Evidence of alpha-N-acetyl β-endorphin in human cerebrospinal fluid

Alpha-N-acetyl-β-endorphin (Ac-β-EP) is a post-translational product of β-endorphin (β-EP) with no analgesic properties. Ac-β-EP is present in human fetal and adult pituitary gland and cross-reacts in all available β-EP assays. This study evaluates levels of Ac-β-EP in the cerebrospinal fluid (CSF) of 22 normal subjects and 15 chronic headache sufferers. Since dopamine may play a role in the acetylation process, homovanillic acid levels were also determined. After extraction and high performance liquid chromatographic (HPLC) fractionation of CSF, an immunoreactive Ac-β-EP peak was detected coeluting with reference peptide, Ac-β-EP was detectable in all but 5 normal subjects. In headache sufferers, Ac-β-EP levels were always detectable and their mean value was significantly higher than that of healthy subjects (11.6 ± 11.8 vs 3.9 ± 3.6 fmol/ml; P <0.01). Conversely, CSF β-endorphin (β-EP) concentrations were decreased in headache patients (9.8 ± 9.4 vs 15.7 ±9.7 fmol/ml; P <0.05), and as a consequence the β-EP/Ac-β-EP ration was also markedly reduced (P <0.005). No difference was observed for CSF homovanillic acid concentrations.These data demonstrate that HPLC coupled to radioimmunoassay allows the identification of low but significant amounts of Ac β-EP in human CSF. This compound represents a confounding factor when β-EP immunoreactivity is assessed by conventional methods. In headache sufferers, Ac-β-EP levels were higher than normal, whereas β-EP concentrations were lower. This finding may thus be evidence for a lability factor, possibly worsening pain susceptibility in chronic headache sufferers.