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APRIL 2008 magazine 8/7/08 2:13 pm Page 9 F I B RO MYA LG I A
RESEARCH REVIEW
JOANNA RAWLING
Given the growing interest in the role of stress in fibromyalgia researchers from Germany compared the functioning of the development, the principal focus of this month's articles will HPA axis in both female fibromyalgia and chronic pelvis pain be stress and anxiety. In the words of a recent review article
patients. Chronic pelvis pain consists of persistent or recurring from the Center for Research on Pain, McGill University lower abdominal, pelvis and/or back pain, and like FMS, is Canada, “Despite the numerous cerebral alterations, associated with a number of other symptoms, including fibromyalgia might not be a primary disorder of the brain but headache, fatigue, gastrointestinal disturbances, sleep may be a consequence of early life stress or prolonged or problems, depression and anxiety. Chronic pelvis pain further severe stress, affecting brain modulatory circuitry of pain and resembles FMS in that many studies have failed to find any emotions in genetically susceptible individuals.” physical source of the symptoms. The German researchersrecruited 17 female FMS patients, 18 chronic pelvis painpatients, and 24 healthy female controls for the study.
STRESS RESPONSE AXIS IMPAIRED IN
Volunteers were first subjected to a “stress test”, in which they FIBROMYALGIA PATIENTS
were required to prepare and give a speech in front of anaudience, and then made to sit an arithmetic test! The levels A large proportion of fibromyalgia syndrome (FMS) patients of stress hormones in blood and saliva samples from the report a worsening of their symptoms (a “flare-up”) during volunteers were measured at 15 minute time intervals before, periods of stress. A recent biochemical study has confirmed during, and after the stress test, in order to see how their HPA that FMS patients do in fact struggle to cope with stress. The axis responded to stress. Interestingly, the total level of body's stress response system, termed the hypothalamic- cortisol was reduced in FMS patients compared to chronic pituitary-adrenal axis (HPA axis), helps the body to remain pelvis pain patients or the healthy controls. Cortisol is a stable under conditions of physical or psychological stress.
hormone produced by the adrenal glands in response to The HPA axis actually describes the interactions between stress, and plays an important role in glucose metabolism, three different components of the body: the hypothalamus blood pressure regulation and the immune system. Similarly, and the pituitary gland, both located in the brain, and the levels of cortisol in the blood were reduced in FMS patients adrenal glands, located at the top of each kidney. In addition (but not in chronic pelvis pain patients or in healthy controls), to its role in stress control, the HPA axis regulates a number of following direct stimulation of the HPA axis by drug treatment.
other functions of the body, including digestion, the immune Therefore this study seems to indicate reduced system, mood, and energy usage. In response to changes in responsiveness of the adrenal glands specifically in FMS the environment, the hypothalamus and pituitary gland in the patients. FMS sufferers face a constant battle with chronic brain relay messages to the adrenal glands, which react by pain and stress, which may reduce the ability of their stress producing several crucial hormones (see diagram). For response system (the HPA axis) to appropriately respond to instance, if the “fight-or-flight” response is signalled by the the “saber tooth tiger” when it appears. Further studies of hypothalamus in response to stress, the adrenal glands are adrenal gland biochemistry are now vital to build up a full instructed to produce hormones such as adrenaline and picture of the impaired stress response in fibromyalgia. cortisol. Production of these “stress hormones” leads to anincrease in blood sugar, heart rate and blood flow to themuscles, resulting in a sudden burst of strength. Althoughthis “fight-or-flight” response was once vital for early man toescape from a saber tooth tiger, this system has become over-stimulated in our modern-day, stressful environments! It istherefore not surprising that dysfunction of the HPA axis hasbeen reported for many disorders associated with chronicstress, including chronic fatigue syndrome, gastrointestinaldisorders, chronic pelvis pain and fibromyalgia. However,while a number of scientific studies have shown that the HPA axis is dysfunctional in fibromyalgia, there is considerableconfusion as to exact nature of this abnormality. For everystudy that suggests the adrenal glands are overactive, one can find another stating that they are underactive! In additionto individual differences between patients, (and related Wingenfeld, K., Heim, C., Schmidt, I., Wagner, D., Meinlschmidt, G., factors such as the drugs they were taking, menstrual cycle Hellhammer, D.H. 2008. “HPA axis reactivity and lymphocyte phase etc.), the widely differing results may simply reflect the glucocorticoid sensitivity in fibromyalgia syndrome and chronic different tests used by different laboratories to measure pelvic pain.” Psychosom Med. 70, 65-72. Department of Psychobiology, University of Trier, Trier, Germany.
