R Cork, P Wood, N Ming, C Shepherd, J Eddy, L Price
R Cork, P Wood, N Ming, C Shepherd, J Eddy, L Price. The Effect of Cranial Electrotherapy Stimulation (CES) on Pain Associated with Fibromyalgia. The Internet Journal of Anesthesiology. 2003 Volume 8 Number 2.
Subjective pain intensity was the primary measured variable in a double-blind crossover study examining the effect of cranial electrotherapy stimulation (CES) on the pain associated with fibromyalgia. Initially, 39 patients were randomly allocated to CES and 35 patients were allocated to a sham group. Measurements taken at baseline and after three weeks included pain intensity, McGill Pain Score, tenderpoint score, profile of mood states, and Oswestry Score. Three weeks after crossover, measurements were repeated. Significant CES effects were identified, revealing an improvement in pain intensity, McGill Score, tenderpoint score, and profile of mood states (p<0.05). However, no significant effect was observed on Oswestry Score, which is a score identifying functional effects of pain. This study reveals that CES could play a significant role in the treatment of pain associated with fibromyalgia; however, the long-term effects on disability remain to be studied.
Supported by a grant from the Department of Anesthesiology, LSU Health Sciences Center. No financial support was received from the makers of the Alpha-Stim™; however, Electromedical Products International, Inc. did loan the authors the Alpha-Stim™ units necessary to do the study.
In a nod to Lewis Carroll, Arthur Weinstein has referred to fibromyalgia as not so much “a grin without a cat,” but a “frown without a cat.”1 In fact, so little is known about fibromyalgia that many indignant academicians question its existence. Unfortunately for us clinicians, the parade of patients presenting daily at our offices must be addressed. We have to do something. As a result, we are constantly looking for something new to do.
Cranial electrotherapy stimulation (CES) may be that something. It is a form of electrical stimulation that has already been approved by the FDA as a drug-free treatment for anxiety, depression, and insomnia, all of which have been identified as common comorbidities in patients with fibromyalgia. CES typically involves the passage of microcurrent levels of electrical stimulation across the head for from 20 minutes to an hour daily for a few days to a few weeks. Kirsch has published a review of over 150 human and animal studies regarding CES.2 A recent series of meta-analyses on the effectiveness of CES has also been recently published.3
The purpose of this clinical study was to examine the effect of CES on a group of patients with a diagnosis of fibromyalgia. The primary variable was pain intensity, as measured by the patient using a numerical scale of 0 (no pain) to 5 (worst pain possible). Secondary measurements included tenderpoint score, McGill Pain Score, Profile of Mood States (POMS), and Oswestry Score.
After approval from the LSU Health Sciences Center—Shreveport IRB, patients 22-75 years of age presenting at the LSU Pain Clinic with a diagnosis of fibromyalgia were randomly assigned to either a Sham Group or a Cranial Electrotherapy Stimulation (CES) Group. The diagnosis of fibromyalgia was verified using the criteria set forth by the American College of Rheumatology.4 Exclusion criteria included pregnancy and presence of implanted pacemakers, pumps, or stimulators, as well as the presence of superficial or internal ear infections. No change was made in the medical management of the patient during the study.
All patients were given a CES device that would provide either subsensation treatment or sham treatment. The Alpha-Stim CES device was used (Electromedical Products International, Inc., Mineral Wells, TX, http://www.alpha-stim.com). Each device was preset to provide 1 hour of 100 µA, modified square-wave biphasic stimulation on a 50% duty cycle at 0.5 Hz, and to automatically turn off at the end of one hour. All treatment was given via electrodes clipped to the ear lobes (Figure 1). Location of electrodes on the ear lobes is illustrated in Figure 2. Sham treatment was provided by identical ear clip electrodes that did not pass current. All staff, the physicians, and the patient were blind to the treatment conditions. At the end of three weeks, the CES Group was unblinded, and the Sham Group was given the option to receive active therapy for an additional three weeks.
