Low intensity intra-epidermal electrical stimulation can activate Aδ-nociceptors selectively

Abstract

In the past 30years, 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 Abeta-, Adelta- 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 Adelta-fibres, but not of Abeta-fibres. Taken together, our results provide converging evidence that Adelta-nociceptors can be activated selectively using IES, provided that low intensities of stimulation are used.

Unmasking the obligatory components of nociceptive event-related brain potentials

“…Similar to what has been described in previous studies (Inui et al 2003a;Mouraux et al 2010), the A␦-SEP elicited by nociceptive stimuli presented with a long and variable ISI consisted of a large negative-positive potential, labeled N2-P2, which was maximal at the scalp vertex, and whose shape and scalp topography resembled closely the shape and scalp topography of the N2-P2 complex of laser-evoked potentials. The amplitude of the N2-P2 elicited by IES applied with a variable 5-to 10-s ISI was more than one order of magnitude greater than the amplitude of the P1 wave elicited by IES applied with a constant 1-s ISI.…”

“…Importantly, the scalp topography and latency of the ERPs elicited by a single pulse of IES were highly similar to the scalp topography and latency of the ERPs elicited by a train of three pulses, indicating that both types of IES activated the same classes of afferents, i.e., nociceptive A␦ fibers as previously demonstrated in Mouraux et al (2010). Fig.…”

“…However, if the intensity of stimulation is increased, the selectivity of IES is compromised because the stronger currents may also activate more deeply located A␤ fiber afferents. For this reason, Mouraux et al (2010) found that IES delivered at twice the absolute detection threshold (0.08 Ϯ 0.05 mA threshold averaged across the different experiments) only activates nociceptive afferents, whereas IES delivered at 2.5 mA also activates A␤ fibers. Similarly, de Tommaso et al (2011) andPerchet et al (2012) found that IES delivered above the threshold to elicit a sensation qualified as painful (e.g., 1.6 Ϯ 0.5 mA; de Tommaso et al 2011)-i.e., almost 10 times the absolute detection threshold-is not selective for nociceptors, as it elicits brain responses related to the activation of A␤ fibers.…”

“…For this reason, it has been postulated that increasing the number of pulses does not affect the selectivity of IES for nociceptive afferents, although repetition of the electrical pulse is likely to activate some additional fibers brought to a subthreshold potential by the preceding pulses. Therefore, in the present study, both TES and IES were delivered either as a single constantcurrent square-wave pulse lasting 0.5 ms (as in Mouraux et al 2010) or as a train of three consecutive 0.5-ms pulses separated by a 5-ms interpulse interval (Fig. 1).…”

Parallel Processing of Nociceptive and Non-nociceptive Somatosensory Information in the Human Primary and Secondary Somatosensory Cortices: Evidence from Dynamic Causal Modeling of Functional Magnetic Resonance Imaging Data

“…For each participant, stimulus intensity (6 Ϯ 2 mA) was adjusted to elicit a nonpainful paresthesia in the sensory territory of the nerve. The intensity of electrical stimulation was above the electrical activation threshold of A␤ fibers (which convey innocuous non-nociceptive sensations) but well below the electrical activation threshold of nociceptive A␦ and C fibers (Burgess and Perl, 1967;Mouraux et al, 2010), and never elicited a painful percept. Visual stimuli consisted of a bright white disk (ϳ9°v iewing angle) displayed on the projection screen, above the right foot, for 100 ms. Auditory stimuli were loud (65 dB), right-lateralized 800 Hz tones (0.5 left/right amplitude ratio; 50 ms duration; 5 ms rise and fall times), delivered binaurally through custom-built pneumatic earphones bored into a set of low-profile ear defenders (Mayhew et al, 2010).…”