TRP channels in cancer pain

Almeida, Amanda Spring de; Bernardes, Laura de Barros; Trevisan, Gabriela

doi:10.1016/j.ejphar.2021.174185

Cited by 45 publications

(23 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This led to the belief that single modality activation of TRPV1 could not be achieved 25 , despite the fact that in electrophysiology studies RTx alone elicits channel open probabilities reaching 1 and allows for conduction of large organic cations 26 , 27 . Understanding the conformational landscape of RTx-dependent TRPV1 gating is not only fundamentally important, but it also has potential therapeutic impact; RTx is currently being evaluated in phase III clinical trials for pain associated with advanced cancer and arthritis of the knee, with positive preliminary results 28 – 30 . This raises the promise that RTx could provide a non-opioid solution to intractable chronic inflammatory pain.…”

Section: Introductionmentioning

confidence: 99%

Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis

et al. 2022

View full text Add to dashboard Cite

Single particle cryo-EM often yields multiple protein conformations within a single dataset, but experimentally deducing the temporal relationship of these conformers within a conformational trajectory is not trivial. Here, we use thermal titration methods and cryo-EM in an attempt to obtain temporal resolution of the conformational trajectory of the vanilloid receptor TRPV1 with resiniferatoxin (RTx) bound. Based on our cryo-EM ensemble analysis, RTx binding to TRPV1 appears to induce intracellular gate opening first, followed by selectivity filter dilation, then pore loop rearrangement to reach the final open state. This apparent conformational wave likely arises from the concerted, stepwise, additive structural changes of TRPV1 over many subdomains. Greater understanding of the RTx-mediated long-range allostery of TRPV1 could help further the therapeutic potential of RTx, which is a promising drug candidate for pain relief associated with advanced cancer or knee arthritis.

show abstract

Section: Introductionmentioning

confidence: 99%

Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Furthermore, both neuron types produced Ca 2+ responses to activators of transient receptor potential (TRP) channels, such as capsaicin (an activator of TRPV1 channels) and allyl isothiocyanate (AITC; an activator of TRPA1 channels) [ 68 ]. Because TRP channels play a key role in pain detection [ 69 ], this finding raises hope that the neuron-differentiated hDPSCs can be used in a pain detection network as a human peripheral pain model system.…”

Section: Other Topics For Pain Reliefmentioning

confidence: 99%

Dorsolateral prefrontal cortex sensing analgesia

2022

View full text Add to dashboard Cite

Chronic pain often has an unknown cause, and many patients with chronic pain learn to accept that their pain is incurable and pharmacologic treatments are only temporarily effective. Complementary and integrative health approaches for pain are thus in high demand. One such approach is soft touch, e.g., adhesion of pyramidal thorn patches in a pain region. The effects of patch adhesion on pain relief have been confirmed in patients with various types of pain. A recent study using near-infrared spectroscopy revealed that the dorsolateral prefrontal cortex (DLPFC), especially the left side, is likely to be inactivated in patients experiencing pain relief during patch treatment. Mindfulness meditation is another well-known complementary and integrative approach for achieving pain relief. The relation between pain relief due to mindfulness meditation and changes in brain regions, including the DLPFC, has long been examined. In the present review article, we survey the literature describing the effects of the above-mentioned complementary and integrative treatments on pain relief, and outline the important brain regions, including the DLPFC, that are involved in analgesia. We hope that the present article will provide clues to researchers who hope to advance neurosensory treatments for pain relief without medication.

show abstract

“…In addition to the currently approved drugs for neuraxial administration, a plethora of agents have been approved for other indications/routes of administration but are used offlabel for spinal or epidural injections. With respect to local anesthetics, possible future innovations may comprise the use of agents that have hitherto not been used neuraxially on a large scale, such as liposomal bupivacaine, butamben, Gabapentin [220] Substance P-saporin [221] Adenosine [222] CGX-1160 [223] Ketorolac [224] Xen2174 [225] Calcitonin [226] Contulakin-G [227] Octreotide [228] Muscimol [229] HTX-011 [230] Resiniferatoxin [231] Droperidol [113] or mepivacaine [3,214,215]. Furthermore, novel sodium channel blockers such as neosaxitoxin [216] or modalityselective blocking agents could possibly gain interest for neuraxial administration in the future [217].…”

Section: New Developments In Neuraxial Drug Administrationmentioning

confidence: 99%

The Options for Neuraxial Drug Administration

et al. 2022

View full text Add to dashboard Cite

Neuraxial drug administration, i.e., the injection of drugs into the epidural or intrathecal space to produce anesthesia or analgesia, is a technique developed more than 120 years ago. Today, it still is widely used in daily practice in anesthesiology and in acute and chronic pain therapy. A multitude of different drugs have been introduced for neuraxial injection, only a part of which have obtained official approval for that indication. A broad understanding of the pharmacology of those agents is essential to the clinician to utilize them in a safe and efficient manner. In the present narrative review, we summarize current knowledge on neuraxial anatomy relevant to clinical practice, including pediatric anatomy. Then, we delineate the general pharmacology of neuraxial drug administration, with particular attention to specific aspects of epidural and intrathecal pharmacokinetics and pharmacodynamics. Furthermore, we describe the most common clinical indications for neuraxial drug administration, including the perioperative setting, obstetrics, and chronic pain. Then, we discuss possible neurotoxic effects of neuraxial drugs, and moreover, we detail the specific properties of the most commonly used neuraxial drugs that are relevant to clinicians who employ epidural or intrathecal drug administration, in order to ensure adequate treatment and patient safety in these techniques. Finally, we give a brief overview on new developments in neuraxial drug therapy.

show abstract

TRP channels in cancer pain

Cited by 45 publications

References 119 publications

Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis

Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis

Dorsolateral prefrontal cortex sensing analgesia

The Options for Neuraxial Drug Administration

Contact Info

Product

Resources

About