Irritant Volatile Anesthetics Induce Neurogenic Inflammation Through TRPA1 and TRPV1 Channels in the Isolated Mouse Trachea

Kichko, Tatjana I.; Niedermirtl, Florian; Leffler, Andreas; Reeh, Peter W.

doi:10.1213/ane.0000000000000568

Cited by 29 publications

(30 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, isoflurane was shown to inhibit muscarinic receptors (14-16), to disrupt muscarinic receptor - G protein coupling (16-18) and to inhibit gastrointestinal motility in rats following even a brief exposure (19). In addition, there is accumulating evidence that inhalation anesthetics act on several TRP channels, such as TRPV1, TRPA1 and TRPM8 (20-22), although canonical TRPC channels have not been yet investigated in this respect. It should be noted that sevoflurane at clinically relevant concentrations strongly inhibited thapsigargin-induced current in ventricular myocytes.…”

Section: Introductionmentioning

confidence: 99%

Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions

Dryn

Luo

Melnyk

et al. 2018

European Journal of Pharmacology

View full text Add to dashboard Cite

Gastrointestinal tract motility may be demoted significantly after surgery operations at least in part due to anaesthetic agents, but there is no comprehensive explanation of the molecular mechanism(s) of such adverse effects. Anesthetics are known to interact with various receptors and ion channels including several subtypes of transient receptor potential (TRP) channels. Two members of the canonical subfamily of TRP channels (TRPC), TRPC4 and TRPC6 are Ca2+-permeable cation channels involved in visceral smooth muscle contractility induced by acetylcholine, the primary excitatory neurotransmitter in the gut. In the present study, we aimed to study the effect of anesthetics on muscarinic receptor-mediated excitation and contraction of intestinal smooth muscle. Here we show that muscarinic cation current (mICAT) mediated by TRPC4 and TRPC6 channels in mouse ileal myocytes was strongly inhibited by isoflurane (0.5mM), one of the most commonly used inhalation anaesthetics. Carbachol-activated mICAT was reduced by 63 ± 11% (n=5), while GTPγS-induced (to bypass muscarinic receptors) current was inhibited by 44 ± 9% (n=6). Furthermore, carbachol-induced ileum and colon contractions were inhibited by isoflurane by about 30%. We discuss the main sites of isoflurane action, which appear to be G-proteins and muscarinic receptors, rather than TRPC4/6 channels. These results contribute to our better understanding of the signalling pathways affected by inhalation anaesthetics, which may cause ileus, and thus may be important for the development of novel treatment strategies during postoperative recovery.

show abstract

Section: Introductionmentioning

confidence: 99%

Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions

Dryn

Luo

Melnyk

et al. 2018

European Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…The neuroinflammation produced by activation of transient receptor potential A1 (TRPA1) and V1 (TRPV1) channels on primary afferent fibers or peripheral nociceptors was thought to be involved in part in hyperalgesia induced by low doses of volatile irritant anesthetics such as isoflurane and desflurane. 13,41,42 The TRPA1 channel, a nonselective cation channel, is Figure 7. The effects of sevoflurane and desflurane on the sedation and pain thresholds for thermal stimuli.…”

Section: Discussionmentioning

confidence: 99%

Effects of sevoflurane and desflurane on the nociceptive responses of substantia gelatinosa neurons in the rat spinal cord dorsal horn: An in vivo patch-clamp analysis

