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Evaluation of sympathetic skin response and F wave in fibromyalgia syndrome patients / fibromiyalji sendromlu hastalarda sempatik deri yaniti ve F dalgasinin degerlendirilmesi.

Fibromyalgia syndrome (FMS) is a chronic disorder which is characterized by diffuse, widespread pain and the presence of tender points. (1) Various etiologies have been proposed for FMS, but the etiology and pathophysiologic mechanism for diffuse pain is still unknown.

It is possible that several phenomena may play overlapping roles in the development of the syndrome and one of these may be autonomic nervous system (ANS) dysfunction. (2) Pain is the major symptom, and recent studies have considered this to be neuropathic pain related to central nervous system sensitization. (3) Studies have also shown the association of this pain with sympathetic neurotransmitters and increased function in the sympathetic nervous system of FMS patients. (4-6) Stress response plays an important role in the symptoms, and it is believed that the ANS has a close relationship with the efficiency of the stress response and the hypothalamic-pituitary-adrenal axis (HPA). (7)

A simple and reliable neurophysiologic method to evaluate the ANS is the study of the sympathetic skin response (SSR). (8), (9) Using an electrical stimulation, the eccrine sweat glands of the skin are activated via a reflex loop which includes large, myelinated sensory fibers, central synapses and efferent sympathetic pre-and post-ganglionic nerve fibers. (9)

Fibromyalgia syndrome has complex symptoms and the role of the peripheral nervous system (PNS) in these is not yet clear. Only a few studies have described abnormal electrodiagnostic test results. (10) F wave is a late response recorded from the muscle elicited by an electric impulse conveyed antidromically to alpha-motor neurons in the spinal cord. F wave latency and frequency are assessed to provide information about the proximal segment conduction of the nerves. (11) In this study, F wave is investigated to determine whether the PNS has been affected in FMS.

This study was designed to investigate the electroneuromyographic (ENMG) evaluation of the SSR and F wave in FMS and their correlation with clinical outcomes.


The fibromyalgia syndrome group was recruited from the patients admitted to the Physical Medicine and Rehabilitation (PMR) outpatient clinic between March 2005 and March 2006 with widespread musculoskeletal pain. Among 68 patients, 38 (1 male, 37 females; mean age 40.6[+ or -]9.6 years; range 22 to 60 years) meeting the 1990 American College of Rheumatology classification criteria for FMS were enrolled in this study. The control group included 30 healthy volunteers (1 male, 29 females; mean age 39.5[+ or -]9.0; range 22 to 55 years). A total of 75 healthy subjects were screened over a one year period. Fifty subjects without musculoskeletal pain complaint and with no disabling coexisting diseases were eligible for the study. Most of them were accompanying persons of the patients. They were informed about the research, and 20 of them did not approve electrodiagnostics tests. Thirty healthy controls gave written consent and enrolled in this study. After a physical examination, routine laboratory investigations including full blood count, erythrocyte sedimentation rate (ESR) and biochemical markers were carried out. Exclusion criteria for this study were entrapment neuropathies-polyneuropathies (based on electrodiagnostic tests), malignancy, diabetes mellitus, chronic renal failure, and inflammatory joint disease. None of the patients was under medication such as tricylic antidepressants, muscle relaxants or analgesics for at least four weeks before therapy.

Clinical assessment

The number of tender points (NTP), pain, depression and functional capacity of the patients were evaluated. Tender points were determined by an algometer (Greenwich, USA). Pain was assessed using a 10 cm visual analog scale (VAS) where 0 corresponded to no pain and 10 to the worst pain. Functional capacity was evaluated by the fibromyalgia impact questionnaire (FIQ) which is a self-administered questionnaire consisting of 10 criteria, including physical function, work status, anxiety, pain, fatigue, sleep, depression, stiffness and well-being. It has different scores for each item and a final calculation was done on a maximum score of 100. (12) Beck's depression inventory (BDI) was used to evaluate the level of depression. It is also a self-administered questionnaire and consists of 21 items with a range of 0-63 where higher scores indicate major depression. (13)

Electrodiagnostic testing

After clinical examination, all patients were investigated in an ENMG laboratory by means of SSR and F wave. All electrodiagnostic tests were performed by using a Neuropack MEB-2200 Nihon Kohden ENMG apparatus at a room temperature of 26 [degrees] C. Before testing, and patients were informed about taking a restful sleep, stopping coffee and alcohol intake.

F wave studies were performed for median and ulnar nerves bilaterally. The active electrode was placed over the middle of the muscle belly of the abductor pollicis brevis for the median nerve and the abductor digiti minimi for the ulnar nerve. The reference electrodes were placed distally. F waves were recorded when the muscle relaxed. At least 20 supramaximal stimulations were applied in a random fashion, and mean F latencies were recorded from each of the extremities.

