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MJ McLean, S Engström, and RR Holcomb (eds.) Published by The Floating Gallery, NY (2003)
CHAPTER 9
9.1. Introduction
The idea of using magnetic devices for the treatment of pain is not new.
Chinese and Incan civilizations used lodestones (naturally occurring mag-
netite) for a variety of ailments. The use of magnetic devices in the Orient
continues to this day in China, Korea and Japan. The Austrian physician
Franz Mesmer, treated individuals with lodestones and subsequently de-
veloped the concept of animal magnetism. Cult-like practices evolved in
which he would extend his hands over groups of people and treat their
problems, often psychological, with this so-called force (Crabtree 1993).
A committee commissioned by the French Academy of Sciences discred-
ited Mesmer in 1815. From that time forward, there was little mention
of the use of magnetic therapies in clinical therapeutics. However, a text-
book of medicine published in Philadelphia by two physicians (Stokes &
Bell 1842) included descriptions of the use of magnets to treat pain. In the
second volume there is a chapter in which a farmer with shoulder pain was
treated with an anvil-sized magnet. The magnet was hoisted with a rope
through a pulley attached to a ceiling beam. It was then lowered into close
proximity of the painful shoulder. The authors described the relief of the
farmer who felt as if he had been “touched by wind.”
The advent of magnetic resonance imaging (MRI) in the 1980’s provided
evidence that externally imposed magnetic fields can interact with human
tissues in a way that allows them to be imaged. The technique depends on
171
172 9. ROBERT HOLCOMB ET AL.
the capability of the imposed, strong magnetic field to very slightly change
the overall direction of the spin of protons in the tissue. After perturbing
these protons with radio frequency fields, they realign with the emission
of energy that can be detected, determining the spatial characteristics that
allow physiological imaging. Magnetic fields are now used routinely for
diagnosis in medicine. In contrast, our work concerns therapeutic appli-
cations of magnetic fields, especially using portable skin-attached devices
containing permanent magnets. Special challenges face those who try to
evaluate the clinical benefit of magnetic fields. In this chapter, we will
outline major issues in study design and the implications for future stud-
ies. We will also describe successful trials of therapeutic magnetic devices
against mechanical low back pain. As more is learned about how to study
magnetic field effects, it is clear that many aspects of clinical trial design
must be specially optimized for the study of magnetic devices.
the same time, what really matters is the patient’s perception of sustained
improvement by the treatment and that they continue to use it.
F IGURE 9.1. Field penetration into tissue. The graph shows how
large an area (ordinate) is exposed to a field over a given threshold
value (contours) at a given depth (abscissa) from the surface of the
device used in this study. The unlabeled iso-field lines in the figure
are (top to bottom): 3.0 mT, 10 mT, 30 mT, and 100 mT.
in the treatment of low back pain (Holcomb et al. 1991) and painful trigger
points of post-polio syndrome (Vallbona et al. 1997, see also Hazelwood,
this volume).
At the heart of understanding the discrepancies lies the problem of learning
how to study magnetic devices. Fields produced by these devices can only
be effective in the limited areas to which they penetrate. This approach
differs from the systemic administration of pharmaceuticals that may affect
more than one target along the pain-processing pathway. Non-steroidal
medications do not treat all pains effectively, and magnetic devices should
not be expected to be panaceas. Finding appropriate conditions is the first
step toward the design of discriminating studies. A seemingly obvious
point is that one should have a therapeutic effect to study before launching
a large-scale clinical study. Experience from open study of a device is a
must in order to create a successful study protocol. Even if the goal is exact
replication of another finding, it is imperative to familiarize oneself with
the application of therapeutic magnets and the inherent problems before
undertaking a masked study.
of the active device. This means that magnetic placebos must undergo
validation studies before they can be used in studies to test the efficacy
of the magnetic device. Because of this complication, there have been
no magnetic placebos for long-term trials of therapeutic magnets. The
use of magnetic placebos is more like comparing drug doses. Ideally, the
placebo will have lesser field strength, an altered spatial distribution of the
magnetic field, and a more shallow tissue penetration. These devices are
useful for longer studies, in which the patient visits the study personnel
only intermittently.
Development of magnetic placebo requires close coordination between ba-
sic researchers who can measure the magnetic field properties of the dif-
ferent devices and show in cell or animal models that the “placebo” does
not have effects similar to those of the active device. Only then should
validation studies be conducted comparing magnetic and non-magnetic de-
vices in a blinded, acute pain model to determine what, if any, efficacy the
magnetic placebo device might have in comparison with a non-magnetic
device. So far, no studies have been conducted with validated magnetic
placebos. See Figure 9.2 for a suggested design for a magnetic placebo in
which the magnetic field on the treatment side is a factor 50 below that of
the field on the side facing away from the skin when the device is in use.
The device must be easily attached to the skin and the subject should be
instructed in skin care to prevent irritation that could lead to drop-outs that
compromise the outcome of the study. The design of the device must allow
it to be placed in critical positions over pain-generating structures, either
as single devices or as arrays of devices.
Finally, it would be useful if the magnetic device under study had a known
mechanism of action. The devices used in the studies we will describe here
reversibly block action potential firing and protect neurons from swelling
and death as a result of exposure to excitotoxic amino acids. Although
the precise molecular mechanism of these cellular actions is unknown,
effects on soluble enzymes, transmembrane ion channels, and receptor-
coupled enzyme systems all lead to the possibility that proteins within
the cell change conformation in response to magnetic field exposure (see
McLean et al. in this book). These conformational changes may make the
proteins less responsive to stimulation and limit their activity in hyperex-
citable states that might be involved in producing pain, epilepsy, and other
neurological conditions with or without extensive tissue damage.
rheumatoid arthritis pain may flare and subside in an erratic manner de-
pending on supervening illnesses that enhance inflammation. Variability
can also be caused by changes in the type and amount of medication taken.
