Pinprick-evoked brain potentials: a novel tool to assess central sensitization of nociceptive pathways in humans

Abstract

Although hyperalgesia to mechanical stimuli is a frequent sign in patients with inflammation or neuropathic pain, there is to date no objective electrophysiological measure for its evaluation in the clinical routine. Here we describe a technique for recording the electroencephalographic (EEG) responses elicited by mechanical stimulation with a flat-tip probe (diameter 0.25 mm, force 128 mN). Such probes activate Aδ nociceptors and are widely used to assess the presence of secondary hyperalgesia, a psychophysical correlate of sensitization in the nociceptive system. The corresponding pinprick-evoked potentials (PEPs) were recorded in 10 subjects during stimulation of the right and left hand dorsum before and after intradermal injection of capsaicin into the right hand and in 1 patient with a selective lesion of the right spinothalamic tract. PEPs in response to stimulation of normal skin were characterized by a vertex negative-positive (NP) complex, with N/P latencies and amplitudes of 111/245 ms and 3.5/11 μV, respectively. All subjects developed a robust capsaicin-induced increase in the pain elicited by pinprick stimulation of the secondary hyperalgesic area (+91.5%, P < 0.005). Such stimulation also resulted in a significant increase of the N-wave amplitude (+92.9%, P < 0.005), but not of the P wave (+6.6%, P = 0.61). In the patient, PEPs during stimulation of the hypoalgesic side were reduced. These results indicate that PEPs 1) reflect cortical activities triggered by somatosensory input transmitted in Aδ primary sensory afferents and spinothalamic projection neurons, 2) allow quantification of experimentally induced secondary mechanical hyperalgesia, and 3) have the potential to become a diagnostic tool to substantiate mechanical hyperalgesia in patients with presumed central sensitization.

What do we really know about newborn infant pain?

“…Electroencephalography, in contrast, is a non-invasive neurophysiological method that records the electrical activity of the brain at the scalp, largely from superficial regions, such as the somatosensory cortex, because voltage changes dissipate from deeper subcortical structures over a certain distance. It is possible to observe event-related changes in the EEG traces following certain stimuli, including noxious laser, pinprick and heel lance (Zhang et al 2012;Fabrizi et al 2013;Iannetti et al 2013). Recently, studies have identified an event-related potential in newborn infants and infants up to 1 year old, which is specific to noxious stimulation (Slater et al 2010b,c;Fabrizi et al 2011;Verriotis et al 2015).…”

Characterizing pinprick-evoked brain potentials before and after experimentally induced secondary hyperalgesia

“…Instead of applying the pinprick stimulus as fast as possible as in the study of Iannetti et al (2013), the pinprick stimulus was applied and removed slowly and maintained against the skin for at least 1 s. The reason for doing this is that the actual force that is applied onto the skin is dependent on the velocity at which the stimulus is delivered. To be sure that the actual delivered force is the same as the planned force, the pinprick stimulus should be applied onto the skin in a slow fashion (www.mrc-systems.de/ englisch/products/pinprick.html).…”

“…It would thus be of great value to have a noninvasive clinical and research laboratory tool that is able to reliably assess sensitization of mechanical nociceptive pathways. One of these tools could be the recording of pinprick event-related brain potentials (ERPs).IRecently, Iannetti et al (2013) recorded for the first time ERPs elicited by mechanical pinprick stimulation before and after intradermal injection of capsaicin in the area of secondary hyperalgesia in healthy volunteers. The mechanical pinprick stimulation was performed by quickly applying and removing a sharp-tipped probe (0.25-mm diameter).…”

“…Recently, Iannetti et al (2013) recorded for the first time ERPs elicited by mechanical pinprick stimulation before and after intradermal injection of capsaicin in the area of secondary hyperalgesia in healthy volunteers. The mechanical pinprick stimulation was performed by quickly applying and removing a sharp-tipped probe (0.25-mm diameter).…”

High-frequency electrical stimulation of the human skin induces heterotopical mechanical hyperalgesia, heat hyperalgesia, and enhanced responses to nonnociceptive vibrotactile input

“…Recently, Iannetti et al (2013) recorded ERPs in response to pinprick stimulation before and after intradermal injection of capsaicin in the adjacent skin. The pinprick stimulation elicited a typical biphasic ERP waveform (N1 and P2 waves) with latencies compatible with the conduction of myelinated A␤-or A␦-fiber afferents.…”