For measurement of the SSR, the same ENMG equipment was used. The skin temperature was maintained at 32[degrees]. Active surface electrodes were attached on the palmar side, and the references were placed on the dorsum of the hand. The stimulus was given at the wrist contralateral to the recording side. Measurements were taken from both arms. An intensity of 20-30 mA with an irregular interval of more than one minute was preferred to prevent habituation. When habituation occurred, stimulation was delayed for about three or four minutes. Skin potentials were recorded for a 10 second analysis period. The latency and peak to peak amplitude were determined. Mean values were used for each parameter. Sweep speed was 500 ms/div. Sympathetic skin response was considered absent if there was no response after 10 stimulis.

Informed consent was obtained before the examination and the local Ethical Committee of Kocatepe University granted approval for the study.

Statistical analysis

All parametric results were expressed as mean [+ or -] SD for each group. For the analysis of gender in a matched case control, Mantel-Haenszel odds ratio was used. Statistical analyses were performed using the student t-test to compare mean values of F wave distal latency and the amplitude and distal latency of SSR between the groups. Results were reported in 95% confidence intervals. The correlation between the clinical findings and electrodiagnostic tests was analyzed using the Spearman correlation. All analysis were performed using the SPSS (SPSS Inc., Chicago, Illinois, USA) 10.0 version for Windows software program.


All patients completed the study. No statistically significant difference was found in gender between the groups (odds ratio=1.27). Thirty-three patients in the FMS group and 27 patients in the control group were married. The clinical evaluation of the FMS patients and control group is shown in table 1.
Table 1. Demographic data and clinical evaluation of groups

                  Fibromyalgia                  Control     p
                     (n=38)                      (n=30)
                        n         Mean[+ or  n   Mean[+ or
                                  -]SD           -]SD

Age (years)                     40.6[+ or      39.5[+ or  0.707
                                    -]9.6          -]9.0


Female                      37             29             0.330

Male                         1              1             0.330

Disease duration            12

Visual analog                7

Beck depression             15

Fibromyalgia                63

Number of tender            14

SD: Standard deviation.

The results of the blood count and routine biochemical parameters were within normal ranges for both groups.

In the evaluation of SSR, in FMS patients we observed a statistically significant decrease in distal latency, and a statistically significant increase in amplitude, when compared with the control group (p < 0.05). However, no statistically significant difference was found in the distal latency of the F wave between the groups (p > 0.05). The results are shown in table 2.
Table 2. Electroneuromyographic evaluation of sympathetic skin
response and F wave of fibromyalgia syndrome patients and controls

                Fibromyalgia       Control          95%         P
                  syndrome         (n=30)        interval
               Mean[+ or -]SD     Mean[+ or

Right median   1.3[+ or -]0.3         1.5[+ or  0.36-0.08*  0.002
SSR latency                              -]0.2

Left median    1.3[+ or -]0.4         1.6[+ or  0.46-0.18*  0.000
SSR latency                              -]0.2

Right median   3.4[+ or -]1.9         2.2[+ or   0.37-2.0*  0.005
SSR amplitude                            -]1.4

Left median    3.2[+ or -]1.8         2.3[+ or   0.13-1.7*  0.023
SSR amplitude                            -]1.5

Right median        27.2[+ or        27.6[+ or    -1.5-0.7  0.909
F wave                  -]2.1            -]2.6
latency (ms)

Right ulnar F       26.5[+ or        25.5[+ or    -0.7-2.7  0.806
wave latency            -]2.2            -]4.7

Left median F       26.6[+ or        27.1[+ or    -1.6-0.6  0.751
wave latency            -]2.2            -]2.7

Left ulnar F        26.6[+ or  26.5[+ or -]2.3    -0.7-1.2  0.830
wave latency            -]1.9

SD: Standard deviation; *: Statistically significant level; SSR:
Sympathetic skin response.

There was no statistically significant correlation between the SSR amplitude and distal latency results and VAS, BDS, FIQ and NTP scores in the FMS group (p > 0.05). Also, no significant relationship was observed between F latency and clinical findings (p > 0.05; Table 3).
Table 3. Results of the correlation of electrodiagnosting tests
and clinical evaluation in fibromyalgia syndrome patients group

                             sydrome (n=38)
                     SSR     SSR (amplitude)  F wave
                  (latency)                     latency

Visual analog       r=0.182          p=0.288  r=0.218
                    p=0.202          r=0.058  p=0.738

Beck depression     r=0.053          p=0.757  r=0.069
                    p=0.690          r=0.308  p=0.067

Fibromyalgia        r=0.192          p=0.261  r=0.049
                    p=0.778          r=0.106  p=0.540

Number of tender    r=0.122          p=0.478  r=0.176
                    p=0.322          r=0.058  p=0.738

SSR: Sympathetic skin response; FMS: Fibromyalgia syndrome.