Changes in symptomatology can also change perception of pain. This can
occur when activity levels vary. In some cases, muscle contraction pain
may be added to low back pain of other etiologies. A way to control for
this is to ask patients not to change their activity levels or lift objects above
a certain weight in the course of the study. Poor sleep is frequently an ex-
acerbant of pains. Patients in chronic pain sleep poorly and are depressed.
They frequently use medications to sleep, and in some cases tricyclic an-
tidepressants. These drugs may have analgesic and adverse effects that can
confound the assessment of pain. The investigator must decide whether to
slowly taper and discontinue these medications prior to the study to achieve
a monotherapy situation during the trial, or whether to optimize the thera-
pies and then keep the drug dose constant for the study. Comorbid states
may also play a role, with pain worsening due to fever, fatigue, or other
factors.
have not been validated and pilot studies would be necessary to validate
the instruments of measure. The primary and secondary outcome mea-
sures should be determined in the context of claims desired for the device.
Many investigators believe that subjective measures of pain should not be
used. However, it could be argued that visual analog scales are subjective
and are also subject to all of the factors that we have discussed in the con-
text of variability. The VAS may be filled out with one mindset on one
day of the study, and another mind set on the other. The virtue of a scale
like the WOMAC is that there are multiple assessments for pain and others
for function and quality of life. This has the advantage of looking at the
pain from a number of different ways. It is instructive to examine pain di-
aries of individuals who have been asked to rate their pain multiple times
daily, both before and during a controlled study. In our own analysis, we
find that the patients who are keeping such diaries are able to discern ben-
efit from the active device over that from the placebo device (Figure 9.3).
Diaries resemble practical clinical methods. When patients return to their
physician, they will choose to continue or discontinue medications or other
interventions based on whether or not they are improved. If they say they
are not improved, dose adjustments or alterations in the regimen are sug-
gested. This may or may not succeed in eliciting patient cooperation in the
patient contract. Thus, we feel that it may be possible that a subjective,
self-reported scale based on frequent pain assessments may actually be de-
signed in a way that could be demonstrably superior to intermittent mea-
sures by examiners with semiquantitative instruments, such as the VAS or
WOMAC (which is itself a series of visual analog scales). Assessments by
study personnel on an intermittent basis may vary in their timing in relation
to activity. For example if the patient comes to the office by walking some
distance, he may actually have pain upon arrival in the physician’s office
due to the activity. If for the next visit he comes by car and is dropped
off and rides in the elevator, the pain may be actually less because of the
absence of activity. To control for this, patients must be instructed to keep
their activity level constant as much as possible during the study. A period
of rest in the office, perhaps an hour or more, may allow the reversal of the
activity-dependent discomfort. In studies we have alluded to above, par-
ticularly with rheumatoid arthritics, patients would come and mark VAS
scales at the same level of pain they marked prior to wearing the devices
of the study. Yet, they said their quality of life and functional capabilities
were increased so much that they did not want to give back their devices
at the end of the study. These subjective factors are rarely accounted for in
simple pain assessment scales.
magnetic devices were used to treat mechanical low back pain and knee
pain with statistically significant results (Holcomb et al. 1991). The study
consisted of two 24-hour periods, one week apart, conducted at two clin-
ical research centers. Pain was assessed by study personnel at four time-
points after device placement. Patients were treated with both active and
placebo devices in random order. The devices for both groups in this study
consisted of arrays of four permanent magnets of alternating polarity in a
TM
hypoallergenic, plastic case (Magna Bloc U.S. patent 5,312,321).
9.5.1. Pilot study. To treat mechanical low back pain in the this pilot
study, seven devices were placed in a standardized pattern over the lum-
bosacral region and coccyx (see Figure 9.4). The arrays were then covered
with a thick foam pad to protect the blind. Forty-one of fifty-four subjects
were treated for mechanical low back pain and seventeen had knee pain.
For the group as a whole, pain was reduced significantly more during treat-
ment with the magnetic treatment device than with the placebo p 003
and knee pain (34% greater reduction than placebo) responded better than
low back pain (20% greater reduction than placebo). More analgesic med-
ications were taken during the placebo treatment period than during the
active treatment, but the difference was not statistically significant. The
first study was used to plan this second pilot study with two purposes: (1)
to identify elements of study design that require optimization specifically
for the testing of magnetic devices, and, (2) to help design large, placebo-
controlled trials.
These results from the pilot study are notable because a statistically sig-
nificant result was obtained with a relatively small treatment group. The
186 9. ROBERT HOLCOMB ET AL.
relevance of pain relief that was 20 - 34% better than placebo is open to
question. Put another way, is the statistically significant reduction of pain
also biologically significant? Beecher (1955) compared morphine injec-
tion to saline. He found that the placebo effect was greatest in the imme-
diate postoperative period. Fifty-two percent of patients had pain relief
after morphine subcutaneously. Forty percent of patients had pain relief
after placebo injection. Placebo accounted for 77% of the pain relief thus
making morphine 23% more effective than placebo. Since morphine is
considered to be a gold standard of pain relief, one might boldly say that
pain relief by some magnetic fields approaches that of morphine.
TABLE 9.1. Low back pain study results. Short-term pain score
reduction for MagnaBloc- and Placebo-treated subjects (N 77).
MeanSD reduction from baseline is recorded. A two-tailed t-
test was used to evaluate the significance of the differences be-
tween the two treatments. VAS=Visual analog scale (0–100);
NRS=Numerical response scale (0–10).
9.6. Conclusions
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