Low intensity intra-epidermal electrical stimulation can activate A [delta]-nociceptors selectively (original) (raw)
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Low intensity intra-epidermal electrical stimulation can activate Aδ-nociceptors selectively
Pain, 2010
In the past 30 years, the study of nociception has relied mostly on thermal stimulation to activate nociceptors selectively. However, thermal stimulation suffers from some important limitations. For this reason, investigators have proposed intra-epidermal electrical stimulation (IES) as an alternative method to activate nociceptors selectively. This method relies on the fact that nociceptors are located mainly in the epidermis, while non-nociceptive fibres terminate more deeply in the dermis. Therefore, provided that the difference in receptor depth is sufficient, electric currents spatially restricted to the epidermal layers might activate nociceptors selectively. Here, we examined whether or not IES provides a fully selective nociceptive input. In a first experiment, we used capsaicin to induce a selective denervation of capsaicin-sensitive nociceptors, and thereby test whether the responses to IES are mediated by this population of afferent fibres. We found that capsaicin abolishes both the behavioural and the electrophysiological responses to IES applied at twice the perceptual threshold. In a second experiment, we applied a nerve pressure block to the superficial radial nerve to induce a temporally dissociated impairment of Ab-, Ad-and C-fibre afferents, and thereby determine the fibre populations contributing to the responses elicited by IES. We found that the time course of the blockade of the responses to IES follows closely the time course of the blockade of Ad-fibres, but not of Ab-fibres. Taken together, our results provide converging evidence that Ad-nociceptors can be activated selectively using IES, provided that low intensities of stimulation are used.
Neuroscience Letters, 2014
Currently, the study of nociception in humans relies mainly on thermal stimulation of heatsensitive nociceptive afferents. To circumvent some limitations of thermal stimulation, it was proposed that intra-epidermal electrical stimulation (IES) could be used as an alternative method to activate nociceptors selectively. The selectivity of IES relies on the fact that it can generate a very focal electrical current and, thereby, activate nociceptive free nerve endings located in the epidermis without concomitantly activating non-nociceptive mechanoreceptors located more deeply in the dermis. However, an important limitation of IES is that it is selective for nociceptors only when very low current intensities are used. At these intensities, the stimulus generates a very weak percept, and the signal-to-noise ratio of the elicited evoked potentials (EPs) is very low. To circumvent this limitation, it was proposed that the strength of the nociceptive afferent volley could be increased through temporal summation, using short trains of repeated IES. Here, we characterized the intensity of perception and EPs elicited by trains of 2, 3 and 4 IES delivered using a 5-ms inter-stimulus interval. We found that both the intensity of perception and the magnitude of EPs significantly increased with the number of pulses. In contrast, the latency of the elicited EPs was not affected by the number of pulses, indicating that temporal summation did not affect the type of activated fibers and, therefore, that trains of IES can be used to increase the reliability of stimulus-evoked responses while still preserving its selectivity for nociceptors.
2021
A sustained sensory stimulus with a periodic variation of intensity creates an electrophysiological brain response at associated frequencies, referred to as the steady-state evoked potential (SSEP). The SSEPs elicited by the periodic stimulation of nociceptors in the skin may represent activity of a brain network that is primarily involved in nociceptive processing. Exploring the behavior of this network could lead to valuable insights regarding the pathway from nociceptive stimulus to pain perception. We present a method to directly modulate the pulse rate of nociceptive afferents in the skin with a multisine waveform through intra-epidermal electric stimulation. The technique was demonstrated in healthy volunteers. Each subject was stimulated using a pulse sequence modulated by a multisine waveform of 3, 7 and 13 Hz. The EEG was analyzed for the presence of the base frequencies and associated (sub)harmonics. Topographies showed significant central and contralateral SSEP responses ...
The Journal of …, 2011
The periodic presentation of a sensory stimulus induces, at certain frequencies of stimulation, a sustained electroencephalographic response known as steady-state evoked potential (SS-EP). In the somatosensory, visual, and auditory modalities, SS-EPs are considered to constitute an electrophysiological correlate of cortical sensory networks resonating at the frequency of stimulation. In the present study, we describe and characterize, for the first time, SS-EPs elicited by the selective activation of skin nociceptors in humans. The stimulation consisted of 2.3-s-long trains of 16 identical infrared laser pulses (frequency, 7 Hz), applied to the dorsum of the left and right hand and foot. Two different stimulation energies were used. The low energy activated only C-nociceptors, whereas the high energy activated both Aδ- and C-nociceptors. Innocuous electrical stimulation of large-diameter Aβ-fibers involved in the perception of touch and vibration was used as control. The high-energy nociceptive stimulus elicited a consistent SS-EP, related to the activation of Aδ-nociceptors. Regardless of stimulus location, the scalp topography of this response was maximal at the vertex. This was noticeably different from the scalp topography of the SS-EPs elicited by innocuous vibrotactile stimulation, which displayed a clear maximum over the parietal region contralateral to the stimulated side. Therefore, we hypothesize that the SS-EPs elicited by the rapid periodic thermal activation of nociceptors may reflect the activation of a network that is preferentially involved in processing nociceptive input and may thus provide some important insight into the cortical processes generating painful percepts.
