Psychophysical and vasomotor evidence for interdependency of TRPA1 and TRPV1-evoked nociceptive responses in human skin: an experimental study

Nielsen, Thomas Arendt; Eriksen, Matilde Alida; Gazerani, Parisa; Andersen, Hjalte Holm

doi:10.1097/j.pain.0000000000001298

Cited by 13 publications

(12 citation statements)

References 88 publications

(126 reference statements)

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“…54,55 In the present study, the provided heat stimuli (48°C in experiment 2) were deliberately kept so brief that no sensory sensitization was present in the secondary area. 56 In line with the present findings, Ward et al 57 delivered 48°C heat counterstimuli immediately adjacent to the itch provocation site and observed inhibitory results approximately in between the present effects of homotopic and heterotopic intrasegmental counterstimulation.…”

Section: Discussionsupporting

confidence: 90%

“…Skin, wherein secondary hyperalgesia is present, is known to be resistant to experimentally evoked itch (both histaminergic and nonhistaminergic) . In the present study, the provided heat stimuli (48 °C in experiment 2) were deliberately kept so brief that no sensory sensitization was present in the secondary area . In line with the present findings, Ward et al .…”

Section: Discussionmentioning

confidence: 99%

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Antipruritic effects of transient heat stimulation on histaminergic and nonhistaminergic itch

2019

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Summary Background Chronic itch is notoriously difficult to treat. Counterstimuli are able to inhibit itch, but this principle is difficult to apply in clinical practice, and the mechanisms behind counterstimulation‐induced itch suppression in humans are unclear. Objectives Firstly, to analyse the stimulus–response effects of transient heat stimuli on histaminergic and nonhistaminergic itch, and secondly, to investigate whether the antipruritic effect depends on homotopic (peripheral mediation) or heterotopic (central mediation) counterstimulation relative to the itch provocation site. Methods Eighteen healthy volunteers participated (eight female, mean age 25·7 ± 0·8 years). Itch was evoked on premarked areas of the volar forearms, by either histamine (1% solution) or cowhage (35–40 spicules). In addition to the itch provocations (experiment 1), 5‐s homotopic heat stimuli at 32, 40, 45 or 50 °C were applied. In experiment 2, heat stimuli were applied either homotopically, intrasegmentally (next to the provocation site) or extrasegmentally (dorsal forearm). Itch intensity was evaluated throughout the procedures using a digital visual analogue scale. Results Homotopic counterstimuli inhibited histaminergic itch by 41·3% at 45 °C (P < 0·01) and by 76·7% at 50 °C (P < 0·001). Cowhage‐induced itch was less prone to counterstimulation and was significantly diminished only at 50 °C, by 43·6% (P = 0·009). Counterstimulations applied heterotopically were not able to inhibit itch significantly. Conclusions Itch pathway‐specific effects of counterstimuli were observed between homo‐ and heterotopic stimulation. Histaminergic itch was robustly inhibited by short‐term homotopic noxious heat stimuli for up to 10 min. Nonhistaminergic itch was only weakly inhibited. The inhibitory effects exerted by the short‐term heat stimuli only occurred following homotopic counterstimulation.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Antipruritic effects of transient heat stimulation on histaminergic and nonhistaminergic itch

2019

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“…In our previous study, by direct recordings of spikes from dural nerves, we found that the firing was preferentially mediated by activation of TRPV1 receptors (Koroleva et al, 2017 ). Notably, TRPV1 and TRPA1, two members of the TRP receptors family are often co-localized (Nielsen et al, 2018 ). Moreover, there are data that these channels can be heteromerized (Fischer et al, 2014 ; Weng et al, 2015 ) suggesting that H 2 S might act in employing these channels complex.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Hydrogen Sulfide Against the ATP-Induced Meningeal Nociception

Koroleva

Ermakova

Mustafina

et al. 2020

Front. Cell. Neurosci.

