Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits

Abstract

Chronic pain conditions are associated with abnormalities in brain structure and function. Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies. How brain activity reorganizes with transition from acute to chronic pain has remained unexplored. Here we study this transition by examining brain activity for rating fluctuations of back pain magnitude. First we compared back pain-related brain activity between subjects who have had the condition for ∼2 months with no prior history of back pain for 1 year (early, acute/subacute back pain group, n = 94), to subjects who have lived with back pain for >10 years (chronic back pain group, n = 59). In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group, n = 19) and those in which the back pain persists (persistent acute/sub-acute back pain group, n = 20; based on a 20% decrease in intensity of back pain in 1 year). We report results in relation to meta-analytic probabilistic maps related to the terms pain, emotion, and reward (each map is based on >200 brain imaging studies, derived from neurosynth.org). We observed that brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry. The results demonstrate that brain representation for a constant percept, back pain, can undergo large-scale shifts in brain activity with the transition to chronic pain. These observations challenge long-standing theoretical concepts regarding brain and mind relationships, as well as provide important novel insights regarding definitions and mechanisms of chronic pain.

The Emotional Brain as a Predictor and Amplifier of Chronic Pain

“…The dynamics of corticolimbic reverberating loops depend both on the preexisting limbic brain circuitry and on the reorganization following the inciting event, and these interactions will determine the likelihood of either recovering from or transitioning to chronic pain. chronic pain or transition to chronic pain activates the amygdala in relation to subjective perception of the chronic pain (Baliki et al 2006;Hashmi et al 2013). The mPFC's neuronal activity and morphology change in various animal models of persistent pain (Metz et al 2009;Kiritoshi and Neugebauer 2015).…”

“…The mPFC's neuronal activity and morphology change in various animal models of persistent pain (Metz et al 2009;Kiritoshi and Neugebauer 2015). In humans, the region reflects subjective chronic pain intensity, and its functional connectivity with the NAc is predictive of transition to chronic pain (Baliki et al 2006;Baliki et al 2012;Hashmi et al 2013). Moreover, human evidence now shows that hippocampal intrinsic connectivity and hippocampal cortical connectivity are modified with transition to chronic pain (Mutso et al 2013).…”

5: Mindfulness-based stress reduction as a novel treatment for interstitial cystitis/bladder pain syndrome: A randomized controlled trial

“…The improved self-efficacy scores in the MBSR group suggest MBSR may diminish perceived helplessness associated with the chronic pain of IC/BPS. As opposed to acute pain, which is related to nociceptive signals at the level of tissue damage, chronic pain appears to be processed in regions of the brain associated with emotion and reward [21]. This may explain why therapies that target the bladder are incompletely effective in many patients.…”

Effect of electroconvulsive stimulation on messenger RNA expression in the prefrontal cortex in a rat pain model

“…With respect to chronic pain, it has been suggested that shifting the focus from 'an infringed sensory system' to 'an emotion system' is essential for advancing mechanistic understanding (26). In addition, it is thought that pain arising from damage and inflammation is associated with mental and physical stress (27).…”