Effects of Current Density on Nociceptor Activation Upon Electrical Stimulation in Humans

Landmann, Gunther; Stockinger, Lenka; Lustenberger, Corinne; Schmelz, Martin; Rukwied, Roman

doi:10.1111/papr.12339

Cited by 10 publications

(9 citation statements)

References 47 publications

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“…Electrically induced pain thresholds recorded from both forearms prior to the patch application were used to calculate the current intensity required for supra‐threshold electrical stimulation (1.5‐fold pain threshold) as this initial level was kept constant throughout the entire experimental period. As described previously (Landmann et al., ), electrical stimulation pulses of 1.5‐fold pain threshold were delivered in five consecutive blocks at 15 s intervals. Each block consisted of 10 monophasic rectangular pulses of 5–10–20–50–100 Hz frequencies, respectively, and frequency‐blocks were applied in randomized order.…”

Section: Methodsmentioning

confidence: 99%

Short lasting transient effects of a capsaicin 8% patch on nociceptor activation in humans

Landmann

Lustenberger

Schleinzer

et al. 2016

European Journal of Pain

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Axonal nociceptor function assessed by electrical excitability tests supplements threshold tests of nociceptive endings. The differential analgesic effects of 8% capsaicin patches may be attributed to the kinetics of capsaicin and the different depth of nociceptive nerve fibres, yet, the time course does not match the long-lasting analgesia observed in neuropathic pain patients treated with the same patch. WHAT DOES THIS STUDY ADD?: Axonal nociceptor function assessed by supra-threshold electrical excitability tests did not coincide with capsaicin-induced transduction changes supplementing threshold measures of terminal nociceptor endings. Threshold measurements do not reflect the sustained effect of pain relief seen in neuropathic pain patients. Capsaicin-sensitive nociceptors responsible for spontaneous pain are either not specifically tested with currently available sensory stimulation protocols or have higher capsaicin sensitivity or slower recovery under neuropathic conditions.

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Section: Methodsmentioning

confidence: 99%

Short lasting transient effects of a capsaicin 8% patch on nociceptor activation in humans

Landmann

Lustenberger

Schleinzer

et al. 2016

European Journal of Pain

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“…Intradermal injection of NGF is known to facilitate action potential generation and conduction (Obreja, et al., 2011; Obreja et al., 2018; Rukwied et al., 2014). In order to induce action potential discharge preferentially in nociceptors we designed an electrode (Landmann et al., 2016) and a stimulus profile (Rukwied et al., 2020) to specifically depolarize mechano‐sensitive C‐nociceptors. A half sine wave constant current stimulus provokes a burst of action potentials (Rukwied et al., 2020) and we found that NGF increased the pain ratings to the most intense amplitude of half sine wave stimulation.…”

Section: Discussionmentioning

confidence: 99%

Nerve growth factor sensitizes nociceptors to C‐fibre selective supra‐threshold electrical stimuli in human skin

Schnakenberg

Thomas

Schmelz

et al. 2020

European Journal of Pain

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BackgroundIntradermal injection of 1 µg nerve growth factor (NGF) causes sustained nociceptor sensitization. Slowly depolarizing electrical current preferentially activates C‐nociceptors.MethodsWe explored the differential contribution of A‐delta and C‐nociceptors in NGF‐sensitized skin using slowly depolarizing transcutaneous electrical current stimuli, CO2 laser heat, mechanical impact, and A‐fibre compression block. In 14 healthy volunteers, pain rating was recorded on a numeric scale at days 1–14 after NGF treatment. Ratings during A‐fibre conduction block were investigated at days 3 and 7 post‐NGF.ResultsPain ratings to electrical, CO2 heat and mechanical impact stimuli were enhanced (>30%, p < .0005, ANOVA) at NGF‐injection sites. Axon reflex erythema evoked by electrical stimulation was also larger at NGF‐injection sites (p < .02, ANOVA). Diminution of pain during continuous (1 min) sinusoidal current stimulation at 4 Hz was less pronounced after NGF (p < .05, ANOVA). Pain ratings to electrical sinusoidal and mechanical impact stimuli during A‐fibre conduction block were significantly elevated at the NGF sites compared to NaCl‐treated skin (p < .05, ANOVA).ConclusionsNGF‐induced sensitization of human skin to electrical and mechanical stimuli is primarily driven by C‐nociceptors with little contribution from A‐delta fibres. Less‐pronounced accommodation during ongoing sinusoidal stimulation suggests that NGF could facilitate axonal spike generation and conduction in primary afferent nociceptors in humans. Further studies using this sinusoidal electrical stimulation profile to investigate patients with chronic inflammatory pain may allow localized assessment of skin C‐nociceptors and their putative excitability changes under pathologic conditions.SignificanceThe application of novel slowly depolarizing electrical stimuli demonstrated a predominant C‐nociceptor sensitization in NGF‐treated skin. Increased pain ratings, larger axon reflex erythema and less accommodation of C‐fibres to ongoing sinusoidal stimulation all indicated an enhanced nociceptor discharge after NGF. A‐fibre conduction block had little effect on electrical and mechanical hyperalgesia skin in NGF‐treated compared to NaCl‐treated skin. This electrical stimulus profile may be applicable for patients with chronic inflammatory pain, allowing localized assessment of skin C‐nociceptors and their putative excitability changes under pathologic conditions.

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“…Note that with a rectangular stimulation paradigm of 0.25 Hz and 0.5 ms pulse duration the transcutaneous electrical thresholds were >9 mA for C-nociceptor stimulation (electrode covering 30 mm 2 ) (30). If higher current densities are provided at the stimulation sites by using pointed (1 mm diameter) or bipolar (2 mm length, 3 mm distance) pin electrodes (stimulation frequency 1-10 Hz) current intensities exceeding 5 mA are required for C-fiber activation (31,32). Given the low intensities and high frequencies used in the protocols summarized, most likely myelinated A-fibers had been stimulated.…”

Section: Electrically Evoked Itch In Healthy Human Subjectsmentioning

confidence: 99%

Electrically Evoked Itch in Human Subjects

Solinski

Rukwied

2021

Front. Med.

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Administration of chemicals (pruritogens) into the skin evokes itch based on signal transduction mechanisms that generate action potentials mainly in mechanically sensitive and insensitive primary afferent C-fibers (pruriceptors). These signals from peripheral neurons are processed in spinal and supra-spinal centers of the central nervous system and finally generate the sensation of itch. Compared to chemical stimulation, electrical activation of pruriceptors would allow for better temporal control and thereby a more direct functional assessment of their activation. Here, we review the electrical stimulation paradigms which were used to evoke itch in humans in the past. We further evaluate recent attempts to explore electrically induced itch in atopic dermatitis patients. Possible mechanisms underlying successful pruritus generation in chronic itch patients by transdermal slowly depolarizing electrical stimulation are discussed.

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Effects of Current Density on Nociceptor Activation Upon Electrical Stimulation in Humans

Abstract: Electrical stimulation at high current density using pin electrodes is a sensitive method for investigating "silent" nociceptors, which might therefore preferably be applied in neuropathic pain conditions.

Cited by 10 publications

References 47 publications

Short lasting transient effects of a capsaicin 8% patch on nociceptor activation in humans

Short lasting transient effects of a capsaicin 8% patch on nociceptor activation in humans

Nerve growth factor sensitizes nociceptors to C‐fibre selective supra‐threshold electrical stimuli in human skin

Electrically Evoked Itch in Human Subjects

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