Painis an essential part of everyday human life, ensuring that people don’t heavilywound themselves and indicating that there is a problem in the one’s body.However pain, and especially chronic pain, can also be a, sometimesdebilitating, problem in itself. Furthermore, our current methods to deal withpain can be addictive and not always helpful. Therefore, pinpointing the causeof pain within the human brain could revolutionize the pain response system byenabling the provision of targeted pain-response mechanisms that numb the painwithout the large side effects or addictiveness of drugs such as morphine.However, if pain is a more complicated, dispersed reaction within the brain,the production of methods to control pain would be similarly more complicated.
Thus, determining the method of pain response within the brain has direct,human impacts. Researchershave long hypothesized that there exists a “pain matrix” that (is the primaryarea that) codes primarily for pain responses. However, there is a debatewithin the neuroscience community regarding whether this pain matrix onlyencodes painful stimuli or if it also encodes other non-pain, salient, andsomatosensory stimuli.
Additionally, due to its simplicity and usefulness thehypothesis of having a pain-specific region very seductive meaning that theneuroscience community may have assumed for the pain matrix to exist withoutvery compelling evidence. Recent articles have been produced arguing both sidesand there also exist critiques of articles arguing for a specific area of thebrain encoding pain. For this reason, it is important and pertinent to lookinto the existence of a pain matrix within the brain. Evidencefor a Pain-only Encoding Pain MatrixOnestudy by Baliki et al. looked at the location of pain perception within thebrain and the difference in activation due to pain stimuli of different levels.
Using fMRI, analyzed with blood oxygenated level-dependent signal, on pain andvisual stimuli, fourteen people were asked to either estimate the magnitude ofa painful stimulus based or the length of visual stimulus. The pain stimuliwere related to increased brain activity in a large portion of the brain, specifically activating thebilateral anterior insula, amygdalae, thalami, basal ganglia, and anteriorportions of anterior commissure as well as the ventral striatum much more thanthe visual stimuli (1). Additionally, both stimuli activated the bilateralinsula, dementia pugilistica, ventral posterior nucleus, posterior parietalcortex, and medial temporal cortices (likely activated as both of these stimulihad a visual component), and had midline activations in the middle portions ofthe anterior commissure andsupplementary motor area (1). These results indicated that, although not allareas that coded for pain were specific to pain, part of the insular cortex wascoded specifically for painful activity (1). However, it was simultaneouslyfound that, with regards to activation related to extracting estimated sizes,the pain and visual stimuli activated the same regions (indicating that thereare specific regions that code for size estimates) (1). This study’s smallnumber of subjects as well as its lack of a different salient cue with whichthe pain response could be compared leads to its findings holding slightly lesssignificance.
Another recent study by Segerdahl et al.specifically implicated the posterior insula as an area specific to pain usingarterial spin-labeling quantitative perfusion imaging and MRI. This study usedseventeen subjects, scanned in two phases. First, the subjects scanned at abaseline for seven minutes, followed by being scanned for twenty eight minuteswhile capsaicin cream was applied (to stimulate pain)–the onset period–,seven of which were at the pain peak–the peak period–and then being taken outof the room. In the second phase (directly following the break at the end ofthe first phase), the patients were scanned first without any adjustments forseven minutes–the habituation period–, then with a warm water bottle appliedto the site upon which the capsaicin was applied for seven minutes–therekindle period–, and finally with a cold water bottle applied to the siteupon which the capsaicin was applied for seven minutes–the relief period.Throughout the experiment, pain ratings were verbally taken. These same periodswere repeated using vibration stimuli (salient stimuli) instead of pain stimulifor the purpose of determining if the activated areas of the brain wereactivated due to saliency or pain. This study found that the dorsal posteriorinsula specifically coded for pain response (and not other somatosensoryresponses), making it one of the first studies to strongly come out statingspecifically that one area of the brain encoded only for pain responses (2).
Evidence Against a Pain-only EncodingPain MatrixDueto the high claims of Segerdahl et al.’s article, the neuroscientific communityhighly critiqued the methods of the article and put the results into question.The main problems they found with the article are as follows: (1) there is notenough evidence in the article that the control stimulus was as salient as thepain stimulus (3), (2) the intensity of the control stimulus, unlike that ofthe pain stimulus, did not vary with time, not allowing for the response to bemeasured against the intensity of the stimulus (3), (3) not enough control subjects were used(4), (4) there were no direct comparisons between the control and the pain (4),(5) the researchers looked for a specific “spot” dedicated to pain, which isquestionable due to the large variability in “brain maps” between people (4),and (6) the researchers neglected the wide body of research implying that painis, like most other bodily sensations, coded throughout the brain (4).
