Expression of transient receptor potential ankyrin 1 (TRPA1) in the rat trigeminal sensory afferents and spinal dorsal horn

2009 ◽  
Vol 518 (5) ◽  
pp. 687-698 ◽  
Author(s):  
Yun Sook Kim ◽  
Jae Youn Son ◽  
Tae Heon Kim ◽  
Sang Kyoo Paik ◽  
Yi Dai ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Sensory Afferents ◽  
Spinal Dorsal ◽  
Transient Receptor

Acetaminophen Metabolite N-Acylphenolamine Induces Analgesia via Transient Receptor Potential Vanilloid 1 Receptors Expressed on the Primary Afferent Terminals of C-fibers in the Spinal Dorsal Horn

2017 ◽  
Vol 127 (2) ◽  
pp. 355-371 ◽  
Author(s):  
Nobuko Ohashi ◽  
Daisuke Uta ◽  
Mika Sasaki ◽  
Masayuki Ohashi ◽  
Yoshinori Kamiya ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Direct Application ◽  
Transient Receptor Potential Vanilloid ◽  
Analgesic Effects ◽  
Spinal Dorsal ◽  
C Fibers ◽  
Transient Receptor

Abstract Background The widely used analgesic acetaminophen is metabolized to N-acylphenolamine, which induces analgesia by acting directly on transient receptor potential vanilloid 1 or cannabinoid 1 receptors in the brain. Although these receptors are also abundant in the spinal cord, no previous studies have reported analgesic effects of acetaminophen or N-acylphenolamine mediated by the spinal cord dorsal horn. We hypothesized that clinical doses of acetaminophen induce analgesia via these spinal mechanisms. Methods We assessed our hypothesis in a rat model using behavioral measures. We also used in vivo and in vitro whole cell patch-clamp recordings of dorsal horn neurons to assess excitatory synaptic transmission. Results Intravenous acetaminophen decreased peripheral pinch-induced excitatory responses in the dorsal horn (53.1 ± 20.7% of control; n = 10; P < 0.01), while direct application of acetaminophen to the dorsal horn did not reduce these responses. Direct application of N-acylphenolamine decreased the amplitudes of monosynaptic excitatory postsynaptic currents evoked by C-fiber stimulation (control, 462.5 ± 197.5 pA; N-acylphenolamine, 272.5 ± 134.5 pA; n = 10; P = 0.022) but not those evoked by stimulation of Aδ-fibers. These phenomena were mediated by transient receptor potential vanilloid 1 receptors, but not cannabinoid 1 receptors. The analgesic effects of acetaminophen and N-acylphenolamine were stronger in rats experiencing an inflammatory pain model compared to naïve rats. Conclusions Our results suggest that the acetaminophen metabolite N-acylphenolamine induces analgesia directly via transient receptor potential vanilloid 1 receptors expressed on central terminals of C-fibers in the spinal dorsal horn and leads to conduction block, shunt currents, and desensitization of these fibers.

scholarly journals Analgesic Effect of Acetaminophen: A Review of Known and Novel Mechanisms of Action

2020 ◽  
Vol 11 ◽  
Author(s):  
Nobuko Ohashi ◽  
Tatsuro Kohno
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Nociceptive Transmission ◽  
Spinal Dorsal ◽  
C Fibers ◽  
Trpv1 Receptors ◽  
The Brain

Acetaminophen is one of the most commonly used analgesic agents for treating acute and chronic pain. However, its metabolism is complex, and its analgesic mechanisms have not been completely understood. Previously, it was believed that acetaminophen induces analgesia by inhibiting cyclooxygenase enzymes; however, it has been considered recently that the main analgesic mechanism of acetaminophen is its metabolization to N-acylphenolamine (AM404), which then acts on the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid 1 receptors in the brain. We also recently revealed that the acetaminophen metabolite AM404 directly induces analgesia via TRPV1 receptors on terminals of C-fibers in the spinal dorsal horn. It is known that, similar to the brain, the spinal dorsal horn is critical to pain pathways and modulates nociceptive transmission. Therefore, acetaminophen induces analgesia by acting not only on the brain but also the spinal cord. In addition, acetaminophen is not considered to possess any anti-inflammatory activity because of its weak inhibition of cyclooxygenase (COX). However, we also revealed that AM404 induces analgesia via TRPV1 receptors on the spinal dorsal horn in an inflammatory pain rat model, and these analgesic effects were stronger in the model than in naïve rats. The purpose of this review was to summarize the previous and new issues related to the analgesic mechanisms of acetaminophen. We believe that it will allow clinicians to consider new pain management techniques involving acetaminophen.

scholarly journals Enhanced insulin clearance in mice lacking TRPM8 channels

2013 ◽  
Vol 305 (1) ◽  
pp. E78-E88 ◽  
Author(s):  
Daniel D. McCoy ◽  
Ligang Zhou ◽  
Anh-Khoi Nguyen ◽  
Alan G. Watts ◽  
Casey M. Donovan ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Blood Glucose Concentration ◽  
Serum Insulin ◽  
Receptor Potential ◽  
Insulin Clearance ◽  
Sensory Innervation ◽  
Insulin Degrading Enzyme ◽  
Sensory Afferents ◽  
Transient Receptor ◽  
Hepatic Portal

Blood glucose concentration is tightly regulated by the rate of insulin secretion and clearance, a process partially controlled by sensory neurons serving as metabolic sensors in relevant tissues. The activity of these neurons is regulated by the products of metabolism which regulate transmitter release, and recent evidence suggests that neuronally expressed ion channels of the transient receptor potential (TRP) family function in this critical process. Here, we report the novel finding that the cold and menthol-gated channel TRPM8 is necessary for proper insulin homeostasis. Mice lacking TRPM8 respond normally to a glucose challenge while exhibiting prolonged hypoglycemia in response to insulin. Additionally, Trpm8 -/- mice have increased rates of insulin clearance compared with wild-type animals and increased expression of insulin-degrading enzyme in the liver. TRPM8 channels are not expressed in the liver, but TRPM8-expressing sensory afferents innervate the hepatic portal vein, suggesting a TRPM8-mediated neuronal control of liver insulin clearance. These results demonstrate that TRPM8 is a novel regulator of serum insulin and support the role of sensory innervation in metabolic homeostasis.

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