Chronic pain is one of the most troublesome and disabling conditions that physicians are called upon to treat. However, current options for the treatment of more severe chronic pain are generally flawed by reason of being ineffective in controlling anything more than mild to low-moderate pain, or because they are associated with significant side effects or risks of drug tolerance, dependence and addiction. The rapidly expanding field of biomagnetics potentially offers a variety of therapeutic modalities that may be of clinical value, especially in patients who have pain that is resistant to more traditional therapeutics. Among these modalities, PEMF is unique. To begin with, as opposed to a transcutaneous electrical nerve stimulation unit – an electrical device that is associated with currents, such that electrons actually pass through the tissues to which the device is being applied, thereby providing localized pain relief (27
) – PEMF is an electromagnetic process that is not associated with currents, but with magnetic fields that can be applied to the brain to generate more global pain relief. Secondly, as opposed to a variety of oscillating fields, such as repetitive transcranial magnetic stimulation, which primarily relies on the physical attributes of the electromagnetic field, PEMF utilizes particular aspects of the pulse-form shape to affect a clinical response. An analogy to clarify this distinction would be to think of oscillating fields as using the percussive effect of a sound wave, and PEMF as using the information carried within a complex form of that wave, such as that created by human speech. The PEMF that we use exclusively are also of lower power and frequency than virtually all other modalities, so that theoretically, they should be associated with fewer adverse effects.
Considerable prior work has demonstrated the beneficial effects of PEMF in various animal models. One of the first notable findings was the apparent attenuation of morphine-induced analgesia in mice by magnetic resonance imaging (52
). Subsequently, Prato et al (1995) assessed the potential mechanisms for the previously observed analgesia in the land snail when subjected to a hot plate (53
). It was determined that analgesic effects occur only with time-varying magnetic fields and at certain combinations of frequency and amplitude, and that the effects are influenced by the presence or absence of light (54
). Specifically, they considered whether the magnetic field effects involve an indirect induced electric current mechanism or a direct effect. Findings suggested that, both in light and dark, the effect of a pulsed extremely low-frequency magnetic field is mediated via a direct magnetic field detection mechanism, rather than an induced current.
In a further study on the land snail, again subjected to extremely low-frequency magnetic fields, it was demonstrated that exposure to a specific electromagnetic field, the Cnp, increased the latency of the snail’s nociceptive response to a hot plate, while a random pulsed low-frequency magnetic field did not (51
). Moreover, this Cnp analgesia was significantly decreased by administering the opioid antagonist, naloxone, again suggesting that Cnp’s antinociceptive effects somehow involve the augmentation of endogenous opioids. Subsequently, this same effect was demonstrated in mice (42
As a result of these early animal studies, in conjunction with more recent animal work, further studies involving humans have documented effects both on standing balance (44
) and pain (41
). The mechanisms by which these effects occur are not fully understood. However, there is evidence that PEMF actually change brain wave activity, suggesting that the symptom-altering effects of electromagnetic waves are the result of a direct effect on central nervous function (45
). Moreover, the blocking effects of naloxone strongly suggest that the electromagnetic forces affect the release of endogenous opioids, probably via direct influences upon the brain’s limbic system.
In our most recent research, we have shown that low-frequency PEMF can be delivered to adults with chronic pain by means of a headset, with minimal to no inconvenience or side effects, at least in the short term. Moreover, even though our study was small, the evidence suggests that PEMF, so delivered, may have significant analgesic effects, at least in patients with FM.
That there seemed to be a differential effect between those with FM and those with more localized MSK pain or inflammatory pain was a bit surprising. In an earlier study, patients with chronic knee pain receiving a two-week exposure to a magnetic field experienced a significant improvement in the individual’s levels of self-rated pain and physical functioning (56
). On the other hand, given the perceived central neural mechanism operating in FM (15
), it makes some sense that this population would be most responsive to a therapeutic modality delivered via a headset. The pain associated with OA, for example, is believed to arise from irritation of nociceptors in and around the joint itself. In the joint, tissues containing nociceptors include the joint capsule, ligaments and bone. Nociceptive stimuli are likely to emanate from one or more of these locations in people with OA (57
). This peripheral origin of OA pain is the likely reason for its therapeutic response to nonsteroidal anti-inflammatories (58
), a response that is not seen in patients with FM (59
). In early RA, much of the pain and stiffness likely arises from irritation of the joint capsule (synovium), secondary to inflammation (60
), whereas later in RA, it also results from bony microfractures and other tissue disruption, similar to what is seen in late OA (62
). In both instances, the pain mechanisms seem to originate peripherally, again making relief from a therapeutic modality targeting the brain seem less likely.
Our FM sample was different than those we recruited who did not have FM, in that a much greater percentage were female, the FM patients were somewhat younger, and their baseline pain severity scores were generally higher. It is conceivable, then, that the differential response of FM to PEMF was the result of one of these potential confounders. However, both on univariate and multivariate analyses, none of these variables explained the seemingly selective response of FM to PEMF. Our sample was too small, however, to allow for full multivariate testing. A larger sample would allow for linear or logistic regression to determine the relative impact of each of these variables, including treatment arm, on change in pain.
In the present study, the percentage of pain reduction was not uniform throughout the first week of study in patients exposed to PEMF or to sham treatment, and in either those with FM or without. This fluctuation may have been due to the headsets not fitting each individual correctly, which may have led to discomfort, and therefore, to interference, at least at times during the treatment week. Increased patient training and a longer duration of treatment to allow for enhanced use of the headsets may result in a greater effect of treatment than we observed.
