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Tuesday, June 6, 2023

Chronic Low Back Pain May Lead to Gray Matter Atrophy

Brent Brookbush

Brent Brookbush


Research Review: Chronic Low Back Pain May Lead to Gray Matter Atrophy

By Stefanie DiCarrado DPT, PT, NASM CPT & CES

Edited by Brent Brookbush DPT, PT, COMT, MS, PES, CES, CSCS, ACSM H/FS

Original Citation: Apkarian, A.V., Sosa, Y. Sonty, S., Levy, R.M., Harden, R.N., Parrish, R.B., and Gitelman, D.R. (2004) Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. The Journal of Neuroscience. 24 (46): 10410-10415 ARTICLE

Chronic low back pain may be associated with gray matter atrophy

Why is this relevant?: Low back pain is a common complaint among various populations (1). Meucci, et. al (2015) found that 4.2% of individuals aged between 24 and 39 years, 19.6% between ages 20 and 59 years, and in 25.4% of individuals over 60 years suffered from chronic low back pain (CBP) (2). This study correlates changes in grey matter density with CBP. If there is a link between CBP (lasting longer than 6 months) and grey matter atrophy, greater emphasis should be placed on prevention and early access to rehabilitation to reduce not only physical damage but neurological damage as well.

Study Summary

Study Design Case-controlled Descriptive Study
Level of Evidence Level IV: Well designed case-controlled study
Subject Demographics
  • Age:
    • NeuroCBP no flow MRI: 43.3 + 12.4
    • Control no flow MRI: 42.3 + 10.0
    • NeuroCBP fast MRI: 38.0 +12.1
    • Control fast MRI: 43.8 + 6.8
    • NonNeuroCBP no flow MRI: 47.0 +12.6
    • Control no flow MRI: 45.5 + 14.5
    • NonNeuroCBP fast MRI: 38.0 +12.1
    • Control fast MRI: 40.0 + 11.9

  • Gender (control groups had equal numbers)
    • NeuroCBP no flow MRI: 2 females, 5 males
    • NeuroCBP fast MRI: 4 females, no males
    • NonNeuroCBP no flow MRI: 7 females, 3 males
    • NonNeuroCBP fast MRI: 3 females, 2 males

  • Characteristics: Not specified
  • Inclusion Criteria: primary source of unrelenting pain for > 1 year in the lumbosacral region (including buttocks and thighs), with & without radiating pain into the leg
  • Exclusion Criteria: Not specified
Outcome Measures
  • Prefrontal, thalamic, lateral ventricular gray matter volume
  • Whole brain neocortical gray matter volume (excludes cerebellum, brainstem, & deep gray matter)
  • CBP
    • Prefrontal
      • Dorsolateral prefrontal cortext (DLPFC)
        • With neurogenic pain (NeuroCBP): 27% decrease in density
        • Non-neurogenic pain (NonNeuroCBP): 14% decrease in density
    • Lateral ventricles: 21.1 + 8.2 cm³
    • Thalamus
      • R anterior thalamus: Statistically significant decrease in density

    • Whole brain: 528 +44 cm³
      • With age and gender correction: 590 + 28 cm³
  • Controls
    • Prefrontal: data not provided
    • Lateral ventricles: 20.5 + 7.6 cm³
    • Thalamus: data not provided
    • Whole brain: 559 + 42 cm³
      • With age and gender correction: 663 + 27 cm³
  • Comparison
    • Prefrontal
      • Statistically significant decrease in CBP
      • Statistically significant differences between neurogenic CBP and non-neuro CBP
      • Density for all CBP significantly negatively correlated with pain measures, age, & gender
      • Density for NeuroCBP predicted by pain intensity, duration & negative affect (feelings)
      • Density for NonNeuroCBP predicted by pain intensity, duration, sensory, & negative affect

    • Lateral Ventricle
      • No difference between the groups
      • CBP: Significant positive correlations between ventricle size and pain intensity, sensory and negative affect

    • Thalamic
      • Density for all CBP significantly negatively correlated to pain duration

    • Whole brain
      • Statistically significant 5.4% reduction in density in CBP group (skull-normalized, SIENAX analysis)
      • Statistically significant 5.9% reduction in density in CBP group (VBM regional analysis)
      • Statistically significant 11% reduction in density in CBP group when data was corrected for age and gender differences
      • Gray matter volume correlated with age in both groups
      • Pain duration found as "significant predictor" in NeuroCBP (0.2% decrease per year of pain)
Conclusions Chronic pain can alter activity in the brain and lead to atrophy within pain centers. It is important to seek medical assistance early in the pain process and target not only the painful tissue, but the movement impairment that injured the tissue to fully eradicate pain and further loss of tissue.
Conclusions of the Researchers Atrophy in certain areas of the brain may dictate the properties of the pain experienced. Over-excitation of the tissue could lead to overuse atrophy within the pain centers. If treated early enough, the painful condition is likely to reverse or minimize any subsequent brain tissue damage.

