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Anti-Inflammatory Properties of Bioactive Compounds from Medicinal Plants
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Health Benefits of Secondary Phytocompounds from Plant and Marine Sources, 2021
Muhammad Imran, Abdur Rauf, Anees Ahmed Khalil, Saud Bawazeer, Seema Patel, Zafar Ali Shah
Hemp (Cannabis sativa) phenolics curtailed IBD (inflammatory bowel disease) and significantly protected against inflammatory ailments [5]. In LPS-stimulated murine peritoneal macrophages, non-psychotropic phytocannabinoid Δ9-tetrahydrocannabivarin (THCV) down-regulated the over-expression of iNOS, COX-2 and IL-1β proteins. Additionally, THCV countered LPS-induced progression of CB1 receptors, without alteration in mRNA expression of TRPV2, CB2, and TRPV4. In both unstimulated and LPS-challenged macrophages, other transient receptor potential (TRP) channels (specifically, TRPV1, TRPA1, TRPV3 andTRPM8) were unnoticeable. Conclusively, nitrite formation in macrophages was inhibited by THCV-via CB2 receptor activation. This phytocannabinoid down-regulated CB1, but not CB2 or mRNA expression of transient receptor potential channel [57]. Cannabidiol (5 µM) had modest effectiveness on TNF-α, IL-10, nitrotyrosine, iNOS, and Nrf-2. Progression of Bcl-2 and down-regulation of Bax and cleaved caspase-3 was noticed in cannabidiol-treated cells, whereas no impact was prompted by cannabinoid receptor-1 and 2 antagonists [21].
Pharmacological Treatment Approaches
Published in Andrea Kohn Maikovich-Fong, Handbook of Psychosocial Interventions for Chronic Pain, 2019
Catherine G. Derington, David K. Choi, Katy E. Trinkley
At the site of injury, neurotransmitters and chemicals act on specific receptors (called “nociceptors”) to mediate pain, including substance P, calcitonin gene-related peptide, bradykinin, nerve growth factor, prostaglandins, thromboxanes, leukotrienes, endocannabinoids, neurotrophins, cytokines/chemokines (e.g., interleukin-1β, interleukin-6, and tumor necrosis factor α), extracellular proteases, and protons. These chemicals may be released by inflammatory cells, cells that are damaged, or in response to a chemical or mechanical stimulus. The nerves that sense and respond to a pain stimulus express one or more nociceptors that are able to recognize and initiate the transmission of the pain signal to the central nervous system (spinal cord and brain) (Basbaum, Bautista, Scherrer, & Julius, 2009; Julius & Basbaum, 2001). Common nociceptors include TRPV1 (heat and mechanical stimuli), TRPV2 (heat and osmotic stretch), TRPM8 (cold stimuli), and TRPA1 (mechanical, cold, and chemical stimuli), among many others. Different forms and types of voltage-gated sodium and potassium channels transmit pain along nerve fibers to the spinal cord and brain. Voltage-gated calcium channels allow for the release of neurotransmitters at the end of nerves to send pain signals to other nerves.
Inflammatory Responses Acquired Following Environmental Exposures Are Involved in Pathogenesis of Musculoskeletal Pain
Published in Kohlstadt Ingrid, Cintron Kenneth, Metabolic Therapies in Orthopedics, Second Edition, 2018
Ritchie C. Shoemaker, James C. Ryan
At one time substance P was called capsaicin; its receptor TRPV1, is a nociceptive-specific ion channel [94]. This ion channel is activated by thermal injury and acidification as well. Other TRP ion channels are TRPV2, TRPV3, TRPV4, TRPM8 and TRPA1.Toxins [95] known to induce TRPV1 activation include scorpion venom, botulinum neurotoxin, spider toxin (NB: species not identified), ciguatoxin and brevetoxins. Vanillotoxins from a tarantula activate TRPV1 “via interaction with a region of TRPV1 that is homologous to voltage dependent ion channels.”