The main symptom of FMS is diffuse, chronic pain. Upon clinical examination, no obvious systemic illness is diagnosed. In addition, clinical neurological examination and electrodiagnostic tests including needle ENMG and nerve conduction velocities are normal in FMS. (14), (15)

Previous studies have investigated the role of autonomic nervous system dysfunction in FMS. The SSR which facilitates examination of the function of the autonomic nervous system simply, practically and effectively has been used extensively. Since the afferent and efferent pathways of the SSR are well known, it has been used in the clinical diagnosis of peripheral autonomic dysfunction for some cases. (16-18)

Most of these previously mentioned studies have shown that increased sympathetic nervous system activity, or enhanced responsiveness to sympathetic activity, enhances symptoms in patients with FMS. Some of these studies showed elevated function in the sympathetic nervous system. (4-7) Martinez-Lavin et al. (19) suggested that fibromyalgia patients have norepinephrine-evoked pain which may be resolved by sympatholytic maneuvers. They also proposed that sympathetic hyperactivity may explain some of the manifestations of FMS including sleep disorders, irritable bowel syndrome, sicca symptoms and anxiety. (20) Considering a hypothesis of alteration of muscle and tissue blood flow as well as participation of the sympathetic nervous system, Bennett et al. (21) have demonstrated excess Raynaud's-like symptoms and objective evidence of cold sensitivity in fibromyalgia. Twelve of 29 FMS patients had a decrease in finger systolic pressure of more than 20% after cooling. Additionally, Bengtsson and Bengtsson (22) have noted that regional sympathetic blocks improved the symptoms.

In our study, fibromyalgia patients had significantly higher amplitudes and lower latencies for both sides when compared with controls. In other words, increased SSR amplitude and decreased SSR latency support the hypothesis of sympathetic nervous system alteration in our FMS patients. Many studies have shown increased amplitude and decreased latency in hemiplegic patients and in reflex sympathetic dystrophy patients as a sign of sympathetic overactivity. (23), (24) There are contradictory results regarding SSR latencies. Some studies have reported the intra-individual variations for amplitudes (2-48%) and latencies (2-22%). (25), (27-30) Although Ozgocmen et al. (25) found a close correlation between SSR latencies in hands and clinical parameters, they observed no statistically significant difference in SSR distal latency between FMS patients and controls. In another study, Ulas et al. (26) investigated the autonomic nervous system dysfunction in FMS patients. They found significantly longer SSR distal latencies which are in contrast with our results. Recently Eisinger (31) reported that "fibromyalgia could be a generalized sympathetic dystrophy". There is an ANS dysfunction in FMS; however, this may not present in the same way for all patients. Some studies support diminished sympathetic activity whereas others found increased activity. These results suggest that there is no accepted point of view, but this does not change the presence of alterations in ANS which our results support.

The F-wave has proven advantages for the evaluation of the conductibility and neuron activity in proximal portions of the motor nerves since the waves occur after impulses have traveled the entire length of the motor nerves. Both F wave conduction velocity and F wave occurrence rate reflect the function of motor nerve conductivity and motor neuron activity and have been used recently in the evaluation of peripheral nerve disorders. (32), (33) Previously, Ersoz (10) evaluated nerve conduction tests in FMS patients and found no differences in F wave values performed from median, ulnar, tibial and peroneal nerves. In our study, no significant difference was found in the distal latency of the F wave between the patients and controls.

In conclusion, we can state that increased sympathetic nervous system activation occurs in FMS patients. We suggest that this abnormality could be successfully determined by SSR analysis which can be a useful and noninvasive method.

Declaration of conflicting interests

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.


The authors received no financial support for the research and/or authorship of this article.


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Tuncay CAKIR, (1) Deniz EVCIK, (2) Umit DUNDAR, (1) Ilknur YIGIT, (1) Vural KAVUNCU (1)

(1.) Department of Physical Medicine and Rehabilitation, Medical Faculty of Afyon Kocatepe University, Afyonkarahisar, Turkey; (2.) Department of Physical Medicine and Rehabilitation, Medical Faculty of Ufuk University, Ankara, Turkey

Received: September 11, 2008 Accepted: April 2, 2009

Correspondence: Tuncay Cakir, M.D. Afyon Kocatepe Universitesi Tip Fakultesi Fiziksel Tip ve Rehabilitasyon Anabilim Dali, 03200 Afyonkarahisar, Turkey. Tel: +90 272 - 340 44 56 e-mail:

Tel: +90 272 - 340 44 56 e-mail:

15th European Congress of Physical Medicine and Rehabilitation, May 16-20, 2006, Madrid, Spain.

[c]2011 Turkish League Against Rheumatism. All rights reserved.

Turk J Rheumatol 2011;26(1):38-43

doi: 10.5606/tjr.2011.006
COPYRIGHT 2011 Turkish League Against Rheumatism
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Title Annotation:Original Article
Author:Cakir, Tuncay; Evci, Deniz; Dundar, Umit; Yigit, Ilknur; Kavuncu, Vural
Publication:Turkish Journal of Rheumatology
Date:Mar 1, 2011
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