Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density

By Apkar Vania Apkarian, Y. Sosa, Sreepadma Sonty, R. Levy, R. Harden, Todd B. Parrish, D. Gitelman. Journal of Neuroscience, 2004

1,403 citations recorded by the source corpus.

The role of the brain in chronic pain conditions remains speculative. We compared brain morphology of 26 chronic back pain (CBP) patients to matched control subjects, using magnetic resonance imaging brain scan data and automated analysis techniques. CBP patients were divided into neuropathic, exhibiting pain because of sciatic nerve damage, and non-neuropathic groups. Pain-related characteristics were correlated to morphometric measures. Neocortical gray matter volume was compared after skull normalization. Patients with CBP showed 5-11% less neocortical gray matter volume than control subjects. The magnitude of this decrease is equivalent to the gray matter volume lost in 10-20 years of normal aging. The decreased volume was related to pain duration, indicating a 1.3 cm3 loss of gray matter for every year of chronic pain. Regional gray matter density in 17 CBP patients was compared with matched controls using voxel-based morphometry and nonparametric statistics. Gray matter density was reduced in bilateral dorsolateral prefrontal cortex and right thalamus and was strongly related to pain characteristics in a pattern distinct for neuropathic and non-neuropathic CBP. Our results imply that CBP is accompanied by brain atrophy and suggest that the pathophysiology of chronic pain includes thalamocortical processes.

Subfields: Cell Biology, Pharmacology, Physiology

View Paper: https://www.semanticscholar.org/paper/4d0a3f199a1331cf5b345e5b974c2694e5547f69

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Citations in the corpus

Chronic pain may change the structure of the brain. (2008, methodology): “using sophisticated morphometric analysis methods in 17 patients suffering from chronic back pain demonstrated brain atrophy and suggested that the pathophysiology of chronic pain includes thalamo-cortical processes [3].”
Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. (2013, positive): “We followed brain properties of back pain for 1 year, as (i) it is one of the most prevalent clinical conditions that becomes chronic; and (ii) functional and anatomical reorganization, as well as their partial reversal with adequate therapy, are best characterized in this condition (Apkarian et al.”
Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics (2008, background): “…changes in the DMN activity could be related to symptoms (other than pain) commonly exhibited by chronic pain patients, including depression and anxiety, sleep disturbances, and decision-making abnormalities (Apkarian et al., 2004a), which also significantly diminish their quality of life.”
Pain and the brain: Specificity and plasticity of the brain in clinical chronic pain (2010, background): “tial morphometric study and a number of subsequent studies demonstrate that specific regional gray matter decreases correlate with duration of chronic pain, its intensity, and even the interaction between both factors [7,40,57], suggesting that the properties of the clinical conditions are influenci”
Differential distribution of voltage‐gated calcium channel alpha‐2 delta (α2δ) subunit mRNA‐containing cells in the rat central nervous system and the dorsal root ganglia (2005, background): “While some pathological changes have been found in the cortex and the thalamus in neuropathic pain (Apkarian et al., 2004; Weigel and Krauss, 2004), it is surprising to find that 2 -1 and 2 -2 mRNA expression is low in the somatosensory relay nuclei in the thalamus.”
Do we need a third mechanistic descriptor for chronic pain states? (2016, background): “Importantly, these functional changes have in many instances been related to pain severity.(1,31,41,43) Therefore, while acknowledging these limitations in the current and the proposed pain terminology, there remains a rationale for using the new descriptor to distinguish patients with altered nocic”
Differential aging of the brain: patterns, cognitive correlates and modifiers. (2006, neutral): “Chronic back pain, a known stressor, was associated with reduced prefrontal and thalamic density, ‘‘an equivalent of 10–20 years of normal aging’’ (Apkarian et al., 2004).”
Neurobiological Mechanisms of the Placebo Effect (2005, background): “, dorsolateral prefrontal atrophy in chronic pain patients (Apkarian et al., 2004)] may explain the typically lower rates of placebo responding in the more persistent or severe forms of various illnesses.”
Role of the Prefrontal Cortex in Pain Processing (2018, background): “volume in bilateral DLPFC, as well as the right thalamus, which is equivalent to the gray matter volume lost in 10– 20 years of normal aging [137].”
Towards a theory of chronic pain (2008, positive): “In the discussion of this study we suggested ‘‘regional atrophy dictates the brain activity observed in chronic pain, and it may explain the transition from acute to chronic pain’’ (Apkarian et al., 2004b).”
Descending pain modulation and chronification of pain (2014, neutral): “…negative emotional states associated with chronic pain not only exacerbate physiological pain sensitivity [32 ■■ ] but also increase the incidence of comorbidities such as depression, anxiety, sleep disturbance, decision-making abnormalities and can even increase the risk for suicide [33,34 ■ ].”
The cerebral signature for pain perception and its modulation. (2007, background): “It is perhaps important to note that the prefrontal cortex (specifically the dorsolateral PFC) is a site of major neurodegeneration and potential cell death in chronic pain patients (Apkarian et al., 2004b).”