What is new about mild temperature sensing? A review of recent findings
Published in Temperature, 2019
Miriam García-Ávila, León D. Islas
The channels TRPV1, TRPV2, TRPV4, TRPM3, and TRPM8 channels, have been implicated in the perception of pain in humans, because these channels are expressed in sensory nerve endings [41]. There is also the possibility that thermoTRP channels are involved in diseases like respiratory disorders (TRPV1, TRPV4, TRPA1, and TRPM8), because the human respiratory tract is innervated by sensory fibers which are activated by irritant stimuli [41]. Other thermoTRPs are also related to diseases like diabetes, for example, TRPM2, TRPM3, TRPM4/M5, and TRPA1, which are expressed in beta-cells and are directly involved in insulin secretion [42]. It has been hypothesized that some thermoTRP channels (TRPV1, TRPV2, TRPV4, TRPM2, TRPM4, TRPM8 and TRPM8) could be involved in various kinds of cancers [43,44]. Recently TRPV2 and TPV4 were implicated in mediating human melanoma cell death [45], but the relation between cancer and TRP-channels is still controversial. One thermoTRP channel in the brain, TRPC5 which is highly expressed in hippocampus and amygdala, has been proposed as a therapeutic target for anxiety [46].
Investigational drugs in early phase clinical trials targeting thermotransient receptor potential (thermoTRP) channels
Published in Expert Opinion on Investigational Drugs, 2020
Asia Fernández-Carvajal, Rosario González-Muñiz, Gregorio Fernández-Ballester, Antonio Ferrer-Montiel
Despite of its presence in various tissues and organs, the physiological role of TRPV2 has not been completely elucidated. Due to its stretch-dependent properties, this channel has been proposed to act as a mechanosensor and/or osmosensor [23]. TRPV2 appears involved in the regulation of intestinal motility [24], in innate and adaptive immune responses [25], and in early osteoclastogenesis [26]. TRPV2 channels expressed in cardiomyocytes could play a significant role in the regulation of intracellular Ca2+ and, therefore, in cardiac contractility [27]. In the endocrine system, TRPV2 seems to participate in the autocrine feedforward action of insulin in pancreatic β-cells [28].
A molecular perspective on identifying TRPV1 thermosensitive regions and disentangling polymodal activation
Published in Temperature, 2023
Dustin D. Luu, Aerial M. Owens, Mubark D. Mebrat, Wade D. Van Horn
Chimeric proteins are commonly used to identify functional regions in proteins. One such chimeric study swapped regions of rTRPV1 with corresponding rTRPV2 regions [112]. Physiologically TRPV2 likely functions as a redox sensor. Biophysically, TRPV2 has complex heat activation phenotypes that are ortholog-dependent. rTRPV2 is heat-activated at non-physiological temperatures (>50 °C), and hTRPV2 is reported to be temperature insensitive [119]. rTRPV1–rTRPV2 transmembrane domain (S1-S6) chimeras offered no apparent differences in the thermosensitivity (112]. While the results show slightly altered temperature activation, it is unclear if the origins arose from the TMD or the terminal domains. Additional chimeras, where the entire N- or C-terminal domains were swapped between TRPV1 and TRPV2 resulted in nonfunctional channels [112]. Considering there are several TRPV1 studies that have successfully manipulated parts of the N- or C-terminal domains and still retained function [114,117,120], the nonfunctional N-terminal or C-terminal chimeras could be trafficking deficient or stabilized in a closed state. Functional TRPV1-TRPV2 chimeras were made by swapping smaller subsections of either the rTRPV1 N-terminal domain ankyrin repeat domain (ARD, rat 1–357) or the membrane-proximal domain (MPD, rat 358–434) [112]. The rTRPV2[TRPV1-MPD] chimera displayed a 65% reduction in thermosensitivity, with 112]. On the other hand, the 112]. The ~30 kcal/mol increase in thermosensitivity over WT TRPV1 was isolated to ARD 5–6 [112], and the change in 112].