The Subjective Experience of Pain

The featured paper is ‘The subjective experience of pain:Where expectations become reality’ by Tetsuo Koyama and colleagues and is freely available here.

In the section leading up to the statement of the aims of the study, the authors construct a simple model of anticipation of pain

1. Mental Representation of pain based on previous experiences

2. Neural basis of mental representation should interact with pain-processing regions in the brain

3. Neural basis of subjective pain should modified by anticipation

The authors then stated the aim of identifying the regions of the brain involved in expectation of pain.

10 volunteers between the ages of 24 and 46 were included in the study and a thermal stimulator was attached to their right leg. Increasing temperatures were delivered to the subjects and the gaps between stimuli indicated the temperature of the stimulus (i.e. there was a big delay for the hotter stimuli and so a very big gap would signal to the subject that they were about to receive a very hot temperature). While the subjects were experiencing these thermal stimuli they were also undergoing fMRI scans with a 1.5T scanner. I wasn’t entirely clear on one part of the paper – the authors state that they wanted to reduce the ‘temporal effects’ over the scanning session by randomly presenting the stimuli. However since time is being used as a signal of stimulus intensity, it is initially difficult to see how the anticipation of pain can be separated from the process of estimating time (i.e were the active brain regions simply measuring time) – although it should be possible for the statistical analysis to separate out the two. However there was also control tasks which were referred to as false blocks in which there was a different relationship between the pain stimulus and the duration of the gap. Thus subtraction of activation patterns between the two tasks should identify those regions measuring pain alone (although this reasoning may not be correct if there are non-summative interactions between pain and duration activation patterns occuring). Pain was measured using visual analogue scales. The FSL functional imaging analysis software package was used and is expanded upon in the data supplement. However the supplement simply states that functional images were mapped to the structural data. As the Insular Cortex is mentioned later in the paper, it is not clear how the location of the Insular Cortex was determined given it’s deeper structure within the brain and difficulties surrounding this as described in Nawata’s paper. Impressively however, the authors also monitored autonomic data within the study. One small point was that I couldn’t find any mention of adjusting for age in the method section.

The authors found that there was an expected increase in physiological parameters such as heart rate with increasing intensity of the pain stimulus and that expected pain ratings increased with duration of the phase of expectation. There were a number of other findings of relevance to the Insula (which can be used in developing a model of the Insular Cortex)

1. Areas with a positive relation to intensity of expected pain included the anterior and posterior insula, secondary somatosensory cortex, supplementary motor area, dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), inferior parietal lobe, cerebellum, thalamus and lentiform nucleus.

2. Areas with a negative relation to intensity of expected pain included ventromedial PFC and posterior cingulate cortex

3. Perception of pain intensity was related to increased activity in the anterior and posterior insula, dorsolateral PFC, ACC, SMA, SI contralateral leg areas, SII.

4. Perception of pain intensity was related to decreased activity in the ventromedial PFC and posterior cingulate

5. A trend that was noted by the authors was that if an area was active in both expectation and pain perception (Insula, ACC, SMA) then the rostral parts had greater activation in the expectation phase while the caudal parts had greater activation with pain perception.

6. If there was a decreased expectation of pain, then the corresponding pain intensity that was experienced decreased (curiously the reverse finding was not true i.e that increased pain expectation resulted in greater pain). This was correlated with decreased activation in the ACC, SI and Insula.

7. Curiously there was little change in heart rate during the expectation phase.

The authors discuss there findings and come up with some interesting models particularly concerning the Insular Cortex.

1. Areas including the PFC, Insula, ACC, Globus Pallidus, Thalamus, Cerebellum were increasingly activated as the intensity of the expected stimulus increased without any corresponding increase in heart rate during the expectation phase which was inferred to mean there was suppression of other areas in the process (e.g of anxiety). They concluded that PFC, Insula and ACC were working with the subcortical areas to

‘support the mental representation of an impending stimulus’.

2. Since mental representations reference previous events there must be involvement of memory circuits. In expectation – the PFC receives input from Amygdala, hippocampus, whilst the ACC and Insula receive afferents from Amygdal and Hippocampus also. They also comment on the interconnectivity of the ACC, Insula and PFC.

3. Integration of Expectations and Afferent information. Expectation representations in the ACC and Anterior insular were suggested to possibly be transmitted to somatosensory regions and they mention a specific pathway of anterior insula to posterior insula to SII to inferior parietal cortex.

4. The authors suggest that the information in 3 can be used in the formation of perceptual sets but that in the case of pain this is a highly parallel process and they suggest widespread recruitment of brain regions.

This is a detailed study elucidating some possible relationships of the Insula to the processing of pain sensations.



The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.


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