Tramadol and Its Metabolite M1 Selectively Suppress Transient Receptor Potential Ankyrin 1 Activity, but Not Transient Receptor Potential Vanilloid 1 Activity

  title={Tramadol and Its Metabolite M1 Selectively Suppress Transient Receptor Potential Ankyrin 1 Activity, but Not Transient Receptor Potential Vanilloid 1 Activity},
  author={Kanako Miyano and Kouichiro Minami and Toru Yokoyama and Katsuya Ohbuchi and Takuhiro Yamaguchi and Satoshi Murakami and Seiji Shiraishi and Masahiro Yamamoto and Motohiro Matoba and Yasuhito Uezono},
  journal={Anesthesia \& Analgesia},
BACKGROUND:The transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1), which are expressed in sensory neurons, are polymodal nonselective cation channels that sense noxious stimuli. Recent reports showed that these channels play important roles in inflammatory, neuropathic, or cancer pain, suggesting that they may serve as attractive analgesic pharmacological targets. Tramadol is an effective analgesic that is widely used in clinical practice… 
Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways
It is suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.
Mammalian transient receptor potential TRPA1 channels: from structure to disease.
The current knowledge about the mammalian TRPA1 channel is reviewed, linking its unique structure, widely tuned sensory properties and complex regulation to its roles in multiple pathophysiological conditions.
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Mounting evidence now suggests that TRPV1 receptors on the central branches of dorsal root ganglion neurons in the spinal cord may play an important role in modulation of pain and nociceptive transmission.
The Inhibitory Effects of Tramadol on Muscarinic Receptor-Induced Responses in Xenopus Oocytes Expressing Cloned M3 Receptors
It is suggested that tramadol at clinically relevant concentrations inhibits M3 function via quinuclidinyl benzilate-binding sites, which may explain the modulation of neuronal function and the anticholinergic effects of tramadols.
CB(1) cannabinoid receptor stimulation modulates transient receptor potential vanilloid receptor 1 activities in calcium influx and substance P Release in cultured rat dorsal root ganglion cells.
It is suggested that CB(1) could inhibit either the capsaicin-induced Ca(2+) influx or the potentiation of capsaicIn-induced SPLI release by a long-term treatment with bradykinin through involvement of a cyclic-AMP-dependent PKA pathway.
The Effects of the Tramadol Metabolite O-Desmethyl Tramadol on Muscarinic Receptor-Induced Responses in Xenopus Oocytes Expressing Cloned M1 or M3 Receptors
O-desmethyl tramadol inhibits functions of M1 receptors but has little effect on those of M3 receptors, which may help to explain its neural function.
Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice
Results indicate that TRPV1 and TRPA1 could contribute to the development of thermal hyperalgesia and mechanical allodynia following cisplatin-induced painful neuropathy but that TRpV1 has a crucial role in cisPlatin- induced thermal hyper algesia in vivo.
Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain.
A novel mechanism through which bradykinin released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation is presented.
The Effects of Tramadol and Its Metabolite on Glycine, γ-Aminobutyric AcidA, and N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes
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Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances.
  • S. Hwang, H. Cho, U. Oh
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
It is shown that several products of lipoxygenases directly activate the capsaicin-activated channel in isolated membrane patches of sensory neurons, suggesting a novel signaling mechanism underlying the pain sensory transduction.