Low urinary 5-hydroxyindole acetic acid in fibromyalgia syndrome: Evidence in support of a serotonin-deficiency pathogenesis

Y. K. Kang, I. J. Russell, G. A. Vipraio, I. N. Acworth

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Objective: One theory regarding the pathogenesis of fibromyalgia syndrome [FMS] suggests that its symptoms may be perpetuated by low levels of serotonin [5HT] at critical interneural junctions. Objective evidence supporting the 5HT deficiency hypothesis in FMS include low serum tryptophan [TRP], low serum 5HT, low platelet 5HT, and low cerebrospinal fluid [CSF] 5- hydroxyindole acetic acid [5HIAA]. The purpose of this study was to determine whether people with FMS would exhibit a lower than normal rate of urinary excretion of 5HIAA. Methods: Primary FMS patients and healthy normal controls [HNC] were recruited after informed consent. All sedative hypnotic and analgesic medications were discontinued for a period of two weeks before clinical evaluation. A brief questionnaire assessed the status of subjective pain, tiredness, depression, and limitation of physical function. Pain thresholds were documented by digital palpation and by dolorimetry. Spinal fluid was analyzed by radioimmunoassay for substance P [SP]. The volumes of 24-hour urine collections were recorded and 5HIAA levels were measured by high performance liquid chromatography. Statistical analysis was accomplished by t-tests, chi square tests, and the Pearson correlation method. Results: Nineteen FMS and 19 HNC participated in the study. The FMS patients were older and more female predominant than the HNC but the groups were ethnically similar. Subjective pain, tiredness, depression, and physical limitation were all more severe among FMS. The tender point index was higher and the average pain threshold [APT] was lower in the FMS group. The average CSF SP was significantly elevated in FMS. The concentration of 5HIAA in 24-hour urine samples was significantly lower than normal while the rate of excretion over the entire 24 hours was marginally lower in the FMS group. The low total 24- hour urinary 5HIAA did not correlate with age, severity of pain, tenderness, depression or CSF SP in either diagnosis group. The expected correlation of total 24-hour 5HIAA with APT was observed in HNC but was not apparent among FMS. Conclusions: These findings support the 5HT deficiency hypothesis of pathogenesis for FMS, since the lower than normal urinary 5HIAA in FMS suggests a sub-normal total body turnover of 5HT in FMS. It is not clear why this difference in apparent turnover of 5HT in FMS would not be more directly associated with the characteristic symptoms of FMS. Further study is indicated to test the validity of these observations and to better understand the responsible mechanisms.

Original languageEnglish (US)
Pages (from-to)14-21
Number of pages8
JournalLyon Mediterranee Medical Medecine du Sud-Est
Issue number3-4
StatePublished - 1998


  • 5-Hydroxyindole acetic acid
  • Fibromyalgia
  • Pathogenesis
  • Serotonin
  • Substance P

ASJC Scopus subject areas

  • Medicine(all)


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