Is fibromyalgia an autoimmune disorder of endogenous vasoactive neuropeptides?☆
Introduction
Fibromyalgia (FM) is a disorder characterised by soft tissue pain, disturbance of function, an often prolonged course and variable fatigue and debility. A clearly defined aetiology and pathophysiology has not been described for this condition [1] and treatment types do not appear to significantly influence pain outcomes [2]. Recent detection of proinflammatory cytokines in skin tissues of patients with FM indicates neurogenic inflammation association with pain [3]. However the aetiology of these inflammatory findings remains unexplained.
The purpose of this paper is to propose a theoretical mechanism to explain the patho-physiology of FM. This paper proposes that immunological aberration is likely and this may prove to be associated with an expanding group of recently discovered vasoactive neuropeptides.
This paper examines some of the roles of endogenous vasoactive neuropeptides and explores possible mechanisms for their role in FM. While a possible autoimmune association between these relatively recently discovered neuropeptides and FM has not yet been confirmed in the literature [4], [5], this paper attempts to establish preliminary plausible links for further research.
Section snippets
Fibromyalgia, nociception and autoimmunity
Fibromyalgia is defined as the presence of both chronic widespread pain (CWP) and the finding of 11/18 tender points on examination [6]. FM pain cannot be explained on the basis of inflammation and altered musculoskeletal anatomy [7]. Hence pain mediation is asserted to be centrally mediated in FM, despite demonstrated lack of thalamic activity in FM patients, because of the lack of convincing peripheral pain mediation mechanisms [8].
Impairment of endogenous opioid function has been implicated
Vasoactive neuropeptides in fibromyalgia
Endogenous vasoactive neuropeptides exert many immunological functions and have a critical role in homeostasis of the immune system through different receptors expressed in a wide range of tissues [25]. Disturbances in their function are recognised as potential causes of autoimmune disease [26]. Failure of action of these neuropeptides may result through under-production, antibody neutralisation or interference with appropriate cell membrane binding sites and transmembrane conduction.
Vasoactive
Adenylate metabolism in fibromyalgia
Fatigue, amongst other causes, implies impairment of energy mediating mechanisms of mitochondria and purine metabolism within cells including secondary messenger functions of cAMP and cGMP. PACAP itself is responsible for adenylate cyclase activation in target tissues. Cyclic GMP is the G-protein associated transmembrane agent responsible for transmitter functions of many neuropeptides. These functions are mediated by purine nucleotides and adenosine.
Adenosine receptors mediate cytokines [48].
Conclusion and future directions
The vasoactive neuropeptides are proving to be an important group of substances acting at central and peripheral levels, exerting major influences on homeostasis through both the HPA and local sites of action.
Detection of anti-vasoactive neuropeptide antibodies, or antibodies directed to conduction mechanisms such as their respective G-protein receptor binding sites, might provide diagnostic tests for fibromyalgic disorders. The development of appropriate laboratory tests based on a valid
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The author declares no grants or financial conflict of interest are relevant in the development of this paper. Abstracts from PubMed, National Library of Medicine, were used in the development of this paper.