In order to shed some light on this perplexing topic, APRIL 2008 magazine 8/7/08 2:13 pm Page 8 COPING STRATEGIES IN FIBROMYALGIA
anxiety (45%), compared to depression (31%), among FMSpatients. Anxiety disorders have previously been neglected in AND THE EFFECT OF POST-TRAUMATIC
chronic pain studies, however there is growing awareness of the STRESS DISORDER.
strong link between anxiety and chronic pain, and furtherattention should be given to the effect of anxiety on FMS. A Post-traumatic stress disorder (PTSD) is a chronic disorder that quarter of patients reported pain relief following improvements in follows a major stressful or traumatic experience such as an anxiety or depression, which the researchers suggest may be injury, assault, rape or warfare. Sufferers of PTSD re-experience indirectly linked. However the majority (75%), experienced pain the traumatic event and display an exaggerated response to relief with no accompanying change in anxiety or mood reminders of the initial trauma. In common with fibromyalgia symptoms. Although the mechanism of action of pregabalin in syndrome (FMS), PTSD patients also describe disturbed sleep and humans is currently unknown, studies in animals suggest that anxiety. There is a strong association between FMS and PTSD, pregabalin acts by dampening down the response of over-excited since the prevalence of PTSD is significantly higher among FMS nerve cells, reducing the release of chemicals responsible for patients than in the general population. Post-traumatic stress transmitting pain signals (neurotransmitters). It is hoped that disorder and fibromyalgia further overlap, as FMS is frequently licensing of the first drug for FMS will encourage further research triggered by a physical or emotional trauma. Researchers from into how pregabalin works, and improve our understanding of Israel proposed that the ability of individuals to cope with a exactly why FMS sufferers experience a low pain threshold. severe psychological trauma may affect the development of FMS.
1. Crofford, L.J., Rowbotham, M.C., Mease, P.J., Russell, I.J., Dworkin, R.H., Corbin, A total of 77 FMS sufferers, a proportion of whom also had PTSD, A.E., Young, J.P. Jr, LaMoreaux, L.K., Martin, S.A., Sharma, U. ; Pregabalin 1008- were questioned regarding previous traumatic experiences, and 105 Study Group, 2005. “Pregabalin for the treatment of fibromyalgia compared with 48 healthy controls. Volunteers were asked to syndrome: results of a randomized, double-blind, placebo-controlled trial.” describe their “coping styles”. “Coping” (the processes by which the individuals attempted to manage their emotions), was 2. Arnold, L.M., Crofford, L.J., Martin, S.A., Young, J.P. and Sharma, U., 2007. “TheEffect of Anxiety and Depression on Improvements in Pain in a Randomized, divided into “active” or “avoidant” coping. In active coping, the Controlled Trial of Pregabalin for Treatment of Fibromyalgia.” Pain Med 8, 633- individual attempts to alter the stressful situation, or their reaction to it, whereas in avoidant coping the individual distances Women's Health Research Program, Department of Psychiatry, University of him/herself from the stressful situation. The results, published in Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Rheumatology International, demonstrated that FMS patientswere more likely to use avoidant coping strategies compared withthe healthy controls. Interestingly, FMS patients that also suffered GROWTH HORMONE TREATMENT FOR
from post-traumatic stress disorder were more likely to suppress FIBROMYALGIA.
