Effects of scratching and other counterstimuli on responses of trigeminothalamic tract neurons to itch-inducing stimuli in rats

Lipshetz, Brett; Giesler, Glenn J.

doi:10.1152/jn.00326.2015

Cited by 12 publications

(10 citation statements)

References 37 publications

(58 reference statements)

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“…Yosipovitch et al (2007) applied alternating thermal stimuli 3 cm distally to a site of histamineinduced itch (i.e., intra-segmentally) and still observed significant antipruritic effects for stimuli intensity in, or close to, the noxious range (Yosipovitch et al 2007). Interestingly, a recent study documented that pruriceptive signaling is only significantly reduced by homotopic scratching and hence other counter-stimulation modalities appear to rely on different mechanisms of itch inhibition (Lipshetz and Giesler 2016). Seemingly contradictory to our results, Murray and Weaver (1975) found a decrease of itch intensity in response to a contralaterally applied modified cold pressor pain stimulus.…”

Section: The Perception Of Itch Is Not Modulated By Conditioning Paincontrasting

confidence: 99%

“…This is in accordance with an earlier study using a similar study design, in which CPM effect was found for pressure pain thresholds and suprathreshold heat stimulation but not for mechanical detection thresholds or warmth detection thresholds (Leffler et al 2002). Interestingly, the inhibition of itch by application of various homotopic or intra-segmentally applied counter-stimuli is well established, while itch inhibition by application of counter-stimuli far away from the area of induced itch is much less studied (Bromma et al 1995;Yosipovitch et al 2005;Pfab et al 2006;Lipshetz and Giesler 2016;van Laarhoven et al 2016). Noxious thermal or mechanical stimuli such as pinching or scratching in or close to an area of induced itch will greatly diminish the magnitude of the experienced itch transiently.…”

Section: The Perception Of Itch Is Not Modulated By Conditioning Painsupporting

confidence: 90%

See 1 more Smart Citation

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

Andersen

Imai

Petersen

et al. 2016

Somatosensory & Motor Research

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This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers.

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Section: The Perception Of Itch Is Not Modulated By Conditioning Paincontrasting

confidence: 99%

Section: The Perception Of Itch Is Not Modulated By Conditioning Painsupporting

confidence: 90%

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

Andersen

Imai

Petersen

et al. 2016

Somatosensory & Motor Research

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“…Most RVM ON cells were excited by pruritogens and scratching the skin, and OFF cells were inhibited by both. Scratching inhibited the pruritogen-evoked responses of spinal neurons (Akiyama et al 2011(Akiyama et al , 2012bDavidson et al 2009;Lipshetz and Giesler 2016;Nishida et al 2013). Scratch inhibition of spinal pruriceptive neurons was partially reduced by spinal transection, implying the involvement of both segmental and supraspinal inhibitory mechanisms (Akiyama et al 2011).…”

Section: Scratching and Descending Pathwaysmentioning

confidence: 99%

Effects of pruritogens and algogens on rostral ventromedial medullary ON and OFF cells

Follansbee

Akiyama

Fujii

et al. 2018

Journal of Neurophysiology

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RVM ON- and OFF cells are thought to facilitate and inhibit spinal nociceptive transmission, respectively. However, it is unknown how ON and OFF cells respond to pruritic stimuli or how they contribute to descending modulation of spinal itch signaling. In pentobarbital-anesthetized mice, single-unit recordings were made in RVM from ON and OFF cells identified by their respective increase or decrease in firing that occurred just prior to nocifensive hindlimb withdrawal elicited by paw pinch. Of RVM ON cells, 75% (21/28) were excited by intradermal (id) histamine, 50% (10/20) by id chloroquine, and 75% (27/36) by id capsaicin. Most chemically-responsive units also responded to a scratch stimulus applied to the injected hindpaw. Few ON cells responded to id injection of vehicle (saline: 5/32; Tween 2/17), but still responded to scratching. For OFF cells, id histamine and scratching inhibited 32% (6/19) with no effect of histamine in the remainder. Id chloroquine inhibited 44% (4/9) and id capsaicin inhibited 61% (11/18) of OFF cells. Few OFF cells were affected by vehicles (Tween: 1 inhibited, 7 unaffected; saline: 3 excited, 1 inhibited, 8 unaffected). Both ON and OFF cells that responded to one chemical usually also responded to others, while units unresponsive to the first-tested chemical tended not to respond to others. These results indicate that ascending pruriceptive signals activate RVM ON cells and inhibit RVM OFF cells. These effects are considered to facilitate and disinhibit spinal pain transmission, respectively. It is currently not clear if spinal itch transmission is similarly modulated.

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“…Interestingly, in a recent preclinical study, central neuronal firing levels evoked by intradermal pruritogen injection (serotonin) were not reduced by transient noxious heat stimuli (45°C and 50°C for 5 s). 58 However, another study showed that neuronal activation (following dry skin induction) in the superficial dorsal horn was reduced by a longer noxious heat stimulus (48-56°C for 20 s). 59 These findings could suggest that with transient counterstimuli, the upper level of itch transduction remains unchanged, but the inhibitory effect observed in this study relied on peripheral mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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Effects of scratching and other counterstimuli on responses of trigeminothalamic tract neurons to itch-inducing stimuli in rats

Abstract: Lipshetz B, Giesler GJ Jr. Effects of scratching and other counterstimuli on responses of trigeminothalamic tract neurons to itchinducing stimuli in rats.

Cited by 12 publications

References 37 publications

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

Effects of pruritogens and algogens on rostral ventromedial medullary ON and OFF cells

Antipruritic effects of transient heat stimulation on histaminergic and nonhistaminergic itch

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