Altered Brain Structure and Function Correlate with Disease Severity and Pain Catastrophizing in Migraine Patients

Abstract

To investigate the neuroanatomical and functional brain changes in migraine patients relative to healthy controls, we used a combined analytical approach including voxel- and surface-based morphometry along with resting-state functional connectivity to determine whether areas showing structural alterations in patients also showed abnormal functional connectivity. Additionally, we wanted to assess whether these structural and functional changes were associated with group differences in pain catastrophizing and migraine-related disease variables in patients. We acquired T1-weighted anatomical and functional magnetic resonance imaging scans during rest in human subjects with a diagnosis of migraine and healthy controls. Structural analyses revealed greater left hippocampal gray matter volume and reduced cortical thickness in the left anterior midcingulate in patients compared with controls. We also observed negative associations between pain catastrophizing and migraine disease variables and gray matter in areas implicated in processing the sensory, affective, and cognitive aspects of pain in patients. Functional connectivity analyses showed that migraine patients displayed disrupted connectivity between default mode, salience, cognitive, visuospatial, and sensorimotor networks, which was associated with group differences in pain catastrophizing and migraine-related disease variables in patients. Together, our findings show widespread morphological and functional brain abnormalities in migraineurs in affective, cognitive, visual, and pain-related brain areas, which are associated with increased pain catastrophizing, disease chronicity, and severity of symptoms, suggesting that these structural and functional changes may be a consequence of repeated, long-term nociceptive signaling leading to increased pain sensitivity, mood disturbances, and maladaptive coping strategies to deal with unrelenting pain.

The Dorsolateral Prefrontal Cortex in Acute and Chronic Pain

“…One study that contrasted brain resting cerebral blood flow between two chronic orofacial pain disorders, temporomandibular disorders and trigeminal neuropathic pain, found that both patient groups had increased DLPFC resting cerebral blood flow compared to pain-free controls, suggesting that spontaneous pain is related to DLPFC activity 111 . Other studies have reported lower gray matter volume (GMV) or thinner cortices in the DLPFC in patients with chronic pain, including irritable bowel syndrome 9, 90 , chronic low back pain 3, 85, 92, 110 , migraine 38 , trigeminal neuralgia 35, 66 , chronic post-traumatic headache 65 , and complex regional pain syndrome 26 . In some cases, these structural abnormalities were correlated with pain catastrophizing or other clinical characteristics 38 .…”

“…Other studies have reported lower gray matter volume (GMV) or thinner cortices in the DLPFC in patients with chronic pain, including irritable bowel syndrome 9, 90 , chronic low back pain 3, 85, 92, 110 , migraine 38 , trigeminal neuralgia 35, 66 , chronic post-traumatic headache 65 , and complex regional pain syndrome 26 . In some cases, these structural abnormalities were correlated with pain catastrophizing or other clinical characteristics 38 . These findings are corroborated by magnetic resonance spectroscopy (MRS) studies that have found decreased levels N-acetyl-aspartate (NAA) – a putative measure of neuronal viability – in the DLPFC in chronic back pain 32 and complex regional pain syndrome 33 .…”

Effects of Cognitive-Behavioral Therapy (CBT) on Brain Connectivity Supporting Catastrophizing in Fibromyalgia

“…Given that previous non-neuroimaging CBT studies have identified catastrophizing as a crucial process variable, it seems likely that changes in catastrophizing may contribute critically to the putative “normalization” of brain function that CBT produces. Moreover, several recent fMRI studies have indicated that catastrophizing in patients with functional pain conditions such as fibromyalgia and irritable bowel syndrome is associated with the hyperalgesia that characterizes these conditions, and also with alterations in pain-related brain activation or functional connectivity (27–29). Specifically, Kim et al (27) found that pain-evoked increase in primary somatosensory cortex (S1)-insula connectivity was correlated with catastrophizing – patients with greater PCS scores also demonstrated greater pain-evoked increases in S1-insula connectivity.…”

Lower inhibitory control interacts with greater pain catastrophizing to predict greater pain intensity in women with migraine and overweight/obesity

“…Moreover, recent work among individuals with migraine shows an association between higher levels of pain catastrophizing and brain abnormalities in areas associated with pain processing [19]; the areas involved overlap with those implicated in inhibitory control (i.e., prefrontal cortex; e.g., [11, 12]). Despite these possible links between inhibitory control and pain catastrophizing in migraine, no study has directly explored this potential interaction in relation to migraine pain intensity, duration, and frequency.…”