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Detection of Interleukin 1ß (IL-1ß), IL-6, and Tumor Necrosis Factor-a in Skin of Patients with Fibromyalgia
SOUZAN SALEMI, JANINE RETHAGE, UWE WOLLINA, BEAT A. MICHEL, RENATE E. GAY, STEFFEN GAY, and HAIKO SPROTT

ABSTRACT.

Objective. To determine if abnormal collagen metabolism is correlated with neurogenic inflammation, a potential activator of collagen metabolism, in patients with fibromyalgia (FM).Methods. The presence of inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-a was investigated in skin tissues by using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Fifty-three skin biopsies from female patients with FM (30-65 years of age) were examined and compared to skin biopsies of 10 age and sex matched healthy controls. Biopsies were obtained from the left deltoid region. Rheumatoid arthritis synovial fibroblasts and tissues were used as positive controls for the expression of cytokines. Total RNA isolated from the tissue samples were reverse transcribed (RT) by random hexamers as the primer for RT followed by PCR amplification using specific primers for IL-1ß, IL-6 or TNF-a. Expression of IL-1ß, and TNF-a protein was investigated in the skin by immunohistochemistry using specific antibodies (avidin-biotin method).

Results. Positive sig.

Conclusion. The detection of cytokines in FM skin indicates the presence of inflammatory foci (neurogenic inflammation) in the skin of certain patients (about 30% of FM patients), suggesting an inflammatory component in the induction of pain. This may explain the response to nonsteroidal antiinflammatory therapy in a subset of FM patients. (J Rheumatol 2003;30:146-50)

nals (RT-PCR) were detected in skin tissues of 19/50 (38%) FM patients for IL-1ß, in 14/51 FM patients (27%) for IL-6, and in 17/53 patients (32%) for TNF-a. None of the cytokines could be detected in healthy control skin. Immunoreactivity for IL-1ß and TNF-a was demonstrated in certain skin tissues of our FM patients

What is fibromyalgia (FM)?

Fibromyalgia (pronounced Fie-bro-my-AL-ja) is a complex chronic pain illness that challenges patients and healthcare professionals alike. FM experts estimate that about 10 million Americans suffer with FM. While it is most common in women, FM also strikes men and children of all ages and ethnic backgrounds worldwide. For those with severe symptoms, FM can be extremely debilitating and interfere with routine daily activities.

What are the symptoms?

PAIN -The pain of FM is profound, widespread and chronic. It knows no boundaries, affecting any or all parts of the body with varying intensity. FM pain has been described as deepmuscular aching that can throb, stab, tingle or burn. A variety of factors such as weather changes, stress and activity level can affect the nature and severity of the pain.

FATIGUE - The fatigue of FM is an all-encompassing exhaustion that interferes with even the simplest daily activities. It can feel like every drop of energy has been drained from the body, leaving the individual with a limited ability to function both mentally and physically.

SLEEP PROBLEMS - Research has documented distinct abnormalities that frequently occur at various stages of sleep in people with FM. The result is non-restorative sleep thatcan amplify symptoms.

OTHER SYMPTOMS - People with FM often report "brain fog," characterized by problems with cognitive functioning, memory and concentration. Other common complaints include irritable bowel, headaches and migraines, chemical or environmental sensitivities, restless legs, and neurological symptoms such as dizziness, vision problems, numbness, tingling or impaired coordination.

How is FM diagnosed?

Since people with FM tend to look healthy and conventionaltests are typically normal, a physician knowledgeable about the illness is necessary to make a diagnosis. In 1990, the American College of Rheumatology (ACR) established official diagnostic criteria for fibromyalgia, which includes:

A history of widespread pain in all four quadrants of the body for a minimum duration of three months.

Pain in at least 11 of 18 designated tender points when a specified amount of pressure is applied.

What causes FM?

Previously thought to be primarily a musculoskeletal disorder, recent research provides evidence that FM is actually a problem resulting from disordered sensory processing in the central nervous system. Due to hormonal and chemical abnormalities, the individual experiences central sensitization which leads to pain amplification. Studies have found major abnormalities in the levels of various neurochemicals in the brain, such as serotonin, substance P and nerve growth factor. Brain-imaging techniques also reveal an abnormal decrease in blood flow to specific areas of the brain.

Fibromyalgia often occurs following a physical trauma - such as an acute illness or injury - which may act as a "trigger" in the development of the disorder. Emerging evidence also suggests a genetic component which may cause some individuals to be more susceptible to the disorder. With interest in FM research at an all-time high, scientists will continue to untangle the truths about this complex illness.

How is FM treated?

Since there is no known "cure" for FM, treatment focuseson relieving symptoms and improving function. Successful FM treatment requires a multidisciplinary approach that addresses the wide-ranging effects the illness has on the individual's life. It is important for the person with FM to develop an individualized self-management plan. A variety of health care professionals, family and friends can take an active role in supporting the self-management program to ensure a team approach to better health.

MEDICATIONS: A variety of drug therapies are often used to reduce pain levels and improve sleep. Over-the-counterpain relievers such as ibuprofen and acetaminophen may help patients relieve mild pain. The physician may prescribe low doses of tricyclic antidepressants, muscle relaxants, sleep medications, selective serotonin reuptake inhibitors, COX-2 inhibitors or one of the new non-narcotic prescription pain relievers. Stronger narcotics may be necessary for occasional flare-ups or for individuals who do not respond to other treatments. Local anesthetic or corticosteroid injections may be appropriate for those with severe tender point pain. A variety of other medications are often prescribed to relieve overlapping conditions, such as irritable bowel and restless legs syndrome.

OTHER THERAPIES: Physical therapy, application of heat or cold, massage, myofascial release, acupuncture andchiropractic manipulation are a few therapies that have been beneficial for some individuals. A program of gentle, graded exercise has been found to reduce pain and stiffness as well as maintain muscle and cardiovascular strength. Relaxation exercises and breathing techniques can help decrease pain and anxiety. Counseling, support groups, cognitive therapy and biofeedback can be beneficial in helping people with FM and their families cope with the emotional challenges faced by a person with chronic pain.

LIFESTYLE CHANGES: One of the most important factors in successfully managing FM is recognizing the need for lifestyle adaptation. Increasing rest, pacing activities carefully, reducing stress, practicing relaxation techniques and improving nutrition can all be useful strategies to minimize symptoms and improve quality of life.

What is the prognosis?

The prognosis is promising. Better ways to diagnose and treat FM are on the horizon. Increased information and awareness are helping to improve the quality of life for people with FM. By actively seeking new information, re-evaluating daily priorities, making lifestyle changes, and working hard to keep a hopeful attitude, people can live well with fibromyalgia!

5-HTP can help increase the tolerance of pain and PARACTIN has been proven to reduce pro-inflammatory cytokines such as TNF.

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