Chronic chlorimipramine does not reverse the reduction of cerebrospinal fluid Met-enkephalin-like immunoreactivity in chronic-pain patients.

Chronic-pain patients were treated for 10 days with chlorimipramine (100 mg i.v. daily), and their plasma levels of the drug and cerebrospinal fluid (CSF) levels of Met-enkephalin-like material (MELM) were measured for a comparison with those found in untreated chronic-pain patients and in control subjects. Pain relief in chlorimipramine-treated patients was apparently not associated with pronounced changes in the activity of enkephalinergic systems since the mean CSF levels of MELM were reduced to the same extent in treated (-49%) and untreated (-45%) pain patients as compared with controls. However, subtle chlorimipramine-induced alterations likely occurred as revealed by the simultaneous measurement of the CSF levels of 5-hydroxyindoleacetic acid (5-HIAA) in the same patients. Indeed, a positive correlation (r = 0.667) was found between CSF 5-HIAA and MELM levels in control subjects, whereas a negative correlation (r = 0.691) between these two parameters was detected in chlorimipramine-treated patients. These data suggest that chlorimipramine alters probable functional serotonin-enkephalin interactions in pain patients.