The Lateral Prefrontal Cortex Mediates the Hyperalgesic Effects of Negative Cognitions in Chronic Pain Patients

Abstract

While high levels of negative affect and cognitions have been associated in chronic pain conditions with greater pain sensitivity, the neural mechanisms mediating the hyperalgesic effect of psychological factors in patients with pain disorders are largely unknown. In this cross-sectional study, we hypothesized that 1) catastrophizing modulates brain responses to pain anticipation, and that 2) anticipatory brain activity mediates the hyperalgesic effect of different levels of catastrophizing, in fibromyalgia (FM) patients. Using functional Magnetic Resonance Imaging, we scanned the brains of 31 FM patients exposed to visual cues anticipating the onset of moderately intense deep-tissue pain stimuli. Our results indicated the existence of a negative association between catastrophizing and pain-anticipatory brain activity, including in the right lateral prefrontal cortex (IPFC). A bootstrapped mediation analysis revealed that pain-anticipatory activity in lateral prefrontal cortex (IPFC) mediates the association between catastrophizing and pain sensitivity. These findings highlight the role of IPFC in the pathophysiology of FM related hyperalgesia, and suggest that deficits in the recruitment of pain-inhibitory brain circuitry during pain-anticipatory periods may play an important contributory role in the association between various degrees of widespread hyperalgesia in FM and levels of catastrophizing, a well validated measure of negative cognitions and psychological distress. Perspective This article highlights the presence of alterations in pain-anticipatory brain activity in FM. These findings provide the rationale for the development of psychological or neurofeedback-based techniques aimed at modifying patients' negative affect and cognitions towards pain.

Dyspnea catastrophizing and neural activations during the anticipation and perception of dyspnea

“…However, we did not observe correlations of dyspnea catastrophizing with activations in further brain areas that have been reported in some of these studies, including the insula, amygdala, prefrontal cortex, or cerebellum (Cottam et al, ; Gracely et al, ; Mathur et al, ; Seminowicz & Davis, ). Furthermore, we did not find negative correlations between catastrophizing scores and brain activations, which were reported in two studies using pain stimuli and included the amygdala, prefrontal areas, and sensory cortices (Loggia et al, ; Seminowicz & Davis, ). In addition, neither during the anticipation nor during the perception of dyspnea were significant correlations of dyspnea catastrophizing observed with activations in insula and amygdala, although these areas were activated in previous studies during anticipated and perceived dyspnea (Davenport & Vovk, ; Evans, ; Faull et al, ; Herigstad et al, ), including the original study of Subsample 2 (Stoeckel et al, ).…”

The Role of Psychosocial Processes in the Development and Maintenance of Chronic Pain

“…In addition, we recently reported that impaired activity in regions of the prefrontal cortices mediated the association between catastrophizing and hyperalgesia in patients with FM. 144 This effect was observed even after statistically controlling for patients’ degree of depressive symptomatology, which is significantly positively correlated with catastrophizing scores. Finally, psychosocial and behavioral interventions that target cognitive processes have been shown to reverse these functional and structural brain changes over the course of just months.…”

“…However, even when controlling for some of these related factors, catastrophizing often retains significant unique, predictive influence (though it is true that no published studies, to our knowledge, control for every other variable listed here). For example, after statistically adjusting for indices of depression and anxiety, catastrophizing remained significantly associated with such diverse outcomes as return to work 77;217 , pain-related physical disability 94 , risk for prescription opioid misuse 155;156 , brain responses to a noxious stimulus 79;144 , pain intensity 8 , pain tolerance 226 , and suicidal ideation 62 . Moreover, catastrophizing likely interacts with other processes such as social support 26 .…”

Negative mood influences default mode network functional connectivity in patients with chronic low back pain: implications for functional neuroimaging biomarkers

“…Factors that affect pain ratings and concomitant brain activity include mood [6,72,78,82], recall of autobiographical painful experiences [22,36,40], social support/distraction [11,21,23,87], and expectations of pain intensity/relief [19,39,47,67,86]. Given that such factors have been widely demonstrated to influence pain perception and its neural correlates, it is likely that these variables will similarly impact functional neuroimaging pain biomarkers.…”