Functional brain response to painful mechanical stimulation and painful stimulation in areas of secondary mechanical hyperalgesia: A meta-analysis

This study evaluated brain activity in response to painful and nonpainful mechanical stimuli within an area of secondary mechanical hyperalgesia (SMH) compared to non-sensitized areas. We performed a meta-analysis summarizing responses to three different types of stimuli. Furthermore, we summarize reported results of contrast maps comparing brain responses to mechanical stimuli in SMH that in non-sensitized regions. We investigated 3 categories of brain responses to 1) nonpainful mechanical stimuli in 226 participants across 16 studies, 2) painful mechanical stimuli in 164 participants across 11 studies, 3) mechanical stimuli in SMH in 84 participants across 7 studies, and 4) contrast maps of brain responses to mechanical stimuli in SMH versus painful mechanical stimuli in 107 participants across 7 studies. We used GingerALE 3.0.2 to create meta-analytic statistical parametric maps. We generated summary Z-maps by subtracting negative maps from positive maps. Maps were Z-value thresholded at 3.29 and a cluster size of 272 mm3. Nonpainful mechanical stimuli activated bilateral parietal operculum (PO), right inferior frontal gyrus (IFG) and inferior parietal lobule. Painful mechanical stimuli activated bilateral PO, bilateral IFG pars opercularis, and deactivation in bilateral superior occipital gyri. Mechanical stimuli in SMH activated bilateral PO, bilateral dorsal anterior insula, left postcentral gyrus and supragenual anterior cingulate cortex. The contrast of mechanical stimuli in SMH versus painful mechanical stimuli included greater activation in right thalamus, left lateral periaqueductal gray, right dorsolateral prefrontal (DLPFC), right Rolandic opercular, bilateral primary somatosensory, anterior midcingulate, and right middle insular cortices. Contrast results revealed greater activation during SMH compared to painful mechanical stimulation in right thalamus, right DLPFC, and left lateral periaqueductal gray. These areas are involved in pain modulation (hyperalgesic and analgesic), while responses in mid insula and mid cingulate cortices are prominent in processing salient and painful stimuli. Neurosurgery Pain Research Institute, Postdoctoral Scholarship (TJM).