Chronic, unexplained pain

Chronic, unexplained pain (CUP) is a common clinical problem. The core symptom in this heterogeneous group of patients is pain for which no medical explanation is found. Patients also have many other characteristics (symptoms and psychosocial features) in common. Pathophysiologically, increased sensitivity for painful stimuli and abnormal pain processing in the brain seem to be of importance, but the empirical evidence for these mechanisms is limited. Part 1 of this thesis focused on epidemiological aspects of CUP. It is a common diagnosis in the Neurology outpatient clinic (15% of all new patients). At follow-up, the diagnosis is rarely revised to an 'explained' form of pain. In a cohort study in 422 CUP-patients, we found that several psychological factors are associated with pain severity and quality of life. However, the prognostic value of these factors for the clinical course of patients was poor. The second part of this thesis focused on pathophysiology. In a quantitative sensory testing study, we found that CUP-patients display increased sensitivity to several types of pain, but their sensitivity for non-painful heat and cold was decreased. CUP-patients were less susceptible to distraction from pain: the decrease in pain scores that is usually found in healthy subjects during distraction was not found in CUP-patients. Functional MRI revealed that the cerebral processing of pain in CUP during distraction is associated with abnormally high brain activity in pain registration areas (posterior insula), but low activity in pain modulatory regions such as the dorsolateral prefrontal cortex. In conclusion, the results in this thesis support the notion that CUP is a complex biopsychosocial problem, with a central role for abnormal, augmented pain processing in the central nervous system