A Phase II, Randomized, Double-blind, Active Comparator, Parallel Group Study to Evaluate the Efficacy and Safety of K-285 Compared With Menthol Gel for the Treatment of Delayed Onset Muscle Soreness (DOMS) in the Lower Extremity

The purpose of this study to evaluate the efficacy and safety of K-285 compared with menthol gel for the treatment of delayed onset muscle soreness (DOMS) in the lower extremity.

Start Date15 Aug 2020

Sponsor / Collaborator

Kowa Research Institute, Inc.

NCT03712241 / CompletedPhase 1

A Phase I, Open-label, Randomized, 4-period Crossover Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of K-285 Compared With a Single Oral Dose of Indomethacin Capsule in Healthy Adult Volunteers

This study is to compare the PK parameters of multiple doses and applications of K-285 with a single dose of indomethacin capsule.

Start Date04 Oct 2018

Sponsor / Collaborator

Kowa Research Institute, Inc.

NCT02192203 / CompletedPhase 1

Safety Study to Investigate the Skin Sensitization Potential of MFC51123

This research study is being carried out to determine the possibility that a new medication causes allergic reactions. This new medication contains two active ingredients (diclofenac and menthol) together in a gel and is being developed to treat mild to moderate pain and inflammation, such as acute sport injuries, and sprains and strains. Approximately 240 participants will have the medication (gel) applied to the skin on a small area of the upper back for approximately 48-hour or 72-hour periods over the course of six weeks. Participation in this research study is voluntary, requiring participants to visit the study clinic on 17 occasions for about 45 minutes each visit. During the visits, doctors or trained staff members will examine the amount of redness, swelling, and other signs of irritation (if any) of the skin where the medication (gel) was applied.

Start Date01 Apr 2014

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with TRPA1 x TRPM8 x COX

100 Translational Medicine associated with TRPA1 x TRPM8 x COX

0 Patents (Medical) associated with TRPA1 x TRPM8 x COX

Literatures (Medical) associated with TRPA1 x TRPM8 x COX

01 Nov 2021·Food Research InternationalQ1 · AGRICULTURAL & FORESTRY SCIENCE

Chia oil prevents chemical and immune-mediated inflammatory responses in mice: Evidence for the underlying mechanisms

Q1 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Gonçalves, Elaine C D ; Raposo, Nádia R B ; Santos, Adara A ; Fadanni, Guilherme P ; Dutra, Rafael C ; Cavalli, Juliana ; Freitas, Mariana A

Chia (Salvia hispanica L.) is an herbaceous plant used as omega-3 polyunsaturated fatty acid (ω-3 PUFA) source that presents a range of beneficial effects on human health. Herein, it was used a chia oil containing over than 62% of α-linolenic acid (ALA), a compound widely related to anti-inflammatory actions. Chia oil effect was tested using paw edema and mechanical hyperalgesia induced by carrageenan, and ear edema induced by croton oil, histamine, and capsaicin. Croton oil was used in both preventive and therapeutic treatment schedules of chia oil while histamine and capsaicin were used only in preventive treatment schedule. Chia oil mechanism of action was investigated using nociception and paw edema response induced by intraplantar injection of acidified saline (ASIC activator), PGE₂ (prostaglandin pathway), cinnamaldehyde (TRPA1 activator), bradykinin (BK pathway), menthol (TRPM8 activator), and capsaicin (TRPV1 activator). Further, RT-PCR for inflammatory mediators (TRPA1, NF-κB, PPAR-γ, COX-2, IL-6, TNF, FPR2, FAAH, MAGL, and IL-12A) induced by carrageenan, NLRP3 inflammasome activation, and the cell viability were then accessed. Later, chia oil actions were evaluated in the experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Chia oil showed anti-edematogenic and anti-hyperalgesic effects when administered 1 h before pro-inflammatory stimulus - particularly carrageenan and croton oil. Moreover, chia oil upregulated the mRNA levels of COX-2 and formyl peptide receptor 2 (FPR2) while reduced IL-6 expression in the spinal cord of mice submitted to i.pl. injection of carrageenan. Interestingly, chia oil mediates antinociceptive effects in mice decreasing the nociceptive response induced by acidified saline, PGE₂, and cinnamaldehyde, but not by bradykinin, menthol, and capsaicin. On the EAE model, chia oil preventively administered attenuated EAE-induced motor deficits and mechanical hyperalgesia in mice, suggesting a valuable effect of chia oil supplementation in regulating inflammatory responses and some immune functions during immune-mediated inflammatory disorders (IMID). Nonetheless, additional reports will need to assess the effect of chia oil in well-controlled clinical trials performed in MS patients.

