What are the roles of oxidative stress and pro-inflammatory cytokines in fibromyalgia?

FM is characterized by chronic widespread pain and painful body pressure points (tender points).

Several researchers suggest that elevated levels of the pronociceptive substance substance P enhance pain experience (sensitization of ascending pain pathways). FM is often accompanied by several non-specific symptoms including fatigue, stiffness, disordered sleep, cognitive dysfunction, dysesthesia, psychological distress, headaches, and poor balance. These non-specific symptoms are also observed in ‘sickness behavior’ which is induced by infectious and inflammatory processes, characterized by cytokines. A literary search for cytokines in FM patients suggested several upregulated cytokine levels in FM patients, compared with controls. Furthermore, diseases that show overlap with FM are characterized by enhanced oxidative stress levels. Another literary search regarding oxidative stress in FM patients suggested upregulated oxidative stress levels in FM patients, compared with controls. Eventually, this thesis hypothesized that oxidative stress might be responsible for increased substance P levels via cytokine generation, resulting in elevated pain experience. To place this hypothesis in a broad perspective, the physiological effect of several associated co-morbidities (e.g. diabetes) have been analyzed.

Because FM symptoms appear to be caused by elevated cytokine- and oxidative stress-levels, inhibition of cytokine- and oxidative stress- levels as treatment should be examined.

Oxidative stress inhibition treatment

Injections with vitamin B12, which scavenges nitric oxide, showed alleviations of symptoms in FM patients, CFS patients and multiple complex syndrome patients. Furthermore, intra-muscular GSH injections showed positive results after 6 months of treatment; 82% of the patients experienced improvement in fatigue, 71% showed improvement in memory and concentration, and 62% experienced improvement in levels of pain. Finally, the administration of N-acetyl-cysteine, a strong anti-oxidant that supports GSH homeostasis, delays muscle fatigue in exercising humans.

In summary, it appears that non-pharmaceutical- and pharmaceutical-treatments based on cytokine- and oxidative stress- inhibition, have clinical effect in diseases that show overlap with FM.

M.S.C.E. Vorage (author):  Clinical & Health Psychology, Utrecht, The Netherlands Master thesis of the University of Utrecht, the Netherlands

Master thesis Maurice VorageWhat are the roles of oxidative stress and pro- inflammatory cytokines in fibromyalgia?


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