Perturbed connectivity of the amygdala and its subregions with the central executive and default mode networks in chronic pain

Abstract

Maladaptive responses to pain-related distress, such as pain catastrophizing, amplify the impairments associated with chronic pain. Many of these aspects of chronic pain are similar to affective distress in clinical anxiety disorders. In light of the role of the amygdala in pain and affective distress, disruption of amygdalar functional connectivity in anxiety states, and its implication in the response to noxious stimuli, we investigated amygdala functional connectivity in 17 patients with chronic low back pain and 17 healthy comparison subjects, with respect to normal targets of amygdala subregions (basolateral vs centromedial nuclei), and connectivity to large-scale cognitive-emotional networks, including the default mode network, central executive network, and salience network. We found that patients with chronic pain had exaggerated and abnormal amygdala connectivity with central executive network, which was most exaggerated in patients with the greatest pain catastrophizing. We also found that the normally basolateral-predominant amygdala connectivity to the default mode network was blunted in patients with chronic pain. Our results therefore highlight the importance of the amygdala and its network-level interaction with large-scale cognitive/affective cortical networks in chronic pain, and help link the neurobiological mechanisms of cognitive theories for pain with other clinical states of affective distress.

Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

“…Both human and animal studies have demonstrated that stress hormones modify BDNF expression, such that there is decreased BDNF expression in the hippocampus and increased expression in the amygdala [94,95,96]. This finding is consistent with recent neuroimaging studies, which have reported significant loss in hippocampal neuroconnectivity with the medial prefrontal cortex [97], and exaggerated amygdalar connectivity with the central executive network (dorsolateral prefrontal cortex and posterior parietal cortex) in individuals with chronic pain compared to healthy controls [98]. Therefore, genetically determined BDNF availability may modify brain connections contributing to the development and maintenance of chronic pain conditions.…”

“…Baliki et al [154] also noted over the same time course that gray matter brain density decreased in patients with low back pain relative to healthy controls. However, adult chronic low back pain patients also tended to have exaggerated amygdalar connectivity with the central executive network (dorsolateral prefrontal cortex and posterior parietal cortex) as compared to healthy controls [98]. Moreover, this greater connectivity has been associated with increased tendencies to engage in catastrophic thinking about pain [98].…”

“…However, adult chronic low back pain patients also tended to have exaggerated amygdalar connectivity with the central executive network (dorsolateral prefrontal cortex and posterior parietal cortex) as compared to healthy controls [98]. Moreover, this greater connectivity has been associated with increased tendencies to engage in catastrophic thinking about pain [98]. In support of this finding, in adolescents with irritable bowel syndrome, disease duration is associated with cortical thickness in bilateral dorsolateral prefrontal cortex and left supramarginal gyri [155].…”

Optimizing Placebo and Minimizing Nocebo to Reduce Pain, Catastrophizing, and Opioid Use: A Review of the Science and an Evidence-Informed Clinical Toolkit

“…While it is unknown whether structural deficits were antecedents or consequences of catastrophizing, their co-occurrence suggests a mutually-reinforcing biobehavioral cycle of pain and potential nocebo-induced hyperalgesia (Blasini, Corsi, Klinger, & Colloca, 2017). Indeed, pain catastrophizing in individuals with chronic pain has been shown to associate with altered neural functioning outside of the context of evoked pain or in vivo catastrophizing (Jiang et al, 2016). Greater pain catastrophizing is associated with altered brain functioning in the default mode network—an over-coupling between the central executive network and the amygdala—that attune the brain to pain (Jiang et al, 2016).…”

“…Indeed, pain catastrophizing in individuals with chronic pain has been shown to associate with altered neural functioning outside of the context of evoked pain or in vivo catastrophizing (Jiang et al, 2016). Greater pain catastrophizing is associated with altered brain functioning in the default mode network—an over-coupling between the central executive network and the amygdala—that attune the brain to pain (Jiang et al, 2016). These findings suggest that pain catastrophizing is associated with neural alterations in individuals with chronic pain that appear to prime their nervous pain signaling systems for future pain.…”