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Physiology of pain
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2015
Philip J. Siddal, Michael J. Cousins, Peter Kam
The main channels responsible for inward membrane currents in nociception are voltage-activated sodium and calcium channels, whereas the outward current is mediated by potassium ions. TRP ion channels are a family of non-selective cation channels with a variable permeability to Ca+ + ions. Vanilloid receptor–related TRP channels (TRPV) are activated by a variety of sensory stimuli: capsaicin, heat (> 43°C), acid, inflammation, ischaemia and endogenous lipids. The ASIC is activated by extracellular acid (during inflammation and ischaemia of tissues). The purinergic receptor (P2X3) is an ATP-gated nociceptor responsible for hyperalgesia in neuropathic pain. Serotonin is an endogenous pain-producing mediator released by platelets and enterochromaffin cells.
P2X3-P2X7 SNPs and gene-gene and gene-environment interactions on pediatric asthma
Published in Journal of Asthma, 2023
Lingxue Li, Bing Wei, Jingjing Jia, Mo Li, Mengyang Ren, Shinan Zhang
As pointed out by Abdulqawi, Dockry, and Holt et al. (22), P2X3 receptor antagonist were effective for refractory chronic cough . Clinical trials such as phase II a, II b and III had shown that P2X3 antagonist significantly reduced cough frequency and severity, improved quality of life, especially ATP-evoked cough was significantly inhibited (23–26). ATP is a ligand for P2X3 and P2X7. Prolonged inhalation of ATP caused bronchoconstriction, with a greater response in the asthmatic individuals (27,28). Thus, when the influence of disease severity was excluded, the above conclusions were verified by a stratified analysis of cough or not in asthmatic children, our results suggested that the rs10896611, rs2276038 and rs3781899 of P2X3 minor alleles were associated with childhood asthma with cough, where they were strongly harmful. For the other two SNPs, no increased risks of childhood asthma with cough were found.
Research progress of coumarins and their derivatives in the treatment of diabetes
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Yinbo Pan, Teng Liu, Xiaojing Wang, Jie Sun
Diabetic neuralgia (DNP) is one of the most common complications of diabetes76. DNP is related to the enhancement of peripheral sensory nerve excitability, involving various ion channels, receptor expression and up-regulation of function. P2X3 receptor is a member of P2X family of purine receptors and participates in many neuropathological pain processes including DNP. P2X3 receptor is a non-selective ligand-gated cation channel, which is mainly distributed in some sympathetic neurons, sensory neurons and nucleus tractus solitarius, mainly in small and medium ganglion cells. P2X3 receptor increases pain when its expression is up-regulated or its activity is enhanced and decreases pain when its expression is down or desensitised, indicating that P2X3 receptor is an important receptor for progressive pain77.
Emerging drugs for the treatment of bladder storage dysfunction
Published in Expert Opinion on Emerging Drugs, 2022
Results from a phase II clinical trial (NCT01569438) with the selective, orally administered P2X3 receptor antagonist gefapixant (AF-219, MK-7264, and RO-4926219) showed a significant (p = 0.034) reduction in urinary urgency and a positive trend in the improvement of pain in patients with IC/BPS [35]. This drug showed efficacy in patients with refractory chronic cough [36] and recently, further controlled studies confirmed its efficacy on this condition. It was well tolerated except for disturbances in taste perception [37–39]. Gefapixant is the first-in-class clinically developed antagonist for the P2X3 subtype of trimeric ionotropic purinergic receptors, showing nanomolar potency for the human P2X3 homotrimeric channel and essentially no activity at related channels devoid of P2X3 subunits [40]. Also, eliapixant (BAY 1817080) is a P2X3 receptor antagonist, which is both highly potent and selective for P2X3 over other P2X subtypes in vitro, including P2X2/3 [41–43]. Its efficay, safety, and tolerability in refractory chronic cough have been tested in randomized, double-blind phase I and II studies [42,43]. Eliapixant was shown to be well tolerated with a minimal effect on taste perception and with a long plasma half-life. Davenport et al [41]. studied the effects of the drug on disorders associated with hypersensitive nerve fibers in different relevant rodent models. They showed that the drug reduced inflammatory pain and also provided the first in vivo experimental evidence that P2X3 antagonism reduces neurogenic inflammation.