M.Tech.

Indiana University-Purdue University Indianapolis (IUPUI) / Fibromyalgia (FMS) is a complex, chronic condition involving persistent and widespread pain of unknown origin. FMS is sometimes mistaken as psychiatric in origin; however, the precise origin and cause of FMS is unknown (Klippel et al., 1998). Worldwide prevalence rates range from 0.18-12%, with 0.18% in the United Kingdom (UK) (Hughes et al., 2006), 2% in the United States (US) (Wolfe et al., 1997), and 12% in Spain (Carmona et al., 2001). In the UK, there is debate over the existence of FMS (Bohr, 1995), and the reluctance of a general practitioner (GP) to diagnose conditions that are poorly defined (Hughes et al., 2006). Primary symptoms of FMS include generalized muscular pain, multiple tender points, sleep disruption and excessive fatigue. Additional symptoms include headaches, memory and concentration problems, dizziness, numbness/tingling, itching, fluid retention, abdominal cramps or pelvic pain and diarrhea (Hudson et al., 1992). Clearly, these symptoms may have an immense impact on daily life, limiting an individual’s functioning and emotional well-being. FMS is associated with significant societal and health care costs. Patients with FMS may repeatedly present to the general practitioner with various symptoms before a definitive diagnosis of FMS is made. As a result, general practitioners may be more likely to diagnose FMS in patients who frequently present with symptoms related to FMS, while patients who meet the diagnostic criteria but who rarely present at the practice may be missed (Ehrlich, 2003). The condition is of unknown etiology, and this, together with the lack of verifiable diagnostic criteria (i.e. lab tests), has led some to speculate that the disease does not or is at best a surrogate marker for underlying psychosocial problems. As such, the very process of diagnosing a patient with FMS may exacerbate symptoms and lead to increased dependence on health care providers (Ehrlich, 2003). This study examined the diagnoses of FMS made in “real-life” clinical practice and recorded by general practitioners in a large primary care population in the UK.

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Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Research objective To test a novel concept that exposing patients with fibromyalgia syndrome (FMS) to visuals of exercise activities elicits neurophysiological changes in functional brain areas associated with pain catastrophization; thereby providing preliminary support for the further development/testing of a virtual reality exposure therapy (VRET) exercise program aimed at reducing pain catastrophization toward exercise therapy in patients with FMS. Methods The main study of this research consisted of a three-phase exploratory fMRI study. Phase 1 involved the development/validation of the fMRI visual task. Phase 2 involved the exploration of the differences in neural correlates associated with pain catastrophizing between participants with FMS and healthy controls when exposed to various visuals of exercise and passive/relaxing activities. Phase 3 involved the testing of the preliminary efficacy of a novel VRET exercise program on pain catastrophization in participants with FMS. The fMRI task consisted of two stimuli: active (exercise activity visuals)/passive (relaxing activity visuals). Structural images as well as blood-oxygenation-level-dependent (BOLD) contrasts were acquired for the conditions and compared within-subjects/groups and between-groups. The condition of interest was the active>passive condition (where brain activations for the passive condition were subtracted from the active condition). The brain volumes collected during ‗on‘ conditions were compared with the brain volumes collected during ‗off‘ conditions using Students‘ t test. Statistic images were thresholded using clusters determined by Z>2.3 and a (corrected) cluster significance threshold of p=0.05. Results The right (R) middle and inferior frontal gyrus and R posterior cerebellum were significantly activated for the participants with FMS, and not the healthy control group, during the active>passive condition (phase 2). At baseline, during the active>passive condition (phase 3), the intervention/VRET group showed significant activation (p<0.05) in the R insular cortex, R anterior and posterior cerebellum, R parahippocampal gyrus, R middle frontal gyrus, R corpus callosum, R thalamus, R supramarginal gyrus and R middle and superior temporal gyrus; the control