Chronic Pain and the Emotional Brain: Specific Brain Activity Associated with Spontaneous Fluctuations of Intensity of Chronic Back Pain

Abstract

Living with unrelenting pain (chronic pain) is maladaptive and is thought to be associated with physiological and psychological modifications, yet there is a lack of knowledge regarding brain elements involved in such conditions. Here, we identify brain regions involved in spontaneous pain of chronic back pain (CBP) in two separate groups of patients (n ϭ 13 and n ϭ 11), and contrast brain activity between spontaneous pain and thermal pain (CBP and healthy subjects, n ϭ 11 each). Continuous ratings of fluctuations of spontaneous pain during functional magnetic resonance imaging were separated into two components: high sustained pain and increasing pain. Sustained high pain of CBP resulted in increased activity in the medial prefrontal cortex (mPFC; including rostral anterior cingulate). This mPFC activity was strongly related to intensity of CBP, and the region is known to be involved in negative emotions, response conflict, and detection of unfavorable outcomes, especially in relation to the self. In contrast, the increasing phase of CBP transiently activated brain regions commonly observed for acute pain, best exemplified by the insula, which tightly reflected duration of CBP. When spontaneous pain of CBP was contrasted to thermal stimulation, we observe a double-dissociation between mPFC and insula with the former correlating only to intensity of spontaneous pain and the latter correlating only to pain intensity for thermal stimulation. These findings suggest that subjective spontaneous pain of CBP involves specific spatiotemporal neuronal mechanisms, distinct from those observed for acute experimental pain, implicating a salient role for emotional brain concerning the self.

Delayed pain decrease following M1 tDCS in spinal cord injury: A randomized controlled clinical trial

“…For patients with lower pain level, it is possible that the sensorimotor cortex does not show pathophysiological modification or is less alerted when compared to patients with higher pain intensity. Indeed, several neuroimaging studies have demonstrated the correlation between pain intensity and degree of abnormal activity and connectivity within areas of the pain matrix in various chronic pain syndromes [60,64,65]. Future research to identify biomarkers and predictors of tDCS response could help to identify who and why some patients could benefit from this treatment, as well as to develop a patient-tailored stimulation protocol.…”

Neuroimaging as a Tool for Pain Diagnosis and Analgesic Development

“…7,26,27 Activation in the medial prefrontal cortex was reported during ongoing lower back pain, and was correlated with the intensity of the pain. 28 The thalamus is another region affected by chronic pain. Several studies reported a decrease of cerebral blood flow and metabolic rate in the thalamus contralateral to the clinical pain.…”

“…28 However, the increase of the intensity of their clinical pain correlates with activation in the regions observed during acute pain processing (i.e., the somatosensory cortices and the insular cortex). 28 Kulkarni et al 44 also observed differences between ongoing arthritic pain and evoked pain.…”

Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain

“…In humans, different subregions of the PFC have a role in acute pain; the medial prefrontal cortex (mPFC) was found to be involved in signaling the unpleasantness of pain (3); the anterior cingulate cortex mediates the affective component of pain responses (4) and the placebo effect (5); and anticipation of pain is positively correlated with activity in both the anterior cingulate and mPFC (6). Lending support to the hypothesis that chronic pain involves cortical reorganization, functional MRI (fMRI) studies in patients with complex region pain syndrome type I (CRPS-I) and back pain have shown that the patients' real-time rating of perceived intensity of spontaneous pain is associated with novel activity in mPFC (7,8) when compared with activity patterns that correlate with rating of acute pain stimuli. Additionally, studies in humans with CRPS-I and chronic back pain demonstrate impaired performance on emotional decisionmaking tasks such as the Iowa Gambling Task (9), which implies involvement of the mPFC.…”