Elevated Plasma Vasopressin and Normal Cerebrospinal Fluid Angiotensin-Converting Enzyme in Chronic Pain Disorder Kristian Wahlbeck, Markus Sundblom, Eija Kalso, Irma Tigerstedt, and Ranan Rim6n The study was performed proceeding from the hypothesis that pain proneness in chronic pain disorder ( CPD) is a result of alterations in central mechanisms regulating pain sensations. To elucidate the function of the central renin-angiotensin system, the levels of angiotensin- converting enzyme (ACE) and arginine vasopressin (A VP) in cerebrospinal fluid (CSF) and peripheral blood were measured in 15 CPD patients and 19 healthy controls. Plasma A VP levels (p = .01) as well as the serum osmolality (p = .01) were significantly higher in the CPD group. No significant differences in CSF ACE levels were found. AVP is a stress-related peptide, but central antinociceptive effects have also been reported. Elevated plasma A VP levels possibly may constitute a response to chronic stress. © 1996 Society of Biological Psychiatry Key Words: Pain disorder, angiotensin-converting enzyme, arginine vasopressin, cerebrospi- nal fluid, osmolality, cigarette smoking BIOL PSYCHIATRY 1996;40:994-999 Introduction Pain disorder is characterized by preoccupation with pain in the absence of any relevant organic pathology or pathophysiologic mechanisms. Psychological factors are judged to have an important role in the etiology of the disorder (American Psychiatric Association 1994). From the Department of Psychiatry (KW, RR) and Department of Anesthesiology (MS, EK, IT), University of Helsinki. Helsinki, Finland. Address reprint requests to Kristian Wahlbeck, MD. Department of Psychiatry, Lappviksvagen, FIN-00180 Helsinki, Finland. Received March 6, 1995; revised October 23, 1995. Although there are several biological similarities be- tween the chronic form of pain disorder (CPD) and depressive syndromes, e.g., low cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid and an increased frequency of serum cortisol nonsup- pression to dexamethasone (Almay 1987), the pathophys- iology of the CPD is still unresolved. The brain renin-angiotensin system (RAS) is a complex system of peptides regulating blood pressure and water homeostasis. The key enzyme in the RAS is angiotensin- converting enzyme (ACE, peptidyl-dipeptidase A, kini- nase II, E.C. 3.4.15.1), a dipeptidase with a broad substrate specificity. In the RAS, it converts angiotensin I into the © 1996 Society of Biological Psychiatry. 0006-3223/96/$15.00 SSDI 0006-3223(95)00577-3