Disentangling linear and nonlinear brain responses to evoked deep tissue pain

Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Pain (Impact Factor: 5.21). 08/2012; 153(10):2140-51. DOI: 10.1016/j.pain.2012.07.014
Source: PubMed


Pain stimuli evoke widespread responses in the brain. However, our understanding of the physiological significance underlying heterogeneous response within different pain-activated and -deactivated regions is still limited. Using functional magnetic resonance imaging, we evaluated brain responses to a wide range of stimulus intensity levels (1 innocuous, 7 painful) in order to estimate region-specific stimulus-response functions, which we hypothesized could illuminate that region's functional relationship to pain. Linear and nonlinear brain responses to pain were estimated through independent Legendre polynomial transformations of pain ratings within a general linear model. This approach identified at least 5 different, regionally specific activity profiles in the brain. Linearly increasing (eg, primary somatosensory/motor cortex, insulae) and intensity-independent (eg, secondary somatosensory cortex) activation was noted in traditional pain-processing areas, potentially reflecting sensory encoding and all-or-none salience responses, respectively. Multiple activity profiles were seen in areas of the default mode network (DMN): intensity-independent deactivation (eg, posterior cingulate cortex), linearly decreasing (eg, contralateral inferior parietal lobule), and quadratic (U-shaped; eg, medial prefrontal cortex). The latter observation suggests that: (1) different DMN subregions exhibit functional heterogeneity and (2) some DMN subregions respond in a percept-related manner to pain, suggesting closer linkage between the DMN and pain processing than previously thought. Future studies should apply a similar approach using innocuous stimuli of multiple intensities to evaluate whether the response profiles reported here can also be generalized to nonpainful somatosensory processing.

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    • "In general, somatosensory cortical areas and anterior cingulate activity seem to track stimulus intensity, whereas lateral prefrontal and posterior parietal regions do not (Bü chel et al., 2002; Coghill et al., 1999; Davis et al., 1997; Peyron et al., 1999). Brain activity related to perceived magnitude of pain is studied less systematically (Baliki et al., 2009; Johnstone et al., 2012; Loggia et al., 2012; Moulton et al., 2012). Different temporal transformations are observed between stimulus and perception in various brain regions, and the region best related to perceived pain (anterior insula) seems to also reflect perceived magnitude for visual stimuli (Baliki et al., 2009). "
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