Vagus nerve is involved in the changes in body temperature induced by intragastric administration of 1,8-cineole via TRPM8 in mice

Urata, Tomomi; Mori, Nanako; Fukuwatari, Tsutomu

doi:10.1016/j.neulet.2017.04.018

Cited by 10 publications

(6 citation statements)

References 24 publications

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“…TRPM8 is a key channel for cold and pain perception [10,[43][44][45]. Previous studies reported the effectiveness of M8-B, a selective and potent TRPM8 antagonist [46][47][48], on cold nociceptors via TRPM8 by decreasing deep body temperature in Trpm8 +/+ mice and rats, but not in Trpm8 −/− mice, highlighting an on-target action [48]. Thus, in the present study, we explored whether M8-B could alleviate ocular pain associated with severe DED.…”

Section: Discussionmentioning

confidence: 89%

TRPM8: A Therapeutic Target for Neuroinflammatory Symptoms Induced by Severe Dry Eye Disease

Fakih

Baudouin

Goazigo

et al. 2020

IJMS

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Dry eye disease (DED) is commonly associated with ocular surface inflammation and pain. In this study, we evaluated the effectiveness of repeated instillations of transient receptor potential melastatin 8 (TRPM8) ion channel antagonist M8-B on a mouse model of severe DED induced by the excision of extra-orbital lacrimal and Harderian glands. M8-B was topically administered twice a day from day 7 until day 21 after surgery. Cold and mechanical corneal sensitivities and spontaneous ocular pain were monitored at day 21. Ongoing and cold-evoked ciliary nerve activities were next evaluated by electrophysiological multi-unit extracellular recording. Corneal inflammation and expression of genes related to neuropathic pain and inflammation were assessed in the trigeminal ganglion. We found that DED mice developed a cold allodynia consistent with higher TRPM8 mRNA expression in the trigeminal ganglion (TG). Chronic M8-B instillations markedly reversed both the corneal mechanical allodynia and spontaneous ocular pain commonly associated with persistent DED. M8-B instillations also diminished the sustained spontaneous and cold-evoked ciliary nerve activities observed in DED mice as well as inflammation in the cornea and TG. Overall, our study provides new insight into the effectiveness of TRPM8 blockade for alleviating corneal pain syndrome associated with severe DED, opening a new avenue for ocular pain management.

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Section: Discussionmentioning

confidence: 89%

TRPM8: A Therapeutic Target for Neuroinflammatory Symptoms Induced by Severe Dry Eye Disease

Fakih

Baudouin

Goazigo

et al. 2020

IJMS

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Section: Trpm8 Agonistsmentioning

confidence: 99%

“…Two different studies confirmed that eucalyptol (1,8-cineol, 3 ) is an effective tool to investigate the biology of TRP channels [28,29]. Thus, Urata et al established the relationship between thermoregulation and TRPM8 expression in the afferent vagal nerve [28]. In mice, intragastric and intravenous administration of 1,8-cineol (100 and 10 mg/kg, respectively) increased the temperature of the intrascapular brown adipose tissue and colon, whereas, previous treatment with a TRPM8 antagonist, M8-B, inhibited these responses.…”

Section: Trpm8 Agonistsmentioning

confidence: 99%

Recent Progress in TRPM8 Modulation: An Update

González‐Muñiz

Bonache

Martín-Escura

et al. 2019

IJMS

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The transient receptor potential melastatin subtype 8 (TRPM8) is a nonselective, multimodal ion channel, activated by low temperatures (<28 °C), pressure, and cooling compounds (menthol, icilin). Experimental evidences indicated a role of TRPM8 in cold thermal transduction, different life-threatening tumors, and other pathologies, including migraine, urinary tract dysfunction, dry eye disease, and obesity. Hence, the modulation of the TRPM8 channel could be essential in order to understand its implications in these pathologies and for therapeutic intervention. This short review will cover recent progress on the TRPM8 agonists and antagonists, describing newly reported chemotypes, and their application in the pharmacological characterization of TRPM8 in health and disease. The recently described structures of the TRPM8 channel alone or complexed with known agonists and PIP2 are also discussed.

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“…A number of thermosensitive TRP channels were discovered in the sensory vagus nerve, including TRPV1-4, TRPM8, and TRPA1 using a variety of techniques. First, isolated vagal sensory neurons that responded to temperature stimuli as revealed by calcium imaging also responded to TRP channel specific agonists [29,101,112,118]. For example, in one study, most neurons (80%) that were activated by cooling also responded to icilin, a TRPM8 specific agonist while 90% neurons that responded to moderate heating also responded to capsaicin, a TRPV1 specific agonist [118].…”

Section: Vagal Afferents and Visceral Thermal Sensationmentioning

confidence: 99%

Body thermal responses and the vagus nerve

Chang

2019

Neuroscience Letters

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While thermosensation from external environment has been extensively studied, physiological responses to temperature changes inside the body and the underlying regulatory mechanisms are less understood. As a critical link between body and brain that relays visceral organ information and regulates numerous physiological functions, the vagus nerve has been proposed to mediate diverse visceral thermal reflexes and indirectly regulate body temperature. However, the precise role of the vagus nerve in body thermal responses or visceral organ-related thermoregulation is still under debate due to extensive contradictory results. This data discrepancy is likely due to the high cell heterogeneity in the vagus nerve, as diverse vagal neuron types mediate numerous and sometimes opposite physiological functions. Here, we will review evidences that support and against the role of the vagus nerve in body thermosensation and thermoregulation and discuss potential future approaches for better understanding of this critical issue.

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Vagus nerve is involved in the changes in body temperature induced by intragastric administration of 1,8-cineole via TRPM8 in mice

Cited by 10 publications

References 24 publications

TRPM8: A Therapeutic Target for Neuroinflammatory Symptoms Induced by Severe Dry Eye Disease

TRPM8: A Therapeutic Target for Neuroinflammatory Symptoms Induced by Severe Dry Eye Disease

Recent Progress in TRPM8 Modulation: An Update

Body thermal responses and the vagus nerve

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