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An Evolutionary Stress-Response Hypothesis for Chronic widespread Pain (Fibromyalgia Syndrome)

Pamela Lyon PhD, Milton Cohen, MD FFPMANZCA and John Quintner MB FFPMANZCA


By Bianca Monterosso


Fibromyalgia tends to be defined as a frustrating condition in primary health care.  Many patients present with symptoms of Fibromyalgia, however considering the lack of pathological understanding and limitations in diagnostic testing, it can often lead patients down a negative psychosocial path.

Lyon have structured this paper to merge two themes regarding chronic widespread pain (Fibromyalgia Syndrome).  It is hypothesised that FS is a direct resultant of central sensitization of nociception and also has a link to the activation of a global stress response.  This merge of concepts particularly targeted to Fibromyalgia Syndrome really draws down into the fundamental cause of this stereotypically controversial condition.  While there are still many limitations in the understanding of central sensitisation of nociception, a very promising recognition of a neuropeptide namely substance P has been show to be a biochemical indicator of Fibromyalgia, with proof of its role in development of central nociceptive sensitisation. 

Substance P, also referred as the “pain tramsmitter” (Lyon is released and/or activation of its receptor NK1R, appears to be related to stress responses with strong links to the Central Nervous System mostly associated with the hypothalamic-pituitary-adrenal axis.  The HPA axis is typically regarded as the primary “stress” circuit of the body and an interface between brain and the immune system. 

As Substance P is renowned as a modulator of nociception with it’s involvement of signalling the intensity of noxious stimuli, its overactivity or overproduction can induce an unresolved stress response accounting for the varied symptoms presenting along with chronic pain. The diversity of symptoms for Fibromyalgia patients can also be attributed to Substance P’s close link with this particular stress response, initiating many complaints from cognitive difficulty to gastrointestinal issues such as IBS. Cortisol, a stress hormone is a result of the stimulation of the HPA axis which in high levels can prove to impact on a patient in many ways, showing the complexity and variability of symptoms seen in FM patients.


Interestingly enough as Lyon points out, SP concentrations can be induced and increased both from psychological stimuli such as Post Traumatic Stress Disorder as well as physical stimuli like chronic pain.  This unique correlation does not specifically mean that psychological stress is necessarily a causative factor of FM, but to simply show that psychological and physiological stress response is in fact associated closely with elevated SP. This can therefore be attributed to the hypothesis that FM along with PTSD are manifestations of a hyperactive stress response; differences in clinical presentation may indeed reflect variability of genotypic and phenotypic traits catering towards the varied presentations seen in both physiological and psychological patients.

The hope now discussed with Lyon is to define a less invasive way of measuring for Substance P levels to be a reliable biomarker for chronic activation of the stress response. This hypothesis shows potential promise in the explanation and mechanism behind generalised widespread pain. It also provides new hope in diagnostic tools and to assist in the eradication of stigma associated with Fibromyalgia in the primary health care setting.  


As an FM sufferer, this paper and the hypothesis discussed sheds some much needed light on a pathological link to Fibromyalgia Syndrome.  It opens the doors to a much more positive future in the adaptation of research and treatment techniques and in turn, has the capability to improve the quality of life for many FM sufferers.

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