Brain chemistry reflects dual states of pain and anxiety in chronic low back pain

I. D. Grachev*, B. E. Fredrickson, A. V. Apkarian

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


The neurobiology of the interaction between pain and anxiety is unknown. The present study examined interrelationships between: regional brain chemistry (as identified by in vivo proton magnetic resonance spectroscopy [1H-MRS] in dorsolateral prefrontal cortex [DLPFC], orbitofrontal cortex [OFC], cingulate and thalamus), pain (as measured by short form of the McGill Pain Questionnaire [SF-MPQ]), and anxiety (measured by the State-Trait Anxiety Inventory) in chronic low back pain (CLBP) patients, and contrasted to the relationship between brain chemistry and anxiety in sex and age-matched normal subjects. The results show that brain chemistry depends on a 3-way interaction of brain regions examined, subject groups (normal vs. CLBP), and anxiety levels (high vs. low). The concentration of N-Acetyl aspartate (the largest peak in 1H-MRS) in OFC could distinguish between anxiety levels and between subject groups. Chemical-perceptual relationships were analyzed by calculating correlations between regional chemicals and perceptual measures of pain and anxiety. To isolate pain from anxiety, these maps were subdivided based on anxiety and, in the CLBP patients along anxiety-more-related vs. anxiety-less-related pain descriptors and along sensory vs. affective pain descriptors. There was a precise relationship between perception and brain chemistry. The chemical-perceptual network best related to pain in CLBP patients was comprised of the DLPFC and OFC; the chemical-anxiety network was best related to the OFC chemistry in normals and to all four regions studied in CLBP patients; and the cingulate was best related to the affective component of pain. We conclude that the chemical-perceptual mapping differentiates between closely related perceptual states of pain and anxiety in chronic pain and provides a brain regional-chemical-perceptual description of the long-term reorganization that occurs with chronic pain.

Original languageEnglish
Pages (from-to)1309-1334
Number of pages26
JournalJournal of Neural Transmission
Issue number10
StatePublished - 2002


  • Anxiety
  • Brain chemistry
  • Chronic low back pain
  • Neurotransmitters
  • Prefrontal cortex
  • Proton magnetic resonance spectroscopy.

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry


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