Brain potentials evoked by intraepidermal electrical stimuli reflect the central sensitization of nociceptive pathways.
Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS.
School of Medical Imaging, Tianjin Medical University, Tianjin, China; Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom; and liangmeng@tmu.edu.cn.
M
M
Liang
Division of Anaesthesia, University of Cambridge, Cambridge, United Kingdom.
M C
MC
Lee
Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom; and.
J
J
O'Neill
Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom; and.
A H
AH
Dickenson
Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom; and.
G D
GD
Iannetti
D000328:Adult; D000344:Afferent Pathways / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002211:Capsaicin / Q000633:toxicity; D059333:Central Nervous System Sensitization / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods*; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory / Q000502:physiology*; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement; D012372:ROC Curve; D011930:Reaction Time / Q000502:physiology; D059629:Signal-To-Noise Ratio; D012867:Skin / Q000294:innervation*; D055815:Young Adult
D002211:Capsaicin
EEG; central sensitization; intraepidermal electrical stimulation; mechanical punctate stimulation; secondary hyperalgesia