Cystatin C as a cerebrospinal fluid biomarker for pain in humans

Andrew J. Mannes, Brian M. Martin, Hsiu Ying T. Yang, Jason M. Keller, Stacy Lewin, Robert R. Gaiser, Michael J. Iadarola

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Through a process of subtraction cloning and differential hybridization, we previously identified several new genes whose expression was induced by peripheral inflammation. One of these coded for cystatin C, a secreted cysteine protease inhibitor in the cystatin superfamily. We hypothesized that, concurrent with increased expression in dorsal horn, increased secretion would elevate the cystatin C content in cerebrospinal fluid (CSF) during active pain states. Alterations were assessed by immunoassay and by surface enhanced laser desorption ionization (SELDI) mass spectrometry with either reverse phase or immobilized anti-cystatin C antibody surfaces using CSF from ten age-matched obstetrical patients at term. Five control subjects were scheduled for an elective caesarian section and were not in pain. Another five subjects were in labor for 8.9±1h and were in severe pain as assessed with a visual analog scale and the McGill short form questionnaire. The level of cystatin C as measured by immunoassay in the non-pain patients was 2.77±0.75μg/ml and in the pain patients 5.36±0.92μg/ml (P<0.02). The elevation occurred without significant change in total CSF protein or β-endorphin content. The cystatin C increase also was detectable by SELDI with either raw CSF or after antibody capture. These data are consistent with our previous animal study and the idea that persistent pain induces the synthesis and release of cystatin C in dorsal spinal cord, the surplus of which overflows into the CSF.

Original languageEnglish
Pages (from-to)251-256
Number of pages6
Issue number3
StatePublished - Apr 2003


  • Cerebrospinal fluid
  • Cystatin C
  • Labor
  • Mass spectrometry
  • Matrix-assisted laser desorption ionization time of flight
  • Proteomics
  • Subtraction cloning
  • Surface enhanced laser desorption ionization

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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