scholarly journals A Proposed Molecular Mechanism for Physical Analgesia in Chronic Pain

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Norio Saito ◽  
Rei Shima ◽  
Yurika Yamada ◽  
Masaru Nagaoka ◽  
Etsuro Ito ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Relief ◽  
Molecular Mechanism ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Pain Treatment ◽  
Receptor Potential ◽  
Alternative Methods ◽  
Heavy Burden ◽  
Transient Receptor

Although pain is indispensable for survival, chronic pain places a heavy burden on humans. As the efficacy of opioid treatment is limited, the development of alternative methods of pain relief without medication is desirable. Recently, we have developed a novel method of physical analgesia using an adhesive “pyramidal thorn patch.” When we apply about 3 trials of these patches on the skin of a pain region, the pain region moves toward the spinal cord like a “cutaneous rabbit,” and finally, the pain vanishes. In the present review, we propose a molecular mechanism for this analgesic method or pain relief following application of the pyramidal thorn patch where firstly the mechanoreceptors and their related nerves under the skin are activated in response to touch. Transient receptor potential (TRP) channels serve as mechanosensitive channels within these mechanoreceptors. We further propose that activation of the nerves connected with the mechanoreceptors releases oxytocin, which has an antinociceptive function and activates TRP channels to hyperpolarize the pain signal nerves. We believe that our system will pave the way for alternative pain treatment.

scholarly journals Preface by the Editor

2013 ◽  
Vol 6 (1) ◽  
pp. 7-7
Author(s):  
Arpad Szallasi
Keyword(s):  
Clinical Trials ◽  
Pain Relief ◽  
Small Molecule ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Analgesic Drugs ◽  
The Past ◽  
Pharmacological Targets ◽  
Transient Receptor

With over 600 reviews, Transient Receptor Potential (TRP) channels arguably represent today’s most extensively reviewed pharmacological targets. The literature on TRP channels is vast and still growing: it has exploded from a mere 21 papers in 1995 to over 2,000 in the past two years. In the past fifteen years, the field had shown spectacular progress. From the cloning of the vanilloid (capsaicin) recep a novel class of analgesic agents.tor TRPV1 in 1997 it has taken only a decade for the first small molecule TRPV1 antagonists to enter clinical trials as So why to add another review collection to this already overwhelming body of literature? First, new therapeutic tar-gets are emerging (e.g. TRPA1 and TRPV3) that look even more promising than TRPV1. Second, even the most studied TRP channel, TRPV1, continues to surprise. One might ar-gue that we are still at the beginning of the long and arduous road to obtain clinically useful analgesic drugs targeting TRP channels. It remains to be discovered if TRP channels are really Targets for Pain Relief, but it has already been clear that Bernd Nilius was right in calling TRP channels “Truly Remarkable Proteins.”

scholarly journals TRP Channel Cooperation for Nociception: Therapeutic Opportunities

2021 ◽  
Vol 61 (1) ◽  
pp. 655-677
Author(s):  
Dorien Bamps ◽  
Joris Vriens ◽  
Jan de Hoon ◽  
Thomas Voets
Keyword(s):  
Chronic Pain ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Pain Treatment ◽  
Treatment Options ◽  
Receptor Potential ◽  
Current Treatment ◽  
Trp Channel ◽  
Current Status ◽  
Number Of Patients

Chronic pain treatment remains a sore challenge, and in our aging society, the number of patients reporting inadequate pain relief continues to grow. Current treatment options all have their drawbacks, including limited efficacy and the propensity of abuse and addiction; the latter is exemplified by the ongoing opioid crisis. Extensive research in the last few decades has focused on mechanisms underlying chronic pain states, thereby producing attractive opportunities for novel, effective and safe pharmaceutical interventions. Members of the transient receptor potential (TRP) ion channel family represent innovative targets to tackle pain sensation at the root. Three TRP channels, TRPV1, TRPM3, and TRPA1, are of particular interest, as they were identified as sensors of chemical- and heat-induced pain in nociceptor neurons. This review summarizes the knowledge regarding TRP channel–based pain therapies, including the bumpy road of the clinical development of TRPV1 antagonists, the current status of TRPA1 antagonists, and the future potential of targeting TRPM3.

