Increased cerebrospinal fluid Met-enkephalin immunoreactivity in patients with chronic tension-type headache

Cerebrospinal fluid (CSF) concentration of Met-enkephalin immunoreactivity (Met-enkephalin-ir) was determined by radioimmunoassay in 47 patients with chronic tension-type headache and in 47 headache-free control subjects. Thirty-nine of the controls were patients receiving spinal analgesia before surgery for diseases not associated with pain; 8 were healthy paid volunteers. Patients reporting migraine more than 1 day per month were excluded. Pericranial tenderness, nociceptive flexion reflex and thermal pain thresholds were determined in the majority of the patients. The median level of CSF Met-enkephalin-ir was significantly higher (115 pmol/l) (quartiles (107-134) pmol/l) in the headache patients than in the controls (median 79 pmol/l) (quartiles (73-87) pmol/l) (Mann-Whitney, P < 0.001). No indication of sex-difference or correlation with age with respect to CSF Met-enkephalin-ir was found. No correlation was found between CSF Met-enkephalin-ir and either pericranial tenderness, nociceptive flexion-reflex threshold, or thermal pain threshold. There was no indication of correlation between consumption of mild analgesics and CSF Met-enkephalin-ir. The higher levels of CSF Met-enkephalin-ir in the headache patients may be indicate activation of the enkephalinergic antinociceptive system at the spinal/trigeminal level, whereas the beta-endorphinergic system appears normal. This enkephalinergic activation may be caused by increased activity in the primary nociceptive afferents, or may be compensatory to decreased activity in other endogenous antinociceptive systems than the opioid.