Over the entire four weeks of observation, the group of subjects with FM who received PEMF exhibited changes in VAS pain severity that were most consistent with a treatment response. Specifically, pain severity declined by the end of the first day and continued to decline throughout the seven days of treatment; over the entire week, pain levels were lower than in the sham group, with the intergroup difference increasing steadily as the week progressed. By the end of the first day after cessation of PEMF, pain had increased dramatically, almost to pretreatment levels; pain fell on the second post-treatment day, and then steadily increased through the washout week. Pain VAS remained high at the end of weeks 3 and 4. Subjects without FM receiving PEMF had a somewhat delayed decline in VAS pain severity but to a lesser degree, and it only fell below the pain levels of the sham group by the seventh day. As with those with FM, a rebound increase in pain was noticed on the first day post-treatment, but pain fluctuated thereafter. Graphically, there was no clear trend toward decrease or increase in pain severity in either sham group.
The net reduction in pain on the VAS was equivalent to a low to moderate dose of opioid analgesic in PEMF-exposed patients (63
). It has often been pointed out that both the endogenous and exogenous opioid systems are influenced by PEMF exposure sessions in animals and humans (68
). Moreover, when an opiate such as morphine is used in combination with PEMF, the side effects of the opiate may be reduced (42
). Consequently, we believe not only that PEMF should be investigated further as a replacement for opioid analgesics in some patients with chronic pain, in particular those with FM, but that PEMF may also warrant investigation as a supplement to opioids, especially in patients with more severe pain.
In our study, the overall net percentage change for PEMF was 20%, corresponding to a percentage change of 24% and 4% for treatment and placebo, respectively. A subset analysis on patients (n=15) who reasonably complied with the protocol (used device 12 or more applications out of 14) and whose intake VAS was seven or higher revealed a net change of 38%. Both values compare favourably with the intent-to-treat responses of 16% to 23% observed with low to low-intermediate dose sustained or immediate-release oxycodone (65
); and with the 9% to 12% observed with low-dose sustained-release morphine (68
Net analgesic efficacy of opioids in chronic musculoskeletal pain
Having said this, we urge caution to every reader, given that our study has undeniable limitations. To begin with, the study produced only marginally significant results, so that it is possible that the seemingly beneficial effects of PEMF in our study were merely the result of chance. Second, our study only followed patients for a total of four weeks, and we only delivered treatment for one week. It is conceivable, although we think improbable, that use of PEMF may result in significant rebound exacerbation of pain or, alternatively, that PEMF may be subject to tolerance, in the same way that many patients ultimately develop tolerance to the analgesic effects of opioids, consequently requiring higher and higher doses to achieve satisfactory pain relief. Clearly, longer-term follow-up is warranted to address this concern.
One data concern that arises is that there was a day 1 difference in pain VAS score of 1.1 between FM subjects who ultimately received PEMF (VAS=9.6) and FM subjects who received the sham treatment (8.5); this compares to a difference of just 0.5 between subjects without FM who received PEMF (8.9) versus sham treatment (8.4). Because there is a statistical tendency for values to regress to the mean, any such tendency among the FM subjects would likely be greater than among the remaining subjects, which is a potential source of type I error (identifying a difference which does not truly exist). A larger study clearly is warranted to offset this potential bias, because larger, random samples of FM subjects and patients with other sources of pain would tend to reduce any chance differences between the within-disease subgroups (PEMF versus sham) at baseline.
Another source of bias might pertain to the level of physical activity exerted by FM versus non-FM subjects. Given the high rate of debilitating fatigue reported by FM patients (13
), it may be that any improvement in pain in this group was associated with less of an increase in activity than among those without FM. If increased activity increases pain, the increased level of activity among non-FM subjects may have offset any analgesic effect, relative to what was experienced by those with FM. This would be another potential source of type I error. Future research should assess outcomes beyond pain severity, including the levels of activity and function, to determine if there is any potentially confounding interactions between pain severity and these other variables.
Finally, 18 of our initially randomly assigned 50 patients dropped out of the study, including 10 with FM. Fifteen never received a single treatment, which is a usual criterion for inclusion in intent-to-treat analyses. The remaining three, two from the PEMF group and one from the sham group, were excluded on the basis of no longer meeting inclusion criteria at the time of their day 1 assessment, due to exceedingly low pain severity scores. Had we performed an intent-to-treat analysis, these three should have been included, because they did receive some treatment. Nonetheless, we felt justified excluding these three subjects because they were almost equally distributed between the two treatment arms and between the FM versus no FM groups (two versus one), because they were so few in number, and because none of the three received more than a few treatments. In addition, ours essentially was a negative study, albeit with enticing results in FM patients which warrant further study.
Consequently, we believe that our study forms another crucial step in the development of a novel therapeutic option for patients with chronic pain and, in particular, for patients with disorders like FM, in which central mechanisms of pain appear to predominate. Traditionally, this has been a group that is poorly served by existing treatments. Our hope is that PEMF may offer a very safe, yet effective alternative for at least some these patients. Clearly, a larger randomized and double-blinded clinical trial, focusing especially on FM patients, is warranted. Based upon the variances determined in our study, we predict that a study with 25 FM subjects per group would demonstrate a 25% reduction in VAS pain severity, even allowing for 35% drop-out rate (so that 16 per group complete the study). However, given the potential confounding effect of pretreatment pain levels, and the preference for intent-to-treat analysis, a study with 25 to 30 subjects per group completing treatment would be preferable.