Brain responses to transient nociceptive stimuli in humans : EEG and fMRI
Pain may be defined as a primarily subjective and aversive perception inciting the individual to respond to a stimulus constituting a real or potential menace to his integrity. The perception of pain is thus a vital function involving multidimensional sensory, motivational, and cognitive components.
The transduction of nociceptive stimuli occurs at the free nerve endings of nociceptors.
Within the skin, nociceptive free nerve endings terminate within the epidermis and superficial dermal layers.
The nociceptive system, which produces pain, can be viewed as a dual afferent sensory network whose inputs are respectively conveyed by Aδ- and C-nociceptors. Aδ- and C-nociceptors have very different response characteristics and pharmacological properties.
The psychophysical properties of the sensations they mediate (often referred to as ‘first’ and ‘second’ pain) differ greatly. An important fact is that Aδ- and C-fibres have very different conduction velocities. Therefore, several hundreds of milliseconds may often separate the arrival of Aδ- and C-nociceptive inputs at their cortical projections.
A number of human electrophysiological studies, using event-related brain potentials (ERPs), as well as a number of functional brain imaging studies, using either magnetic resonance imaging (MRI) or positron-emitting tomography (PET), have shown that a nociceptive stimulus elicits activity within a widespread cortical network, consistently and bilaterally involving secondary somatosensory, insular, and anterior cingulate cortices. However, the respective contribution of Aδ- and C-nociceptive inputs to these identified brain responses, and how these different nociceptive inputs interact and integrate into a unified painful perception, remains largely unknown.
A number of studies have shown that the brain activity elicited by Aδ-nociceptive input and that which may be elicited by C-nociceptive input can be explained by a similar configuration of cortical generators, thereby suggesting that these responses reflect the activation of a cortical network that is common to the processing of both nociceptive afferents. In agreement with this hypothesis, a number of studies have shown that these brain responses are similarly modulated by different experimental variables such as task relevance and general level of arousal.
Furthermore, several studies have pointed at the similarities between nociceptive evoked potentials and late ‘vertex potentials’, which are brain responses that can be elicited by a stimulus regardless of its sensory modality. Determining whether all or part of the ERP or functional MRI activity which is produced by a nociceptive stimulus reflects brain processes truly specific of the nociceptive system currently constitutes the first objective of my research activity.
Human electrophysiological studies have shown the existence of significant interactions between the central processing of Aδ- and C-nociceptive input but also between the central processing of nociceptive and non-nociceptive somatosensory input. Indeed, reproducible brain responses to C-nociceptors appear to be elicited only if concurrent activation of faster Aδ-nociceptors is avoided. Similarly, reproducible responses to Aδ-nociceptors appear to be elicited only if concurrent activation of non-nociceptive, richly-myelinated Aβ-fibres is avoided. Taken together, these well-documented experimental observations suggest that similar mechanisms condition the occurrence of both Aδ- and C-fibre electrophysiological responses. Gaining some understanding of the mechanisms which underlie these interactions currently constitutes the second objective of my research activity.
Additional information :