A. Bilateral gray matter density reduction highlighted B. Decreased thalamic gray matter density highlighted

Review & Commentary:

This study is compelling, observing the effect of chronic pain on the brain, and further examining the effects of neuropathic versus non-neuropathic pain, on brain atrophy. The authors implemented a strong methodology with a clear definition of chronic low back pain, along with the diagnosis guidelines used by the experienced clinicians in the study. The study did not seek to identify the cause of pain, only that the individuals had pain fitting certain neuropathic or non-neuropathic criteria. Neuropathic subjects experienced significant radiculopathy along with paresthesias, or reduced straight leg raise range of motion, with decreased lower extremity strength, sensation, and/or reflexes as defined by the International Association for the Study of Pain (IASP) criteria (for which the authors provided citations). The authors provided detailed descriptions of MRI parameters, subjective questionnaires for pain, anxiety, and depression, as well as brain morphometry software and citations for validation. The researchers collected information pertaining to medications used by the subjects, as the medication themselves could impact brain morphometry. This article explored a complex relationship between subjective feelings of pain and objectively measurable brain tissue changes; the authors should be applauded for explaining the concepts clearly.

Perhaps the most interesting prose in this publication is the discussion regarding the relationship between the atrophied sections of the brain, and their function in response to pain. As one ages brain tissue normally atrophies at a rate of 0.5% per year, whereas atrophy caused by chronic back pain (CBP) has a rate of 5-11% per year of pain. The authors did note that only 18% of whole brain atrophy was attributed to pain duration, and felt that genetics and lifestyle may also contribute. Regionally, atrophy in the dorsal lateral prefrontal cortex (DLPFC) was highly related to pain characteristics: 40% related in NeuroCBP and 80% related in NonNeuroCBP. The DLFPC activates during acute pain and seems to have an inhibitory effect thereby minimizing the amount of pain perceived. Specifically, the DLFPC controls the orbitofrontal's function in negative pain perception. The thalamus is a major relay center of all sensory information, pain included. The anterior thalamus is a primary input of the anterior cingulate which, in chronic pain states, has shown decreased pain receptor (nociceptor) signaling. A decrease in signaling in the anterior cingulate would reduce the need for input from the anterior thalamus and could explain the atrophy seen there.

As this study was cross-sectional study and not a longitudinal study, the data can only establish relationships and not causality. However, the authors provide their explanation for the data collected -- the decreased density may be related to overuse atrophy in pain centers of the brain which undergo excitotoxicity and inflammation brought on by predisposing genetic or lifestyle factors.

One limitation, as discussed by the authors, is that the only means of truly confirming cellular atrophy is through a histological analysis which was not performed. The authors also noted their method of controlling for medicinal effects on brain tissue may not be sufficient to fully eliminate the impact on results. The study did not have enough subjects to warrant separating medicines into categories and relating those to brain morphometry, but future studies with larger sample sizes should use this method.

The authors provided clear data on the volume difference in the prefrontal cortex between groups but did not provide the same comparison of other areas. Supplemental material is available online through the Journal of Neuroscience, but does not contain clear tables with this data. This is a complex topic and a complex study, but the authors explain things simply and clearly without overly complicated descriptions. Individuals with greater knowledge on MRI usage and brain imaging may find more flaws than this review captures.

Why is this study important?

This study is important because it provides insight into additional deleterious effects of chronic pain. It would be interesting, as an expansion of this study to have each subjects individually treated by a movement specialist and monitor brain tissue atrophy throughout rehabilitation and beyond to note if atrophy continues, slows, stops or reverses.

How does it affect practice?

