Low but not high rate noxious radiant skin heating evokes a capsaicin-sensitive increase in spinal cord dorsal horn release of substance P

Zachariou, Venetia; Goldstein, Barry D.; Yeomans, David C.

doi:10.1016/s0006-8993(96)01466-7

Cited by 39 publications

(20 citation statements)

References 41 publications

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“…Therefore, ramping thermal stimulation elicits first pain with possible suppression of subsequent second pain in a temporal summation paradigm. In contrast, slow passive distribution of heat to deep layers of the skin following IC stimulation is an effective natural stimulus for unmyelinated, but not for myelinated nociceptors[41; 47]. Substantial summation of late sensations can progress from warmth to VAS ratings of 80 over a series of 20 stimuli[41], when first pain appears late or not at all in series of IC stimuli.…”

Section: Discussionmentioning

confidence: 99%

Methodological Considerations for the Temporal Summation of Second Pain

Eckert

Vierck

Simon

et al. 2017

The Journal of Pain

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Temporal summation of second pain (TSSP) is a psychophysical indication of a central pain encoding mechanism, potentially enhanced in pathological pain conditions. Low frequency repetitive stimulation of unmyelinated (C) nociceptors results in a progressive increase of pain intensity when thermal stimulation intensity remains constant. However, when using different methods of nociceptive delivery to the skin, both regularity and rate of pain enhancement with repetition varies between experiments. Specifically, repetitive ramping up and down from a neutral to a painful temperature has produced weak and inconsistent pain summation. In contrast, repetitive contact of the skin with a preheated probe has generated substantial pain summation. In the present study, TSSP by the intermittent contact (IC) with a preheated thermode and constant contact, ramp and hold (CC) methods were compared during 10 iterations of stimulation of glabrous skin of the hand or hairy forearm skin, with an onset to onset interval of 3.3 sec and stimulus interval of 0.8 sec. Significantly greater TSSP was observed for IC stimulation at both sites (p < .001). Differential activation of myelinated and unmyelinated nociceptors by ramping and tapping may account for different rates of temporal summation of heat pain. Perspective This article presents direct evidence suggesting the constant contact, ramp and hold stimulus may underestimate the level of Temporal Summation of Second Pain. This evidence suggests the re-evaluation of stimulation techniques utilized for Temporal Summation tests, especially within clinical models.

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Section: Discussionmentioning

confidence: 99%

Methodological Considerations for the Temporal Summation of Second Pain

Eckert

Vierck

Simon

et al. 2017

The Journal of Pain

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“…It has been shown in previous studies that light urethane anesthesia (800–1000 mg/kg ip ) does not alter withdrawal latencies to noxious thermal stimuli administered to paws (Yeomans DC et al 1996; Zachariou V et al 1997) or areas innervated by the trigeminal nerve (Tzabazis A et al 2004). The experimenter performing the behavioral tests was blinded to the rat treatment group assignment.…”

Section: Methodsmentioning

confidence: 95%

Trigeminal antihyperalgesic effect of intranasal carbon dioxide

et al. 2010

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Aims-Clinical studies demonstrate attenuation of trigeminal-related pain states such as migraine by intranasal CO 2 application. This study investigated the underlying mechanisms of this observation and its potential use to reverse trigeminal pain and hypersensitivity.Main methods-We used a behavioral rat model of capsaicin-induced trigeminal thermal hyperalgesia, intranasal CO2 application and several pharmacologic agents such as carbonic anhydrase, acid-sensing ion channels (ASICs), and TRPV1 blocker as well as acidic buffer solutions to investigate and mimick the underlying mechanism.Key findings-Intranasal CO 2 application produced a robust dose-dependent antihyperalgesic effect in rats that lasted at least one hour. Blockade of nasal carbonic anhydrase with a dorzolamide solution (Trusopt® ophthalmic solution) showed only a non-significant decrease of the antihyperalgesic effect of intranasal CO 2 application. Pharmacologic blockade of ASICs or TRPV 1 receptor significantly attenuated the antihyperalgesic effect of CO 2 application. The effect of intranasal CO 2 application could be mimicked by application of pH4, but not pH 5, buffer solution to the nasal mucosa. As with CO 2 application, the antihyperalgesic effect of intranasal pH4 buffer was blocked by nasal application of antagonists to ASICs and TRPV 1 receptors.Significance-Our results indicate that intranasal CO 2 application results in a subsequent attenuation of trigeminal nociception, mediated by protonic activation of TRPV 1 and ASIC channels. A potential central mechanism for this attenuation is discussed. The antihyperalgesic effects of intranasal CO 2 application might be useful for the treatment of trigeminal pain states.

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“…For example, slow heat ramps primarily activate C primary afferents, whereas fast heat ramps activate A-delta primary afferents [38,39,41-43,61-63]. Utilizing this method, it has been demonstrated that systemic and spinal administration of morphine or a mu-opioid receptor agonist preferentially attenuates behavioral withdrawal responses to slow heat when compared to those elicited by fast heat applied to the hind paw [38,61].…”

Section: Introductionmentioning

confidence: 99%

Differential effects of the cannabinoid receptor agonist, WIN 55,212-2, on lamina I and lamina V spinal trigeminal nucleus caudalis neurons

Ogawa

Meng

2009

Pain

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Direct application of cannabinoids to the medullary dorsal horn (MDH) inhibits lamina V nociceptive neurons. The present study compared the effect of the cannabinoid receptor agonist, WIN 55,212-2 (WIN-2) on the activity of lamina I and lamina V MDH neurons using extracellular single unit recording in anesthetized rats. Activity evoked by a contact thermode was measured before and after local application of WIN-2 (0.5-2.0 μg/μl) to the brainstem. Fast and slow heat ramps were used to differentiate between activity evoked primarily by A-delta and C primary afferent fibers, respectively. In lamina V neurons, WIN-2 produced a concentration dependent decrease in activity evoked by both fast and slow heat, reaching significance at 1.0 μg/μl. In lamina I neurons, WIN-2 administration inhibited slow heat evoked activity beginning at 1.0 μg/μl but had no significant effect on fast heat evoked activity, even at the highest concentration (2.0 μg/μl). In separate experiments, the effect of intrathecal administration of WIN-2 to the MDH on head withdrawal latencies elicited by fast and slow heat ramps applied to the whisker pad was assessed in lightly anesthetized rats. Head withdrawal latencies elicited by slow but not fast heat stimulation were increased by WIN-2. Taken together, these results emphasize the importance of lamina I neurons in the control of a nociceptive heat-evoked reflex.

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Low but not high rate noxious radiant skin heating evokes a capsaicin-sensitive increase in spinal cord dorsal horn release of substance P

Cited by 39 publications

References 41 publications

Methodological Considerations for the Temporal Summation of Second Pain

Methodological Considerations for the Temporal Summation of Second Pain

Trigeminal antihyperalgesic effect of intranasal carbon dioxide

Differential effects of the cannabinoid receptor agonist, WIN 55,212-2, on lamina I and lamina V spinal trigeminal nucleus caudalis neurons

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