group showed significant activation in the R anterior and posterior cerebellum, R middle and superior temporal gyrus, R middle frontal gyrus, R insular cortex, R supramarginal gyrus and R precentral gyrus. Post-intervention, during the active>passive condition, R posterior cerebellum activation was still significant (p<0.05) for the intervention group; R anterior cerebellum, left (L) middle and inferior frontal gyrus, and R superior parietal lobe activation was found to be significant (p<0.000) for the control group, although these areas were not found to be significantly activated at baseline for the control group. Conclusion We could not provide confirmatory evidence for the efficacy of a novel VRET program for pain catastrophization in patients with FMS. However, the findings of this study does suggest that pain catastrophization in patients with FMS could be confirmed with fMRI. Research is therefore warranted to further develop a proper VRET exercise program and to test the effect of this program on pain catastrophization in patients with FMS. / AFRIKAANSE OPSOMMING: Navorsing doelstelling Om 'n nuwe konsep dat die blootstelling van pasiënte met fibromialgie sindroom (FMS) aan beeldmateriaal van oefening, ontlok neurofisiologiese veranderinge in funksionele brein-areas wat verband hou met pyn katastrofering te toets; sodoende voorlopige steun vir die verdere ontwikkeling/toetsing van 'n virtuele realiteit blootstelling terapie (VRET) oefenprogram wat gemik is op die vermindering van pyn katastrofering na oefenterapie in pasiënte met die FMS te bied. Metodes Die hoofstudie van hierdie navorsing bestaan uit 'n drie-fase verkennende fMRI studie. Fase 1 het die ontwikkeling/validering van die fMRI visuele taak behels. Fase 2 het die ondersoek van die verskille in die neurale korrelate geassosieer met pyn katastrofering tussen deelnemers met FMS en gesonde kontroles wanneer hulle blootgestel word aan verskeie beeldmateriaal van oefening en passiewe/ontspannende aktiwiteite behels. Fase 3 het die toets van die voorlopige effektiwiteit van 'n nuwe VRET oefenprogram op pyn katastrofering in deelnemers met FMS behels. Die fMRI taak het bestaan uit twee stimuli: aktiewe (oefening aktiwiteit beeldmateriaal)/passiewe (ontspannende aktiwiteit beeldmateriaal). Strukturele beelde sowel as bloed-suurstof-vlak-afhanklike (BSVA) kontraste is vir die toestande verkry en vergelyk binne-deelnemers/groepe en tussen-groepe. Die toestand van belang was die aktiewe>passiewe toestand (waar brein aktivering vir die passiewe toestand afgetrek is van die aktiewe toestand). Die brein volumes wat ingesamel tydens die 'aan' toestande is vergelyk met die brein volumes wat ingesamel is gedurende die 'af' toestande met die gebruik van Studente se t-toets. Drempel statistiek beelde is gegroepeer deur Z> 2,3 en 'n (gekorrigeerde) groepeerde betekenisvolle drempel van p = 0.05. Resultate Die regter (R) middel- en inferior-frontale gyrus en R posterior serebellum is betekenisvol geaktiveer vir die deelnemers met FMS, maar nie vir die gesonde kontrole groep nie, gedurende die aktiewe>passiewe toestand (fase 2). By basislyn, tydens die aktiewe>passiewe toestand (fase 3), die intervensie / VRET groep het betekenisvolle aktivering (p <0.05) in die R insulaire korteks, R anterior en posterior serebellum, R para- hippokampus gyrus, R middel-frontale gyrus, R korpus kallosum, R talamus, R supramarginale gyrus en R middel- en superior-temporale gyrus; die kontrole groep het betekenisvolle aktivering in die R anterior en posterior serebellum, R middel- en superior-temporale gyrus, R middel-frontale gyrus, R insulaire korteks, R supramarginale gyrus en R presentrale gyrus. Post-intervensie, tydens die aktiewe>passiewe toestand, was R posterior serebellum aktivering betekenisvol (p <0.05) vir die intervensie groep; R anterior serebellum, links (L) middel- en inferior-frontale gyrus en R superior pariëtale lob aktivering was betekenisvol (p <0.000) vir die kontrole groep, alhoewel geen betekenisvolle basislyn aktivering in hierdie areas by die kontrole groep plaasgevind het nie. Gevolgtrekking Ons kan nie bewyse vir die effektiwiteit van 'n nuwe VRET program vir pyn katastrofering in pasiënte met FMS bevestig nie. Nietemin, dui die bevindinge van hierdie studie wel daarop dat pyn katastrofering in pasiënte met FMS bevestig kon word met fMRI. Verdere navorsing is dus geregverdig om 'n behoorlike VRET oefenprogram te ontwikkel en die uitwerking van hierdie program op pyn katastrofering in pasiënte met FMS te toets.