Clinicians should look beyond symptoms and attempt to identify the cause of low back pain, including the tissue in distress (muscle, joint, disc, fascia, nerve) and mechanical dysfunction (postural dysfunction) to ensure optimal care. Further, considerations of psychosocial issues and the effect on neurological factors contributing to pain should be included in assessment and treatment. An integrated approach with the intent of addressing all affected tissues and dysfunction may augment healing and alter afferentation. Further, the mechanical dysfunction should be evaluated via dynamic postural assessment (such as the Overhead Squat Assessment), and addressed with the same intent to alter all affected structures. Some of the techniques employed by the Brookbush Institute include - static and dynamic release techniques , joint mobilizations (as performed by a licensed professional or via self-mobilization), instrument assisted soft tissue mobilization (IASTM), and isolated and reactive activation techniques and integrated movement patterns , and kinesiology taping. This study reinforces the concept that the central nervous system (CNS) is the control center of movement and perception/response to sensation. Although the practice of human movement professionals is primarily mechanical, affecting the periphery, every professional should recognize that the end goal of all interventions is to positively alter CNS perception and control.

How does it relate to Brookbush Institute Content?

The Brookbush Institute identifies pain experienced in the lumbosacral region, with or without radiating symptoms, as a potential outcome of Lumbo Pelvic Hip Complex Dysfunction (LPHCD) and/or Sacroiliac Dysfunction (SIJ) . Both predictive models of dysfunction note imbalances involving the muscles that cross the lumbar spine, pelvis, and hip resulting in abnormal arthrokinematics, altered neurodynamics, and altered sensation. These alterations in motion, may result in tissue damage and pain. These models assist the practitioner in identifying commonly noted alterations in the human movement system as a foundation for intervention and further assessment.

The predictive model of LPHCD notes over-activity implying the use of release and lengthening techniques; in the lumbar extensors (Latissimus Dorsi , Erector Spinae , Multifidus , Rotatores, Interspinalis, Intertransversarii ) , hip flexors (Psoas , Iliacus , Tensor Fascia Latae (TFL) , Rectus Femoris , Anterior Adductor Complex , Sartorious ) and hip internal rotators (TFL , Gluteus Minimus , Anterior Adductor Complex , Biceps Femoris ). Further the hip and spine may require mobilization techniques to return optimal arthrokinematics (hip and spine ). The following muscles are found to be long and under-active implying the use of activation techniques: Lumbar Flexors (Rectus Abdominis , External Obliques , Internal Obliques , Intrinsic Stabilization Subsystem ), Hip Extensors (Gluteus Maximus ), and Hip External Rotators (Piriformis , Gluteus Medius , Gluteus Maximus , Deep Rotators of the Hip ). Treatment of LPHCD may require consideration of core subsystem activity. Commonly, the Anterior Oblique Subsystem (AOS) and Posterior Oblique Subsystem (POS) are under-active and implicate the use of integrative exercise.

Following the Brookbush Institute's predictive models of dysfunction will assist the clinician in properly addressing lumbosacral movement impairment. Search the video library for videos covering the following techniques used in addressing LPHCD .

Lumbo Pelvic Hip Complex Self Administered Release Techniques:

  • TFL
  • Anterior Adductors
  • Rectus Femoris
  • Latissimus Dorsi

Self Administered Mobilization Techniques:

  • Hip joint
  • Lumbar spine

Static Stretching Techniques:

  • Kneeling Hip Flexor Stretch
  • Standing Adductor Stretch
  • Child's Pose (Latissimus Dorsi)
    • Note: The"Latissimus Dorsi," "Kneeling Hip Flexor," & "Standing Adductor," are the most commonly used for Lumbo Pelvic Hip Complex Dysfunction.
      • Use the "Piriformis" and "Adductor Magnus" stretch for an Asymmetrical Weight Shift and/or SI Joint Dysfunction

Lumbo Pelvic Hip Complex Activation Techniques:

  • Glute max isolated activation
  • Glute medius isolated activation

Core Integration Techniques:

  • TVA activation

Lumbo Pelvic Hip Complex Integration Techniques:

  • Single-leg touchdown
  • Squat and row


  1. Triki, M., Koubaa, A., Masmoudi, L., Fellmann, N., Tabka, Z., Libyan, J. (2015) Prevalence and risk factors of low back pain among undergraduate students of a sports and physical education institute in Tunisia. Libyan Journal of Medicine. 10:26802; 1-10
  2. Meucci, R.D., Fassa, A.G., Faria, N.M. (2015) Prevalence of chronic low back pain: systematic review. Revista de Saúde Pública. 49. 1-10

© 2015 Brent Brookbush

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