Sex similarities and differences in pain-related periaqueductal gray connectivity

P.A.I.N. Group, McLean Hospital, Belmont, MA, USA.
Pain (Impact Factor: 5.21). 12/2011; 153(2):444-54. DOI: 10.1016/j.pain.2011.11.006
Source: PubMed


This study investigated sex similarities and differences in pain-related functional connectivity in 60 healthy subjects. We used functional magnetic resonance imaging and psychophysiological interaction analysis to investigate how exposure to low vs high experimental pain modulates the functional connectivity of the periaqueductal gray (PAG). We found no sex differences in pain thresholds, and in both men and women, the PAG was more functionally connected with the somatosensory cortex, the supplemental motor area, cerebellum, and thalamus during high pain, consistent with anatomic predictions. Twenty-six men displayed a pain-induced increase in PAG functional connectivity with the amygdala caudate and putamen that was not observed in women. In an extensive literature search, we found that female animals have been largely overlooked when the connections between the PAG and the amygdala have been described, and that women are systematically understudied with regard to endogenous pain inhibition. Our results emphasize the importance of including both male and female subjects when studying basic mechanisms of pain processing, and point toward a possible sex difference in endogenous pain inhibition.

19 Reads
  • Source
    • "Chronic pain is a complex experience that involves several neural networks tied to sensation, motor activity, cognition, and emotion . Brain regions often associated with the pain experience include the primary and secondary somatosensory cortex (S1 and S2), spinal cord, thalamus, insula, anterior cingulate cortex, prefrontal cortex [3] [60] [78], midbrain areas including the periaqueductal gray [44] and cerebellum [52], and subcortical structures including the hippocampus, basal ganglia, and amygdala [9] [48] [65] [72]. There is a growing interest in the cognitive and emotional aspects of pain [10] with the amygdala emerging as a key region of interest [72]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-gender matched controls before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared to controls, with differences predominantly in the left amygdala in the pre-treated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy controls from Time 1 to Time 2 (treatment effects); (4) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related scores and (5) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity following an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.
    Pain 05/2014; 155(9). DOI:10.1016/j.pain.2014.05.023 · 5.21 Impact Factor
  • Source
    • "Neuroimaging research of pain processing is growing tremendously, with the primary and secondary somatosensory cortex (S1 and S2), spinal cord, thalamus, insula, anterior cingulate cortex, and prefrontal cortex consistently identified (Apkarian et al., 2005; Peyron et al., 2000; Tracey, 2008). Emerging imaging research also implicates midbrain areas (e.g., periaqueductal gray) (Linnman et al., 2011), the cerebellum (Moulton et al., 2010), and subcortical structures including the hippocampus, basal ganglia, and amygdala (Borsook et al., 2010; Schweinhardt and Bushnell, 2010). While a number of studies show amygdala activation, few have focused on the area in human imaging as it relates to pain and analgesia (Upadhyay et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The amygdala, a small deep brain structure involved in behavioral processing through interactions with other brain regions, has garnered increased attention in recent years in relation to pain processing. As pain is a multidimensional experience that encompasses physical sensation, affect, and cognition, the amygdala is well suited to play a part in this process. Multiple neuroimaging studies of pain in humans have reported activation in the amygdala. Here, we summarize these studies by performing a coordinate-based meta-analysis within experimentally induced and clinical pain studies using an activation likelihood estimate analysis. The results are presented in relation to locations of peak activation within and outside of amygdala subregions. The majority of studies identified coordinates consistent with human amygdala cytoarchitecture indicating reproducibility in neuroanatomical labeling across labs, analysis methods, and imaging modalities. Differences were noted between healthy and clinical pain studies: in clinical pain studies, peak activation was located in the laterobasal region, suggestive of the cognitive-affective overlay present among individuals suffering from chronic pain; while the less understood superficial region of the amygdala was prominent among experimental pain studies. Taken together, these findings suggest several important directions for further research exploring the amygdala's role in pain processing. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Human Brain Mapping 02/2014; 35(2). DOI:10.1002/hbm.22199 · 5.97 Impact Factor
    • "Pain is commonly viewed as a sensation with multiple components, which are shaped by a combination of cultural, psychological and biological factors[12]. Low back pain of longer duration and increased severity causes cognitive impairments beyond the feeling of pain, which include depression, anxiety, sleeping disturbances and decision-making abnormalities[34]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Functional magnetic resonance imaging studies have shown that the insular cortex has a significant role in pain identification and information integration, while the default mode network is associated with cognitive and memory-related aspects of pain perception. However, changes in the functional connectivity between the default mode network and insula during pain remain unclear. This study used 3.0 T functional magnetic resonance imaging scans in 12 healthy subjects aged 24.8 ± 3.3 years to compare the differences in the functional activity and connectivity of the insula and default mode network between the baseline and pain condition induced by intramuscular injection of hypertonic saline. Compared with the baseline, the insula was more functionally connected with the medial prefrontal and lateral temporal cortices, whereas there was lower connectivity with the posterior cingulate cortex, precuneus and inferior parietal lobule in the pain condition. In addition, compared with baseline, the anterior cingulate cortex exhibited greater connectivity with the posterior insula, but lower connectivity with the anterior insula, during the pain condition. These data indicate that experimental low back pain led to dysfunction in the connectivity between the insula and default mode network resulting from an impairment of the regions of the brain related to cognition and emotion, suggesting the importance of the interaction between these regions in pain processing.
    Neural Regeneration Research 01/2014; 9(2):135-42. DOI:10.4103/1673-5374.125341 · 0.22 Impact Factor
Show more