01 Jan 2014·Progress in Lipid ResearchQ1 · MEDICINE

TRP-channels as key integrators of lipid pathways in nociceptive neurons

Q1 · MEDICINE

Review

Author: Sisignano, Marco ; Geisslinger, Gerd ; Scholich, Klaus ; Bennett, David L H

TRP-channels are the most prominent family of ligand-gated ion channels for pain perception. In sensory neurons, TRPV1-V4, TRPA1 and TRPM8 are expressed and are responsible for the conversion of external stimuli to painful sensations. Under pathophysiological conditions, excessive activity of TRP-channels leads to mechanical allodynia and thermal hyperalgesia. Among the endogenous TRP-channel sensitizers, activators and inhibitors, more than 50 arachidonic acid- and linoleic acid-metabolites from the COX-, LOX- and CYP-pathways, as well as lysophospholipids and isoprenoids can be found. As a consequence, these lipids represent the vast majority of endogenous TRP-channel modulators in sensory neurons. Although the precise mechanisms of TRP-channel modulation by most lipids are still unknown, it became clear that lipids can either bind directly to the target TRP-channel or modulate TRP-channels indirectly by activating G-protein coupled receptors. Thus, TRP-channels seem to be key sensors for lipids, integrating and interpreting incoming signals from the different metabolic lipid pathways. Here, we discuss the specific properties of the currently known endogenous lipid-derived TRP-channel modulators concerning their ability to activate or inhibit TRP-channels, the molecular mechanisms of lipid/TRP-channel interactions and specific TRP-regulatory characteristics of the individual lipid families.

01 Jan 2012·PharmacologyQ4 · MEDICINE

Etodolac Blocks the Allyl Isothiocyanate-Induced Response in Mouse Sensory Neurons by Selective TRPA1 Activation

Q4 · MEDICINE

Article

Author: Nogawa, Masaki ; Kyoi, Takashi ; Inoue, Naoki ; Tajima, Koyuki ; Ito, Sunao

Background and Purpose: The excitability of nociceptors is modulated by the transient receptor potential cation channel, ankyrin subfamily, member 1 (TRPA1). We have previously reported that etodolac, a nonsteroidal anti-inflammatory drug, attenuates mechanical allodynia in a mouse model of neuropathic pain by a mechanism that is independent of cyclooxygenase inhibition. Here, we investigate the role of TRPA1 in the mechanism of the antinociceptive action of etodolac in vitro and in vivo. Experimental Approach: Ca2+ influx was measured in HEK-293 cells expressing mouse TRPA1 and in mouse dorsal root ganglion (DRG) neurons. The effect of etodolac on the nociceptive behavior induced in mice by the TRPA1 agonist allyl isothiocyanate (AITC) was also measured. Results: Etodolac induced Ca2+ influx in HEK-293 cells expressing mouse TRPA1 and in mouse DRG neurons. The Ca2+ influx induced by etodolac was inhibited by pretreatment with the TRPA1-specific antagonist HC-030031. In contrast, etodolac did not induce Ca2+ influx in cells expressing TRPV1, TRPV2 or TRPM8. In addition, pretreatment with etodolac inhibited the Ca2+ influx induced by AITC. Conclusion and Implication: Etodolac showed a selective TRPA1 agonist action, providing evidence that etodolac desensitizes nociceptors by the selective activation of TRPA1. Etodolac may be clinically useful in the treatment of neuropathic pain.

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