Last updated: Fri, Feb 21, 2025
We know that pain is complex. Pain has a location, a duration, an intensity, and some sensory quality that leads us to distinguish, say, an abrasion from a bruise from a burn. (See The Varieties of Pain for a review.) We know from physiological evidence that nociceptive information often converges on particular brain structures.1 This convergence helps to explain how referred pain can occur. Despite the many variations in pain sensation, we nevertheless effortlessly identify them as pain. This section describes how the pain matrix is believed to create this multi-dimensioned experience for us.
S1, the primary somatosensory cortex, is topographically organized and is known to provide location information for inncocuous cutaneous sensation. It is also believed to provide location information for noxious cutaneous sensation. Non-cutaneous somatic sensation and visceral sensation is not as clearly localized in the brain, and hence non-cutaneous somatic and visceral pain is not as clearly localized by the subject experiencing the pain.
Areas of the IC, the insular cortex, are also topographically organized and also participate in the localization of pain sensation.
A 2003 fMRI study compared brain activation under two conditions: the cutaneous chest was heated or the esophagus was stretched to achieve similar levels of pain intensity. The two conditions caused primary activation in differing locations within S1, IC, the motor cortex, and the PFC2. This and similar results suggest that different qualities of painful stimulation may be distinguished through this differential activation of brain regions.
The spinothalamic tract (STT) delivers neural information to the contralateral brain, while other, older tracts may not. (The Ascending Tracts.) Imaging studies of pain show that activation of the primary somatosensory cortex (S1) is contralateral, while activation of the secondary somatosensory cortex (S2) and insular cortex (IC) is bilateral. The laterality of activation of the anterior cingulate cortex (ACC) is difficult to read, because it lies along the midline of the brain. One study has found that, for low-intensity stimuli, brain activity that correlates with intensity is contralateral, while activity that doesn't correlate with intensity occurs in the right hemisphere of the brain.3
While IC activation in pain imaging studies is usually bilateral, electrical stimulation of the IC provokes pain that is perceived as belonging to the contralateral side of the body for the body and trunk, while for the face, the provoked sensation is more bilateral.
These results are consistent with the idea that S1 is important in determining pain location, while the areas with bilateral activation are involved in other aspects of analyzing or defining pain sensation.
A 2009 imaging study showed that activity in an area of the insular cortex (IC) adjacent to the dorsal cortex best reflected the perceived intensity of painful heat. This same area of IC also best reflected the perceived size of bars seen in a visual test unrelated to pain. Activation of this area during the pain studies corresponded exactly to perceived pain intensity for each subject and each stimulus.4
Information about the sequence in which different brain areas attend to a painful stimulus come from EEG and MEG studies, which preferentially read brain areas nearer the skull. (EEG and MEG.)
Fast and slow pain, or first and second pain (Dimensions and Flavors of Pain), occur almost a second apart, primarily because of the difference in transmission speeds of the A and C neurons that are responsible for the first and second impulses. EEG and MEG studies show two activations of S1, S2, and ACC in response to the two impulses.5 First pain seems to activate S1, while second pain activates the ACC. Both signals activate S2.
Innocuous cutaneous stimuli first activate S1, then S2. During painful stimulation, however, S2 is activated before S1. The IC is activated slightly after S2. This suggests that S2 and IC can be considered to be primary receiving areas for nociceptive input.
First pain, which utilizes A neurons and the phylogenetically new STT, provides quick and precise information to allow a quick and precise reaction to a painful event. Second pain activates the brain for a longer time and allows behavioral responses to limit further injury and facilitate recovery.6
A MEG-based study in 2002 compared response to cold and to painful cold. Peak contralateral activation of the IC to cold stimulus occurred after 190 msec. Peak ipsilateral activation occurred after 240 msec. Peak activation of S2 occurred about 100 msec later in each case. Neither cold nor painful cold caused measurable activation of S1, however. These results suggest that cold, painful cold, and tactile stimulus may be processed differently in the brain.7
MRI-based techniques have been used to examine the response of the brain to painful stimuli over time. Subjects were exposed to repetitive painful heat over many seconds and images were taken early in that period and after forty seconds. Subjects perceived the stimulus as more intense and more unpleasant over time. Certain brain areas were active only at the beginning of the extended stimulation: the PFC, part of the ACC, and the anterior IC. Other brain areas were more active during the later scan than in the early scan: the contralateral S1, bilateral S2, parts of the IC and thalamus. The full import of these findings are unclear, except the fact that activation changes over time.8
A 2009 study was able to use fMRI to follow the sequence of brain area activations over the course of an extended painful heat stimulus. Subjects were exposed to a heat stimulus that lasted about 20 seconds. The intensity of the stimulus (amount of heat) was tracked, and the subjects' perception of pain intensity was also tracked. The intensity of the heat stimulus was highest at +10 seconds. The perceived pain intensity was highest at +18 seconds.9
The fMRI imaging was used to measure the amount of oxygen usage in different brain areas over time. The sequence in which the maximum oxygen usage was found was as follows:
The brain areas were also characterized as to how closely they followed the stimulus intensity, versus how closely the followed the perceived pain intensity.
The ACC and the amygdala both showed maximal activity before the heat stimulus came to its maximum at +10 seconds. These areas then can be seen as watching or perhaps predicting the heat stimulus.
Activation of the next group of five areas (thalamus, basal ganglia, dorsal premotor cortex, nociceptive IC, and supplementary motor area) follows the intensity of the heat stimulus most closely, and were most active shortly after the maximum heat stimulus. This group of areas then most-closely tracked the heat stimulus.
The remaining areas showed maximum activation just before the subjects experienced maximum perceived pain. Of these three areas, the magnitude-sensitive portion of the IC and the ventral premotor cortex reflect perceived pain intensity, while the inferior parietal sulcus is believed to have been activated in order for the subjects to report perceived pain intensity to the experimenters.