Initial measurements were taken at baseline, prior to commencement of the treatment period. These measurements included:
Following the baseline tests, the subjects were taught how to use the CES unit, and they were instructed to use it every day for 1 hour over a 3-week period. At the end of 3 weeks, the subjects returned to the Pain Clinic, and all the above tests were repeated. At that time, the key to the blinding was broken, and the patients in the Sham Group were given the option to receive CES for an additional three weeks. Those who elected to do so returned to clinic after the three-week period and were re-tested.
Data were analyzed with repeated-measures analysis of variance, with least-significant-difference
A total of 74 patients were studied, 39 in the CES Group and 35 in the Sham Group. Following the unblinding at 3 weeks, 23 patients in the Sham Group elected to cross over to active treatment for three weeks. Of the 74 patients, 70 were female. Average age was 53 (min 22 yrs, max 75 yrs); average duration of symptoms was 7.3 years (min 1 yr, max 21 yrs).
All measurements are graphically depicted in the accompanying Figures 3-5, 7-8. There were no differences detected at baseline between the CES Group and the Sham Group for any of the measurements. The Pain Intensity Score, the Tenderpoint Score, and the POMS Score were all significantly less in the CES Group compared to the Sham Group at 3 weeks (p<0.01). For those patients in the Sham Group who elected to receive treatment with CES over the subsequent 3-week period, all measurements except the Oswestry Score were significantly improved over baseline (p<0.001).
We have demonstrated that active treatment with CES results in significant improvement in a number of clinical parameters associated with fibromyalgia, including subjective pain intensity, McGill Pain score, tenderpoint score and self-reported anxiety (per POMS score). The results of our investigation appear to be most encouraging, given the refractory nature of fibromyalgia pain to conventional pain management. Taken together, one might conclude that CES was indeed able to favorably alter the patient's clinical state, while failure to improve Oswestry scores, a measure of subjective disability, may reflect more of a trait quality in this sample of individuals on referral to a tertiary care pain management program. The Oswestry Scale was originally used to quantitate disability,5 rather than as a functional assessment of pain, so one might reasonably conclude that longer follow-up would be necessary to see changes in the Oswestry scores.
The suggestion that CES may be efficacious in the treatment of fibromyalgia begs the question by what mechanism? It could be just a matter of improved sleep patterns, which CES has been shown to induce.3 However, low frequency, repetitive stimulation may hold the key to understanding our success. Specifically, studies using sub-dissociative doses of the non-competitive n-methyl-d-aspartate (NMDA) receptor antagonist ketamine have demonstrated the pain of fibromyalgia to be uniquely related to hyperactivity of this subtype glutamate receptor in a majority of fibromyalgia patients.10 Likewise, fibromyalgia pain has been theoretically linked to transformation of NMDA receptor function specifically within the hippocampal formation11, wherein they are known to participate in the modulation of tonic pain.12 Whereas high frequency (i.e. tetanic) stimulation of hippocampal NMDA receptors produces long-term potentiation, low frequency stimulation has been demonstrated to down-regulate NMDA receptor function, resulting in long-term depression.13,14 Thus, the efficacy of CES in alleviating fibromyalgia pain may be related, at least in part, to an alteration in the functional parameters of supraspinal NMDA receptors that hypothetically contribute to the experience of chronic widespread pain.
The repetitive nature of the stimulus may hold the key to understanding the success of CES in the treatment of chronic pain. Repetitive stimulation has been long associated with wind-up, neuroplasticity, and central sensitization. Many of these same processes are mediated by the NMDA receptor. Could it be that the subsensory or low-sensory stimulation of CES interferes with the adverse neuroplastic and NMDA changes associated with neuropathic pain? Is there a neuropathic Gate Control Theory? As poorly defined or accepted as fibromyalgia be, it could hold the secret to a new area of study involving neuropathic pain.
CES appears to be an effective, well-tolerated treatment for the treatment of fibromyalgia. Those involved in the treatment of fibromyalgia should include it in their clinical armamentarium, given the demonstrated safety of this non-invasive modality.