scholarly journals Transient Receptor Potential Channels and Botulinum Neurotoxins in Chronic Pain

2021 ◽  
Vol 14 ◽  
Author(s):  
Eun Jin Go ◽  
Jeongkyu Ji ◽  
Yong Ho Kim ◽  
Temugin Berta ◽  
Chul-Kyu Park
Keyword(s):  
Chronic Pain ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Analgesic Effects ◽  
Botulinum Neurotoxins ◽  
Potential Channels ◽  
Transient Receptor ◽  
And Function

Pain afflicts more than 1.5 billion people worldwide, with hundreds of millions suffering from unrelieved chronic pain. Despite widespread recognition of the importance of developing better interventions for the relief of chronic pain, little is known about the mechanisms underlying this condition. However, transient receptor potential (TRP) ion channels in nociceptors have been shown to be essential players in the generation and progression of pain and have attracted the attention of several pharmaceutical companies as therapeutic targets. Unfortunately, TRP channel inhibitors have failed in clinical trials, at least in part due to their thermoregulatory function. Botulinum neurotoxins (BoNTs) have emerged as novel and safe pain therapeutics because of their regulation of exocytosis and pro-nociceptive neurotransmitters. However, it is becoming evident that BoNTs also regulate the expression and function of TRP channels, which may explain their analgesic effects. Here, we summarize the roles of TRP channels in pain, with a particular focus on TRPV1 and TRPA1, their regulation by BoNTs, and briefly discuss the use of BoNTs for the treatment of chronic pain.

Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses

2011 ◽  
Vol 110 (3) ◽  
pp. 789-798 ◽  
Author(s):  
Kaori Ono ◽  
Masako Tsukamoto-Yasui ◽  
Yoshiko Hara-Kimura ◽  
Naohiko Inoue ◽  
Yoshihito Nogusa ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Low Frequency ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Intragastric Administration ◽  
Brown Adipose ◽  
Reflex Arc ◽  
Transient Receptor

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

scholarly journals Functional Interaction among KCa and TRP Channels for Cardiovascular Physiology: Modern Perspectives on Aging and Chronic Disease

2019 ◽  
Vol 20 (6) ◽  
pp. 1380 ◽  
Author(s):  
Erik Behringer ◽  
Md Hakim
Keyword(s):  
Blood Flow ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
The Body ◽  
Cardiovascular Physiology ◽  
Treatment And Prevention ◽  
Kca Channels ◽  
Age Related ◽  
Transient Receptor

Effective delivery of oxygen and essential nutrients to vital organs and tissues throughout the body requires adequate blood flow supplied through resistance vessels. The intimate relationship between intracellular calcium ([Ca2+]i) and regulation of membrane potential (Vm) is indispensable for maintaining blood flow regulation. In particular, Ca2+-activated K+ (KCa) channels were ascertained as transducers of elevated [Ca2+]i signals into hyperpolarization of Vm as a pathway for decreasing vascular resistance, thereby enhancing blood flow. Recent evidence also supports the reverse role for KCa channels, in which they facilitate Ca2+ influx into the cell interior through open non-selective cation (e.g., transient receptor potential; TRP) channels in accord with robust electrical (hyperpolarization) and concentration (~20,000-fold) transmembrane gradients for Ca2+. Such an arrangement supports a feed-forward activation of Vm hyperpolarization while potentially boosting production of nitric oxide. Furthermore, in vascular types expressing TRP channels but deficient in functional KCa channels (e.g., collecting lymphatic endothelium), there are profound alterations such as downstream depolarizing ionic fluxes and the absence of dynamic hyperpolarizing events. Altogether, this review is a refined set of evidence-based perspectives focused on the role of the endothelial KCa and TRP channels throughout multiple experimental animal models and vascular types. We discuss the diverse interactions among KCa and TRP channels to integrate Ca2+, oxidative, and electrical signaling in the context of cardiovascular physiology and pathology. Building from a foundation of cellular biophysical data throughout a wide and diverse compilation of significant discoveries, a translational narrative is provided for readers toward the treatment and prevention of chronic, age-related cardiovascular disease.

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