TRPs in Pain Sensation

Jardín, Isaac; López, José J.; Diez, Raquel; Sánchez-Collado, José; Cantonero, Carlos; Albarrán, Letizia; Woodard, Geoffrey E.; Redondo, Pedro C.; Salido, Ginés M.; Smani, Tarik; Rosado, Juan A.

doi:10.3389/fphys.2017.00392

Cited by 120 publications

(92 citation statements)

References 146 publications

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“…In this study, we focus specifically upon one target for analgesia, the Transient Receptor Potential ion channel TRPV1. Several members of the TRP superfamily of non-selective cation channels have been identified both as nociceptive receptors for pungent plant compounds (e.g., capsaicin, allicin, menthol) and as targets for cannabinoids [31][32][33][34][35][36][37][38][39][40]. Both antagonism and agonism of the TRP channel are critical pharmacological approaches for pain management.…”

Section: Introductionmentioning

confidence: 99%

Myrcene and terpene regulation of TRPV1

et al. 2019

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Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through inactivation and chronic desensitization. Since plant-derived mixtures of cannabinoids and the Cannabis component myrcene have been suggested as pain therapeutics, we screened terpenes found in Cannabis for activity at TRPV1. We used inducible expression of TRPV1 to examine TRPV1-dependency of terpene-induced calcium flux responses. Terpenes contribute differentially to calcium fluxes via TRPV1 induced by Cannabis-mimetic cannabinoid/terpenoid mixtures. Myrcene dominates the TRPV1-mediated calcium responses seen with terpenoid mixtures. Myrcene-induced calcium influx is inhibited by the TRPV1 inhibitor capsazepine and Myrcene elicits TRPV1 currents in the wholecell patch-clamp configuration. TRPV1 currents are highly sensitive to internal calcium. When Myrcene currents are evoked, they are distinct from capsaicin responses on the basis of I max and their lack of shift to a pore-dilated state. Myrcene pre-application and residency at TRPV1 appears to negatively impact subsequent responses to TRPV1 ligands such as Cannabidiol, indicating allosteric modulation and possible competition by Myrcene. Molecular docking studies suggest a non-covalent interaction site for Myrcene in TRPV1 and identifies key residues that form partially overlapping Myrcene and Cannabidiol binding sites. We identify several non-Cannabis plantderived sources of Myrcene and other compounds targeting nociceptive TRPs using a data mining approach focused on analgesics suggested by non-Western Traditional Medical Systems. These data establish TRPV1 as a target of Myrcene and suggest the therapeutic potential of analgesic formulations containing Myrcene.

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Section: Introductionmentioning

confidence: 99%

Myrcene and terpene regulation of TRPV1

et al. 2019

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“…AEA can also activate TRPV1 channels [40]. TRPV1 is implicated in processing of various types of pain including neuropathic and inflammatory pain [182,[190][191][192]. TRPV1 channels are easily desensitized by TRPV1 agonists (e.g., capsaicin) [193].…”

Section: Modulation Of Endocannabinoids Under Neuropathic Pain Conditmentioning

confidence: 99%

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

Hossain

Ando

Unno

2020

IJMS

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Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in the brain. Alternative approaches have been developed to overcome this problem by selectively targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoids that may be locally synthesized on demand at sites where their actions are pertinent. Many preclinical studies have reported that these strategies are effective for treating neuropathic pain and produce no or minimal side effects. Recently, we observed that inhibition of degradation of a major endocannabinoid, 2-arachydonoylglycerol, can attenuate NOP following trigeminal nerve injury in mice. This review will discuss the above-mentioned alternative approaches that show potential for treating neuropathic pain including NOP.

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“…TRPV1 in the closed state (grey ribbon) was overlaid to the model. TRPV1 is closely related to various types of pain, including inflammatory pain, neuropathic pain, and cancer pain [90][91][92][93]. RhTx is the only centipede toxin that has been reported to activate the TRPV1 channel.…”

Section: Trpv1 Activatormentioning

confidence: 99%

Centipede Venom Peptides Acting on Ion Channels

Chu

Qiu

2020

Toxins

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Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of low-molecular-weight peptide toxins that have evolved to target voltage-gated ion channels to interfere with the central system of prey and produce pain or paralysis for efficient hunting. Peptide toxins usually contain several intramolecular disulfide bonds, which confer chemical, thermal and biological stability. In addition, centipede peptides generally have novel structures and high potency and specificity and therefore hold great promise both as diagnostic tools and in the treatment of human disease. Here, we review the centipede peptide toxins with reported effects on ion channels, including Nav, Kv, Cav and the nonselective cation channel polymodal transient receptor potential vanilloid 1 (TRPV1).

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TRPs in Pain Sensation

Cited by 120 publications

References 146 publications

Myrcene and terpene regulation of TRPV1

Myrcene and terpene regulation of TRPV1

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

Centipede Venom Peptides Acting on Ion Channels

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