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PAIN MEDICINE

Increased Systemic Catecholamines in Complex Regional Pain Syndrome and Relationship to Psychological Factors: A Pilot Study

R. Norman Harden, MD^*,,, Nathan J. Rudin, MA MD, Stephen Bruehl, PhD^||, William Kee, PhD^¶, Devang K. Parikh, MS^#, Jason Kooch, MD, Thomas Duc, MD^¶, and Richard H. Gracely, PhD^**

*Center for Pain Studies, Chicago, Illinois; Rehabilitation Institute of Chicago, Chicago, Illinois; Northwestern University Medical School, Chicago, Illinois; Department of Orthopedics and Rehabilitation Medicine and Pain Treatment and Research Center, University of Wisconsin Medical School, Madison, Wisconsin; ||Vanderbilt University School of Medicine, Nashville, Tennessee; ¶Medical University of South Carolina, Charleston, South Carolina; #University of Pennsylvania, Philadelphia, Pennsylvania; and **Chronic Pain and Fatigue Research Program, University of Michigan Health System, Ann Arbor, Michigan

Address correspondence and reprint requests to R. Norman Harden, MD, Rehabilitation Institute of Chicago, Center For Pain Studies, 446 E. Ontario, Ste. 1011, Chicago, IL 60611. Address e-mail to nharden{at}rehabchicago.org

We have demonstrated that subjects with complex regional pain syndrome (CRPS) have asymmetric venous pool plasma concentrations of norepinephrine (NE) when affected and unaffected limbs are compared, with most demonstrating decreased NE levels in the affected limb. This pilot study explored whether systemic venous plasma catecholamine levels in CRPS subjects with sympathetically maintained pain (SMP) differ from those found in healthy volunteers. We also explored whether catecholamine levels were correlated with scores on psychometric measures of depression, anxiety, and personality. Venous blood samples from 33 CRPS/SMP patients (from unaffected limbs) and 30 healthy control subjects were assayed for plasma NE and epinephrine (E) concentrations. Plasma NE levels were significantly higher in the CRPS group (P < 0.001). Statistical comparisons of E levels across groups did not achieve significance (P < 0.06), although 52% of CRPS/SMP patients had E levels exceeding the 95% confidence interval based on control data. Significant positive correlations were found between E levels and scores on the Beck Depression Inventory and Scales 1, 3, and 6 on the Minnesota Multiphasic Personality Inventory-2 (all P < 0.05). This preliminary work suggests that increased NE and E levels in CRPS/SMP patients may result from the pain of CRPS, consequent affective distress, or both. Alternatively, our findings could reflect premorbid adrenergic hyperactivity caused by affective, endocrine, or other pathology, which might predispose these individuals to develop the syndrome. Definitive studies are needed to examine these hypotheses in detail.

IMPLICATIONS: This pilot study explored systemic venous plasma catecholamine levels in complex regional pain syndrome and the correlation with scores on psychometric measures. Our results suggest that increased catecholamine levels may result from pain or may reflect premorbid adrenergic hyperactivity, which could predispose these individuals to develop the syndrome.

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