Area 3a Neuron Response to Skin Nociceptor Afferent Drive
Cerebral Cortex, 2008
Area 3a neurons are identified that respond weakly or not at all to skin contact with a 25-38°C probe, but vigorously to skin contact with the probe at > >49°C. Maximal rate of spike firing associated with 1-to 7-s contact at > >49°C occurs 1-2 s after probe removal from the skin. The activity evoked by 5-s contact with the probe at 51°C remains above-background for~20 s after probe retraction. After 1-s contact at 55-56°C activity remains above-background for~4 s. Magnitude of spike firing associated with 5-s contact increases linearly as probe temperature is increased from 49-51°C. Intradermal capsaicin injection elicits a larger (~2.53) and longerlasting (1003) increase in area 3a neuron firing rate than 5-s contact at 51°C. Area 3a neurons exhibit enhanced or novel responsivity to 25-38°C contact for a prolonged time after intradermal injection of capsaicin or a, b methylene adenosine triphosphate. Their 1) delayed and persisting increase in spike firing in response to contact at > >49°C, 2) vigorous and prolonged response to intradermal capsaicin, and 3) enhanced and frequently novel response to 25-38°C contact following intradermal algogen injection or noxious skin heating suggest that the area 3a neurons identified in this study contribute to second pain and mechanical hyperalgesia/allodynia.
Brain Topography
Recent studies have established the presence of nociceptive steady-state evoked potentials (SSEPs), generated in response to thermal or intra-epidermal electric stimuli. This study explores cortical sources and generation mechanisms of nociceptive SSEPs in response to intra-epidermal electric stimuli. Our method was to stimulate healthy volunteers (n = 22, all men) with 100 intra-epidermal pulse sequences. Each sequence had a duration of 8.5 s, and consisted of pulses with a pulse rate between 20 and 200 Hz, which was frequency modulated with a multisine waveform of 3, 7 and 13 Hz (n = 10, 1 excluded) or 3 and 7 Hz (n = 12, 1 excluded). As a result, evoked potentials in response to stimulation onset and contralateral SSEPs at 3 and 7 Hz were observed. The SSEPs at 3 and 7 Hz had an average time delay of 137 ms and 143 ms respectively. The evoked potential in response to stimulation onset had a contralateral minimum (N1) at 115 ms and a central maximum (P2) at 300 ms. Sources for the...
Brain, 2000
Burning pain was induced in healthy human subjects by of mechano-responsive C-units was too short to account for the duration of the burning pain. The latter generally intracutaneous injections of capsaicin (20 µl, 0.1%) in the innervation territory of the cutaneous branch of the were desensitized to mechanical stimulation at the injection site, whereas 8 of 17 of the originally mechano-peroneal nerve and the pain responses were compared with the activation patterns of afferent C-fibres recorded insensitive C-units became responsive to mechanical probing at the injection site after capsaicin. Responses by microneurography. Responsiveness of single units to mechanical or heat stimuli or to sympathetic reflex typically started several seconds after the onset of the mechanical stimulus in parallel with pain sensations. We provocation tests was determined by transient slowing of conduction velocity following activation (marking did not observe sensitization to brushing or to punctate stimuli in uninjured parts of the innervation territory. technique). Capsaicin activated each of 12 mechanoresponsive and 17 of 20 mechano-insensitive C-units. Differential capsaicin sensitivity adds to the cumulating evidence for the existence of two categories of functionally However, the duration of the responses to capsaicin was significantly longer in mechano-insensitive C-units different nociceptors in human skin, with a special role for mechano-insensitive fibres in sensitization and (median 170 s; quartiles 80-390) compared with mechanoresponsive C-units (8 s; 4-10). The activation times of hyperalgesia. Possible structural differences between these two categories are discussed, including the role of mechano-insensitive C-units closely matched the duration of capsaicin-induced pain responses, whereas activation tetrodotoxin-resistant sodium channels.
Journal of neuroscience methods, 2017
No satisfactory neurophysiological test for nociceptive afferents is available to date. Laser stimuli present risks of skin damage, whilst electrical stimulation through specially designed electrodes is not selective enough. We present a new electrode designed according to critical issues identified in preliminary computer simulations concerning electric field gradient through the skin. To provide selective stimulation the activating electric field must be limited to intraepidermal free nerve endings. To this end, a new interdigitated electrode (IDE) was made of conductive rails arranged in a comb-like micropattern, situated only 150μm apart from each other (150 IDE) and alternately connected to the opposite poles of the stimulator. Evoked potentials recorded from the scalp were obtained after stimulation with the 150 IDE and with a similarly designed, but more widely spaced electrode (1000μm, or 1000 IDE). Small amplitude early and medium latency components were recorded with the 1...