Structural Brain Anomalies and Chronic Pain: A Quantitative Meta-Analysis of Gray Matter Volume

Abstract

The diversity of chronic pain syndromes and the methods employed to study them make integrating experimental findings challenging. This study performed coordinate-based meta-analyses using voxel-based morphometry imaging results to examine gray matter volume (GMV) differences between chronic pain patients and healthy controls. There were 12 clusters where GMV was decreased in patients compared with controls, including many regions thought to be part of the “pain matrix” of regions involved in pain perception, but also including many other regions that are not commonly regarded as pain-processing areas. The right hippocampus and parahippocampal gyrus were the only regions noted to have increased GMV in patients. Functional characterizations were implemented using the BrainMap database to determine which behavioral domains were significantly represented in these regions. The most common behavioral domains associated with these regions were cognitive, affective, and perceptual domains. Because many of these regions are not classically connected with pain and because there was such significance in functionality outside of perception, it is proposed that many of these regions are related to the constellation of comorbidities of chronic pain, such as fatigue and cognitive and emotional impairments. Further research into the mechanisms of GMV changes could provide a perspective on these findings. Perspective Quantitative meta-analyses revealed structural differences between brains of individuals with chronic pain and healthy controls. These differences may be related to comorbidities of chronic pain.

Reward responsiveness in patients with chronic pain

“…If acute pain does not affect the hedonic experience of rewards (Gandhi et al, 2013), reduced reward responsiveness in PCPs could be a consequence of the long-term effects of pain or a marker of chronic pain vulnerability (Denk et al, 2014). The trend towards reduction in nucleus accumbens volume concurs with a previous study that showed reduction in its size as pain became chronic and in a meta-analyses of morphometric studies on PCPs (Baliki et al, 2012;Smallwood et al, 2013). However, one study on rheumatoid arthritis patients found increased nucleus accumbens volume (Wartolowska et al, 2012).…”

“…Ventral striatum grey matter density has been shown to correlate with both a combination score of personality traits that included reward drive and reward responsiveness and degree of placebo analgesia in healthy controls (Schweinhardt et al, 2009). Furthermore, a systematic meta-analysis of brain structure in PCP demonstrated reduced volume in the area of the nucleus accumbens (Smallwood et al, 2013), and nucleus accumbens grey matter density has been shown to decrease after the onset of chronic back pain (Baliki et al, 2012). The biological mechanisms underlying the observed volume change are unknown, but chronic pain induced changes in several neurotransmitter systems (D'Angio et al, 1987;Li et al, 2001;Chang et al, 2014;Schwartz et al, 2014), and connectivity with other basal ganglia as well as cortical regions (Mansour et al, 2013;Chang et al, 2014) may play a role.…”

Structural Brain Alterations in Community Dwelling Individuals with Chronic Joint Pain

“…Previous studies that examined structural brain alterations in chronic pain focused on a variety of pain phenotypes, such as migraine, back pain, osteoarthritis, and fibromyalgia. [6][7][8][9][10][11][12][13][14][15] Typically, the study size was small; the largest studies included approximately 100 subjects. The small sample sizes of these studies led to a modest statistical power, thereby influencing the reproducibility of the results.…”

Effects of long-term acupuncture treatment on resting-state brain activity in migraine patients: A randomized controlled trial on active acupoints and inactive acupoints

“…The insula is a functionally heterogeneous brain region that participates in pain perception, emotional processing and interoception. It was commonly revealed that there was a difference in gray matter volume in chronic pain patients compared with healthy controls [47]. The insular networks were found to be altered by migraine headache [54,55], and our research team demonstrated that migraine patients have dysfunctional connectivity involved with the insula [8,39].…”

“…Based on our results, we detected that a long course of acupuncture treatment on active acupoints affected the hippocampus, which is associated with cognitive components of pain processing, as well as a major component of the human brain that links affective states with memory processing. The hippocampus was described as having increased gray matter volume in patients suffering chronic pain in a meta-analysis [47], and this was confirmed in a recent migraine study [6]. It seems to frequently participate in the central effects of acupuncture.…”