Ina study similarly comparing a vibratory, non-pain stimulus to a painful heatstimulus (in this case, with the addition of a neutral control), both the painand control stimuli activated similar regions of the primary and, to a lesserextent, secondary somatosensory cortices. However, the pain stimulus activated”a number of cortical and subcortical areas-including anterior cingulatecortex, SMA, anterior insula, and basal thalamus-all contralateral to thestimulated arm” (5). In general, the pain and vibration conditions activatedsimilar regions except for the activation of the anterior portion of thecontralateral insular cortex (5).
The researchers reached the conclusion thatpain produces distributed activation. The pain stimulation was found to be”more widely dispersed across both cortical and thalamic regions” than that ofthe control stimulation (5). This research used PET scans alongside ratings ofstimuli from 1 to 100, with 50 being the pain threshold and 100 being extremepain. While this study found different results than Segerdahl et al.’s study,it suffers from similar problems: the painful stimuli applied were more salientthan the vibratory, non-painful stimuli and there were few (in this case evenfewer-only 9) subjects. This study also brought up a separate potentialcomplicating factor for the research: patients feel anxiety prior to theapplication of the stimuli. This study used the control (no stimulus) tomitigate this problem, but this should still be noted as a potential reason forsome of the study’s results. Ina different study, Mouraux et al.
investigated if any parts of the pain matrixwere activated only by pain. This study took fMRI data, analyzed with bloodoxygenated level-dependent signal, on people experiencing painful stimuli,other somatosensory stimuli, auditory stimuli, and visual stimuli duringstimulation and rating periods (of 8 and 2 minutes in duration respectively).The study additionally rated the saliency of the four stimuli, finding that thepainful stimuli were 20% more salient than the non-painful stimuli (all ofwhich had approximately the same levels of saliency). While the majority of theareas activated similar areas of the brain, the somatosensory areas activatedadditionally areas of the brain (located in the post-central gyrus) (6).Additionally, after separating the people into two groups and giving them moreor less salient stimuli, the researchers found that the activation was morecorrelated to the saliency of the response than whether the response was a painresponse (6). All stimuli tested activated the thalamus, secondarysomatosensory cortex, the insula, and the anterior cingulate cortex in very similarways (6). In general, the researchers took this data to mean that the painmatrix actually processes all somatosensory stimuli, not just pain stimuli (6).They also concluded that due to their findings about the saliency of thestimuli, “the “pain matrix” is partly, if not entirely, related to bottom–upcognitive processes involved in saliency detection, arousal, and/or attentionalcapture” (6).
Despite these rigorousfindings, this study also faces the problem of having very few participants (inthis case, fourteen people).ConclusionHavingevaluated the data both supporting and against a pain-specific part of thebrain, I find the evidence for a distributed network of pain-coding areas morecompelling. The studies that found that painful and nonpainful stimuli werecoded in similar ways had, to me, better methodologies–as they used more andbetter non-pain stimuli to measure the pain stimuli against–and were larger innumber. That the main study showing that pain was specifically coded in onearea had multiple, valid criticisms also implies that the theory of specificareas for pain is not fully true. Additionally, the acquisition of datasupporting the theory (that painful stimulation is not the only stimulationthat activates the pain matrix) occurs in multiple papers not specificallyinvestigating this information, lending more credence to this theory. Thistheory additionally makes intuitive sense after learning about the fundamentalinterconnectedness of the brain.
Additionally, it seems that more recentstudies have argued against against the existence of a pain-encoding specificregion than have argued against it. This falls in line with the shiftingconception of the brain from that with regions that all have very specific andunique functions to that with regions working together to encode specificstimuli.Withregards to the general methods of the studies, I found the use of vibrotactilestimulation as either a control for or a comparison to pain stimulation to beinteresting, but not fully understandable as none of the articles explained thereason for this useage.
That the one study comparing salience between differentstimulation types found that pain stimulation was non-negligibly more salientthan other somatosensory stimulation leads me to question if vibrotactilestimulation is a good counterweight to painful stimulation. Therefore, I hopethat more studies are conducted in this area specifically using more salientnon-painful stimulations. I also found the studies in which different levels ofsalience were studied to be of particular interest and use.
Especiallyconsidering that the primary question regarding the coding of the pain matrixis whether it codes for pain or salience, differentiating between levels ofstimulus and levels of activity within this region is of large importance. Inaddition to more studies of this nature, having more studies with a largernumber of participants would allow for a larger ability to determine whetherthe data gathered is generalizable to the whole population.