Corticolimbic anatomical characteristics predetermine risk for chronic pain

Abstract

SEE TRACEY DOI101093/BRAIN/AWW147 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Mechanisms of chronic pain remain poorly understood. We tracked brain properties in subacute back pain patients longitudinally for 3 years as they either recovered from or transitioned to chronic pain. Whole-brain comparisons indicated corticolimbic, but not pain-related circuitry, white matter connections predisposed patients to chronic pain. Intra-corticolimbic white matter connectivity analysis identified three segregated communities: dorsal medial prefrontal cortex-amygdala-accumbens, ventral medial prefrontal cortex-amygdala, and orbitofrontal cortex-amygdala-hippocampus. Higher incidence of white matter and functional connections within the dorsal medial prefrontal cortex-amygdala-accumbens circuit, as well as smaller amygdala volume, represented independent risk factors, together accounting for 60% of the variance for pain persistence. Opioid gene polymorphisms and negative mood contributed indirectly through corticolimbic anatomical factors, to risk for chronic pain. Our results imply that persistence of chronic pain is predetermined by corticolimbic neuroanatomical factors.

The Role of Stress Regulation on Neural Plasticity in Pain Chronification

“…Notably, Melzack [2] proposed that stress played an important role in such pain chronification, and accumulating evidence demonstrated that stress regulation (as indexed by the function of hypothalamic-pituitary-adrenal [HPA] axis) consistently engaged in the development of chronic pain [3–5]. In line with these findings, several brain regions, subserving as key candidates for stress regulation [6–8], have been reported to be involved in the transition from acute to chronic pain, including the amygdala, prefrontal cortex (PFC), and hippocampus [9–12]. Therefore, some previous studies hypothesized that these brain regions, especially within the emotional corticolimbic system, acted as the bridge of pain modulation and stress regulation.…”

“…The corticolimbic system, including amygdala, PFC, and hippocampus, is a powerful neural network that has been suggested to contribute to the transition from acute to chronic pain [12]. Further, both acute and chronic pain profoundly influence this system, which is also known to relate to stress regulation [8], via structural and functional alterations in the related brain regions.…”

Subliminal (latent) processing of pain and its evolution to conscious awareness

“…Within the pain context – two examples may provide insight into these premorbid changes that may be basally present and evolve in time: One set of examples relates to the status of specific regional functional connectivity such as the amygdala-cortical functional connectivity (Vachon-Presseau et al, 2016) or networks involved in endogenous pain modulation (a presumed gateway for increased or decreased responsivity of the pain system) (Staud, 2012; Yarnitsky, 2015). The former may be evaluated in terms of disease development (for example, anxiety disorders (Swartz and Monk, 2014)).…”

Neuroimaging mechanisms in pain: from discovery to translation

“…This was based on structural (ie, white matter) and functional network connectivities (in both cases stronger connectivity in the persistent pain group), with only the structural white matter network connectivity differences remaining constant over 3 years. 115 I have postulated a possible alternative explanation of their data focussing on the issue of subjective relief in response to April 2017 · Volume 158 · Number 4 · Supplement 1 www.painjournalonline.com S117 treatment interventions and the question as to why some patients report no analgesia and therefore remain in persistent pain. 108 Other work by my group has shown that increased activity of baseline reward circuitry in response to evoked pain and increased trait reward responsiveness is correlated with subsequent reports of increased opioid analgesia; perhaps implying that a functional reward system is required to benefit from this treatment intervention.…”