EVIDENCE OF ALPHA-N-ACETYL BETA-ENDORPHIN IN HUMAN CEREBROSPINAL-FLUID

Alpha-N-acetyl-beta-endorphin (Ac-beta-EP) is a post-translational product of beta-endorphin (beta-EP) with no analgesic properties. Ac beta-EP is present in human fetal and adult pituitary gland and cross-reacts in all available beta-EP assays. This study evaluates levels of Ac-beta-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-beta-EP peak was detected coeluting with reference peptide. Ac-beta-EP was detectable in all but 5 normal subjects. In headache sufferers, Ac-beta-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 beta-endorphin (beta-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 beta-EP/Ac-beta-EP ratio 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 beta-EP in human CSF. This compound represents a confounding factor when beta-EP immunoreactivity is assessed by conventional methods. In headache sufferers, Ac-beta-EP levels were higher than normal, whereas beta-EP concentrations were lower. This finding may thus be evidence for a lability factor, possibly worsening pain susceptibility in chronic headache sufferers.