Neural correlates of clinical pain processing in neuropathic and inflammatory pain patients and comparison with experimental pain
The goal of this thesis was to examine the processing of clinical pain in two patient groups with well defined primary pathologies, i.e. neuropathic pain patients and patients with rheumatoid arthritis (RA). It was hypothesized that chronic pain is associated with plastic changes in pain processing brain structures that can be detected using functional magnetic resonance imaging (FMRI). The first study, presented in Chapter 3, demonstrates that the neural representation of experimental heat pain is different in neuropathic pain patients than in age- and gender-matched healthy control subjects, although the pain stimulus was applied outside clinically affected areas. Increased activation was found in amygdala and anterior insula in the patient group and was accompanied by increased state anxiety and depression scores. Anterior insula is the focus of Chapter 4 in which it is demonstrated that clinical pain processing is located significantly more anteriorly in the insula than experimental pain processing, in close proximity to neural correlates of highly negative emotions and the conscious perception of bodily sensations. This offers a potential explanation for the shift of clinical pain processing. In Chapter 5, clinical pain is contrasted with experimental pain in the same patient population, i.e. patients with RA. In addition to comparing clinical and experimental pain processing, it was investigated if emotional and cognitive determinates of the pain experience, specifically depression and catastrophizing, exert different influences on the two types of pain. It is shown that clinical pain, but not experimental pain, is likely to be driven partially by depressive symptoms whereas catastrophizing is associated with the same neural activation pattern in both conditions. The cerebral representation of allodynic pain in neuropathic pain patients is presented Chapter 6. Chapters 6 and 7 demonstrate that the FMRI signal encodes the perceived intensity of clinical allodynic pain across subjects and that it reflects longitudinal variations of the perceived intensity within subjects. This thesis illustrates that FMRI can reveal subtle differences in the processing of clinical and experimental pain, despite brain activation patterns being similar on the whole. It also indicates that FMRI can be used to elucidate the origin of these differences, for instance by studying the influence of emotional and cognitive variables. This suggests that neuroimaging methods, in particular FMRI, have the potential to dissect clinical pain into its constituent parts, including central sensitization, brainstem facilitation and amplification by psychological factors. Such knowledge could potentially be exploited to target treatment selectively at different components of clinical pain and to monitor longitudinal changes of these components separately.