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We previously showed that extracellular ATP and hydrogen sulfide (H 2 S), a recently discovered gasotransmitter, are both triggering the nociceptive firing in trigeminal nociceptors implicated in migraine pain. ATP contributes to meningeal nociception by activating the P2X3 subunit-containing receptors whereas H 2 S operates mainly via TRP receptors. However, H 2 S was also proposed as a neuroprotective and anti-nociceptive agent. This study aimed to test the effect of H 2 S on ATP-mediated nociceptive responses in rat meningeal afferents and trigeminal neurons and on ATP-induced degranulation of dural mast cells. Electrophysiological recording of trigeminal nerve activity in meninges was supplemented by patch-clamp and calcium imaging studies of isolated trigeminal neurons. The H 2 S donor NaHS induced a mild activation of afferents and fully suppressed the subsequent ATP-induced firing of meningeal trigeminal nerve fibers. This anti-nociceptive effect of H 2 S was specific as an even stronger effect of capsaicin did not abolish the action of ATP. In isolated trigeminal neurons, NaHS decreased the inward currents and calcium transients evoked by activation of ATP-gated P2X3 receptors. Moreover, NaHS prevented ATP-induced P2X7 receptor-mediated degranulation of meningeal mast cells which emerged as triggers of migraine pain. Finally, NaHS decreased the concentration of extracellular ATP in the meningeal preparation. Thus, H 2 S exerted the multiple protective actions against the nociceptive effects of ATP. These data highlight the novel pathways to reduce purinergic mechanisms of migraine with pharmacological donors or by stimulation production of endogenous H 2 S.

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“…Another recent work suggests that TRPA1 nociceptive responses in human skin strongly depend on intact capsaicin-sensitive, TRPV1 + fibers [21]. In their work, Nielsen and colleagues investigated whether functional responses from the subpopulation of TRPA1 + nociceptors could be evoked after defunctionalization of TRPV1 + nociceptors by cutaneous application of high-concentration capsaicin.…”

Section: Some Of the Most Recent Findings Regarding The Role Of Trmentioning

confidence: 99%

“…In their work, Nielsen and colleagues investigated whether functional responses from the subpopulation of TRPA1 + nociceptors could be evoked after defunctionalization of TRPV1 + nociceptors by cutaneous application of high-concentration capsaicin. It has been found that ablation of cutaneous capsaicin-sensitive afferents caused consistent and equal inhibition of both TRPV1- and TRPA1-provoked responses assessed psychophysically and by imaging of vasomotor responses [21].…”

Section: Some Of the Most Recent Findings Regarding The Role Of Trmentioning

confidence: 99%

Multifunctional TRPV1 Ion Channels in Physiology and Pathology with Focus on the Brain, Vasculature, and Some Visceral Systems

Storozhuk

Moroz

Zholos

2019

BioMed Research International

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TRPV1 has been originally cloned as the heat and capsaicin receptor implicated in acute pain signalling, while further research has shifted the focus to its importance in chronic pain caused by inflammation and associated with this TRPV1 sensitization. However, accumulating evidence suggests that, apart from pain signalling, TRPV1 subserves many other unrelated to nociception functions in the nervous system. In the brain, TRPV1 can modulate synaptic transmission via both pre- and postsynaptic mechanisms and there is a functional crosstalk between GABA receptors and TRPV1. Other fundamental processes include TRPV1 role in plasticity, microglia-to-neuron communication, and brain development. Moreover, TRPV1 is widely expressed in the peripheral tissues, including the vasculature, gastrointestinal tract, urinary bladder, epithelial cells, and the cells of the immune system. TRPV1 can be activated by a large array of physical (heat, mechanical stimuli) and chemical factors (e.g., protons, capsaicin, resiniferatoxin, and endogenous ligands, such as endovanilloids). This causes two general cell effects, membrane depolarization and calcium influx, thus triggering depending on the cell-type diverse functional responses ranging from neuronal excitation to secretion and smooth muscle contraction. Here, we review recent research on the diverse TRPV1 functions with focus on the brain, vasculature, and some visceral systems as the basis of our better understanding of TRPV1 role in different human disorders.

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Psychophysical and vasomotor evidence for interdependency of TRPA1 and TRPV1-evoked nociceptive responses in human skin: an experimental study

Cited by 13 publications

References 88 publications

Antipruritic effects of transient heat stimulation on histaminergic and nonhistaminergic itch

Antipruritic effects of transient heat stimulation on histaminergic and nonhistaminergic itch

Protective Effects of Hydrogen Sulfide Against the ATP-Induced Meningeal Nociception

Multifunctional TRPV1 Ion Channels in Physiology and Pathology with Focus on the Brain, Vasculature, and Some Visceral Systems

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