An fMRI study exploring the overlap and differences between neural representations of physical and recalled pain

Abstract

Implementing a recall paradigm without hypnosis, we use functional MRI (fMRI) to explore and compare nociceptive and centrally-driven pain experiences. We posit that a trace of a recent nociceptive event can be used to create sensory-re-experiencing of pain that can be qualified in terms of intensity and vividness. Fifteen healthy volunteers received three levels of thermal stimuli (warm, low pain and high pain) and subsequently were asked to recall and then rate this experience. Neuroimaging results reveal that recalling a previous sensory experience activates an extensive network of classical pain processing structures except the contralateral posterior insular cortex. Nociceptive-specific activation of this structure and the rated intensity difference between physical and recalled pain events allow us to investigate the link between the quality of the original nociceptive stimulus and the mental trace, as well as the differences between the accompanying neural responses. Additionally, by incorporating the behavioural ratings, we explored which brain regions were separately responsible for generating either an accurate or vivid recall of the physical experience. Together, these observations further our understanding of centrally-mediated pain experiences and pain memory as well as the potential relevance of these factors in the maintenance of chronic pain.

Figure 1. Study design for creating a recalled pain experience based on a preceding nociceptive event.

Each block consisted of a six-second, thermal stimulus, either warm, low pain or high pain. The thermal stimulus was produced by an in-house built thermode which could ramp up to the targeted temperature in 1 second (bell shaped-stimulus for illustration purpose only).For the full duration of the thermal stimulus, a verbal visual stimulus “feeling pain” was shown. This was followed by a delay (time-to-test interval) of eleven seconds during which a fixation cross was presented. Subjects were then instructed by means of a visual stimulus “imagine feeling pain” to recall and imagine the preceding thermal event. This recall was performed in the absence of peripheral somatosensory stimulation. After each recalled pain event, subjects used a visual analogue scale (VAS) to rate the intensity and vividness of the “imagined pain” event. (For further details, refer to Materials and Methods.).

Figure 2. Nociceptive specific activity in the posterior insula.

A) Neural activity specific to processing physical pain (high physical pain > recalled high pain). Group contrast, mixed effects, Z = 2.3; p = 0.01, see Table 3 for further details of coordinates. B) Group mean parameter estimates of peak activity during physical and recalled pain describing observed nociceptive specific activation of posterior insula as compared to anterior insula. Error bars represent standard error. C) Timecourse analysis of posterior and anterior insula showing mean signal change across “Feeling pain” and “Imagine feeling pain” events. Insets shows results of (top) posterior insula activity from a contrast of high physical pain > recalled high pain (see Table 3) and (bottom) anterior insula activity as revealed by a conjunction analysis of common activity across the physical and recalled high pain conditions (see Table 5 for further details of coordinates). Error bars represent standard error.

Figure 3. Intensity and recalled pain.

A) Linking nociceptive intensity and therefore posterior insula activity during physical pain with neural activation during subsequent recall. Left: graphical summary of group mean parameter estimates (PE) of percent signal change in posterior insula during high physical pain. Error bars represent standard error. Right: predicted activity during recalled high pain incorporating individual PEs as a regressor. See Table 6 for further details of MNI coordinates. B) Intensity coding during recalled pain. Left: graphical summary of recalled intensity ratings across conditions of imagined stimuli. Error bars represent standard error. Right: Brain regions from a whole brain search whose activity increases with increased perceived intensity of the imagined stimulus and are not seen in the similar analysis performed to explore vividness encoding. Group contrast, mixed effects, Z = 2.3; p = 0.01. See Table 7a for full list of activation with MNI coordinates.