fa) rats develop type 2 diabetes spontaneously with aging and show nociceptive hypersensitivity at the age of 13 weeks. In preclinical and clinical studies, the treatment of diabetic neuropathy is challenging, but complementary medicine such as transcutaneous auricular vagus nerve stimulation (taVNS) appears beneficial to the relief of neuropathic pain. ⋯ We conclude that daily 30-min taVNS sessions lessen diabetic neuropathy development by enhancing serotonergic function in genetically diabetes prone individuals. Perspective This article presents taVNS as a new approach to inhibit the development of diabetic neuropathy in genetically prone individuals. This approach could potentially help clinicians who seek to avoid the complication of neuropathic pain in diabetic patient or to relieve the pain if there was one.
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Sodium channels play pivotal roles in health and diseases due to their ability to control cellular excitability. The pore-forming α-subunits (sodium channel alpha subunits) of the voltage-sensitive channels (i.e., Nav1.1-1.9) and the nonvoltage-dependent channel (i.e., Nax) share a common structural motif and selectivity for sodium ions. We hypothesized that the actin-based nonmuscle myosin II motor proteins, nonmuscle myosin heavy chain-IIA/myh9, and nonmuscle myosin heavy chain-IIB/myh10 might interact with sodium channel alpha subunits to play an important role in their transport, trafficking, and/or function. ⋯ Myh10 coexpression also hyperpolarized voltage-dependent activation and steady-state fast inactivation of Nav1.8 channels. In addition, coexpression of myh10 reduced ( P < 0.01) the offset of fast inactivation and the amplitude of the ramp currents of Nav1.8 channels. These results indicate that nonmuscle myosin heavy chain-IIs interact with sodium channel alpha subunits subunits in an isoform-dependent manner and influence their functional properties.
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Meta Analysis
[EXPRESS] Quantitative Evaluation to Efficacy and Safety of Therapies for Psoriasis: A Network Meta-Analysis.
Therapies treating psoriasis can be categorized into five classes according to their mechanism: anti-metabolites (AM), anti-interleukin-12/23 agents (anti-IL12/23), anti-interleukin-17 agents (anti-IL17), anti-T-cell agent (ANT), and anti-tumor necrosis factor-α agent (anti-TNF-α). This network meta-analysis (NMA) aimed to give a quantitative and systemic evaluation of safety and efficacy for the five kinds of therapies mentioned above. Odds ratios and mean differences were calculated to evaluate binary and continuous outcomes, respectively. ⋯ Additionally, node splitting showed that no inconsistency appeared between the direct and indirect comparisons. Anti-IL12/23 was the most recommended therapy according to this NMA. Anti-IL17 had similar efficacy to anti-IL12/23 but should be applied with caution since it has poor performance in safety outcomes.
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Primary sensory neurons in the dorsal root ganglia and trigeminal ganglia are responsible for sensing mechanical and thermal stimuli, as well as detecting tissue damage. These neurons express ion channels that respond to thermal, mechanical, or chemical cues, conduct action potentials, and mediate transmitter release. These neurons also express a large number of G-protein coupled receptors, which are major transducers for extracellular signaling molecules, and their activation usually modulates the primary transduction pathways. ⋯ On the other hand, receptors that couple to Gi/o proteins, such as opioid or GABAB receptors, are generally inhibitory. Their activation counteracts the effect of Gs-stimulation by inhibiting adenylate cyclase, as well as exerts effects on ion channels, usually resulting in decreased excitability. This review will summarize knowledge on Gi-coupled receptors in sensory neurons, focusing on their roles in ion channel regulation and discuss their potential as targets for analgesic and antipruritic medications.