et al. 2020

View full text Add to dashboard Cite

Background: Volatile anesthetics suppress noxiously evoked activity in the spinal dorsal horn, which could contribute in part to analgesia, immobility. Modulation of excitatory and inhibitory synaptic transmission in substantia gelatinosa neurons could lead to the suppression of dorsal horn activity; however, this phenomenon has not yet been investigated fully. Methods: In urethane-anesthetized rats, extracellular activity of dorsal horn neurons (action potentials) and excitatory/ inhibitory postsynaptic currents in substantia gelatinosa neurons were recorded using extracellular and in vivo patch-clamp techniques, respectively, to assess the spontaneous and the noxious-evoked activity. Sevoflurane or desflurane at concentrations ranging from 0.1 to 2 minimum alveolar concentration was administered by inhalation. Hot-and cold-plate tests were performed to assess nociceptive responses during the inhalation of volatile anesthetics at lower anesthetic doses (0.1-0.5 minimum alveolar concentration). Results: At anesthetic doses (1 and 2 minimum alveolar concentration), both sevoflurane and desflurane decreased the frequency of action potentials in the dorsal horn and the activities of excitatory postsynaptic currents in substantia gelatinosa neurons during pinch stimulation and decreased the activities of spontaneous and miniature excitatory postsynaptic currents. Inhibition of the frequencies was more prominent than that of amplitudes in spontaneous and miniature excitatory postsynaptic currents at these anesthetic doses. However, at subanesthetic doses (0.1 and 0.2 minimum alveolar concentration), desflurane facilitated action potentials and excitatory postsynaptic currents. Inhibitory postsynaptic currents were inhibited by both anesthetics at anesthetic doses (1 and 2 minimum alveolar concentration). Hot-or cold-plate tests showed hyperalgesic effects of desflurane at subanesthetic doses (0.1 and 0.2 minimum alveolar concentration) and a dose-dependent analgesic effect of sevoflurane. Conclusions: Sevoflurane and desflurane at anesthetic doses suppressed dorsal horn activity mainly via inhibition of excitatory postsynaptic currents in substantia gelatinosa neurons, which would contribute to their analgesic properties. Presynaptic mechanisms were likely in excitatory postsynaptic currents inhibition. Desflurane but not sevoflurane may have a hyperalgesic effect at subanesthetic doses.

show abstract

“…Anesthesia induces post-anesthetic distress with a variety of causes. Isoflurane has a pungent odor [54] and induces irritant effects in the airways by activating nociceptive ion channels [55,56]. In humans, the inhalation of isoflurane causes coughing and subjective sensations of burning as well as irritation [57].…”

Section: Plos Onementioning

confidence: 99%

Towards a fully automated surveillance of well-being status in laboratory mice using deep learning: Starting with facial expression analysis

et al. 2020

View full text Add to dashboard Cite

Assessing the well-being of an animal is hindered by the limitations of efficient communication between humans and animals. Instead of direct communication, a variety of parameters are employed to evaluate the well-being of an animal. Especially in the field of biomedical research, scientifically sound tools to assess pain, suffering, and distress for experimental animals are highly demanded due to ethical and legal reasons. For mice, the most commonly used laboratory animals, a valuable tool is the Mouse Grimace Scale (MGS), a coding system for facial expressions of pain in mice. We aim to develop a fully automated system for the surveillance of post-surgical and post-anesthetic effects in mice. Our work introduces a semi-automated pipeline as a first step towards this goal. A new data set of images of black-furred laboratory mice that were moving freely is used and provided. Images were obtained after anesthesia (with isoflurane or ketamine/xylazine combination) and surgery (castration). We deploy two pre-trained state of the art deep convolutional neural network (CNN) architectures (ResNet50 and InceptionV3) and compare to a third CNN architecture without pre-training. Depending on the particular treatment, we achieve an accuracy of up to 99% for the recognition of the absence or presence of post-surgical and/or post-anesthetic effects on the facial expression.

show abstract

Irritant Volatile Anesthetics Induce Neurogenic Inflammation Through TRPA1 and TRPV1 Channels in the Isolated Mouse Trachea

Cited by 29 publications

References 27 publications

Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions

Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions

Effects of sevoflurane and desflurane on the nociceptive responses of substantia gelatinosa neurons in the rat spinal cord dorsal horn: An in vivo patch-clamp analysis

Towards a fully automated surveillance of well-being status in laboratory mice using deep learning: Starting with facial expression analysis

Contact Info

Product

Resources

About