emotions, (avoided thinking about unpleasant events), than FMSpatients without PTSD. Suppression as a coping style has It has previously been suggested that a proportion of previously been associated with increased pain, thus it is possible fibromyalgia syndrome (FMS) patients have a deficiency of that the way a person perceives and responds to stress growth hormone. Growth hormone is produced by the pituitary influences FMS development. Alternatively, living with chronic gland situated in the brain (see previous diagram), and stimulates pain may hinder the ability of FMS patients to cope with stress the liver to produce a chemical known as “insulin-like growth and trauma. Either way, these recent findings suggest that factor 1” (IGF-1). IGF-1 is important for regulating the growth and therapies aimed at enhancing coping skills and managing stress development of cells in our body, and has a particularly important may be beneficial for fibromyalgia sufferers. role in the growth of nerve cells. Researchers from Barcelonathus decided to analyse the effect of growth hormone drug Ablin, J.N., Cohen, H., Neumann, L., Kaplan, Z. and Buskila, D., 2007.
“Coping styles in fibromyalgia: effect of co-morbid posttraumatic stress treatment in a group of 24 female patients with both severe FMS disorder.” Rheumatol Int. (E.pub ahead of print).
(16 or more tender points), and abnormal blood insulin-like Institute of Rheumatology, Tel-Aviv Sourasky Medical Center and Sackler growth factor levels. The FMS patients were randomly split into Faculty of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv, 64239, two groups: treatment group 1, treated with growth hormone in addition to three standard FMS drugs (amitriptyline, fluoxetine THE EFFECT OF PREGABALIN (LYRICA) ON
and tramadol), and treatment group 2, treated with the threestandard FMS drugs only. Patients were assessed at 3, 6, and 12 DEPRESSION AND ANXIETY.
months following the start of treatment, and the average numberof tender points, severity of FMS symptoms and quality of life Few significant advances have been made therapeutically for determined by questionnaires. The findings, reported in the BMC fibromyalgia syndrome (FMS), and indeed the best current Musculoskeletal Disorders journal, revealed that patients treatment for FMS is multidisciplinary, combining exercise and receiving the growth hormone treatment demonstrated an lifestyle changes. However a milestone was passed in 2007, with improvement in all aspects measured. Compared to the control the licensing by the US Food and Drug Administration of the first group 2, the average number of tender points per patient drug treatment for fibromyalgia, Lyrica or pregabalin (see last decreased by 60% in the growth hormone-treated group 1.
month's front cover of FaMily). Although Lyrica was originally However, the ability of growth hormone to improve FMS designed for treatment of neuropathic pain (pain from damaged symptoms over standard drug therapy treatment requires further nerves), the pharmaceutical company Pfizer recently completed research. The authors do not suggest exactly how growth clinical trials in adult FMS patients, demonstrating that Lyrica also hormone treatment acts to reduce pain levels in fibromyalgia reduces fibromyalgia pain. A team of researchers from the US patients, and it is also not known whether growth hormone could confirmed these findings, demonstrating that 450mg effectively treat FMS symptoms if taken alone, without the other pregabalin/day significantly reduced pain severity compared to a placebo drug (1). This group recently published a follow-up study in the Pain Medicine journal, which aimed to analyse the Cuatrecasas, G., Riudavets, C., Guell, M.A. and Nadal, A., 2007. “Growthhormone as concomitant treatment in severe fibromyalgia associated with potential impact of anxiety and depression on the response of low IGF-1 serum levels. A pilot study.” BMC Musculoskelet Disord 8, 119.
529 fibromyalgia patients to pregabalin treatment (2).
Servicio de Endocrinologia y Nutricion, Centro Medico Teknon, Vilana 12, E- Questionnaires revealed a higher incidence of moderate to severe

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