23
Interventional and Nonpharmacological Therapies
for Neuropathic Pain
Mark S. Wallace, MD
Department of Clinical Anesthesiology, University of California, San Diego, La Jolla, California, USA
Educational Objectives
1. To review the challenges of applying evidence to interventional therapies.
2. To describe current and emerging implantable therapies to treat chronic neuropathic pain.
3. To outline some nonpharmacological therapies to
treat chronic neuropathic pain.
Interventional Therapies
Applying Evidence to Interventional Therapies
In recent years, interventional therapies to treat
chronic pain have come under scrutiny owing to a
lack of evidence supporting efficacy. This has led to
the development of consensus guidelines based on
the evidence as well as on expert consensus [35].
In 1990, the Institute of Medicine defined clinical
guidelines as “systematically developed statements
to assist practitioner and patient decisions about
appropriate health care for specific clinical circumstances” [18]. In 2011, this definition was revised as
“statements that include recommendations intended
to optimize patient care that are informed by a systematic review of evidence and an assessment of the
benefits and harms of alternative care options ” [20].
The new definition acknowledged that, for many
Pain 2014: Refresher Courses, 15th World Congress on Pain
Srinivasa N. Raja and Claudia L. Sommer, editors
IASP Press, Washington, D.C. © 2014
clinical domains, high-quality evidence is lacking or
even nonexistent. Despite such constraints, guideline
developers should still be able to produce trustworthy clinical practice guidelines.
Unlike the case for pharmaceuticals, there are
obvious challenges in applying high levels of evidence
to surgical or minimally invasive procedures. These
challenges include ethical limitations of blinded surgical and sham procedures, prohibitive costs, and the
need to recruit adequate numbers to complete a trial.
In addition, there are wider variations in the definition of successful outcomes. For example, an American Academy of Neurology task force reported on
the efficacy of epidural steroid injections (ESIs). They
reviewed all of the literature on ESIs for lumbar radiculopathy and concluded that there is evidence that
supports pain relief for up to 3 months; however, they
could not recommend the routine use of ESIs for lumbar radiculopathy [2]. This conclusion is contrary to
the general opinion that 3 months of pain relief from
a single ESI is both clinically meaningful and cost-effective. A recent recommendations paper on interventional management of neuropathic pain from the IASP
Special Interest Group on Neuropathic Pain (NeuPSIG) concluded that owing to the paucity of highquality clinical trials, no strong recommendations can
be made. However, on the basis of the available data,
they recommended against using sympathetic blocks
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for postherpetic neuralgia or using radiofrequency lesions for radiculopathy [16].
Interventional treatment guidelines should
serve two purposes: (1) to apply evidence-based medicine to improve patient selection and outcome and (2)
to implement best clinical practices for techniques to
improve outcome and safety. The latter point is important, and often overlooked, because as clinical experience evolves, risks emerge from interventions that have
long been felt to be safe. An example is the transforaminal injection of particulate steroid, in which many reports of serious injury and death are emerging [43].
General Principles of Interventional Therapies
for Neuropathic Pain
The application of interventional therapies for the treatment of neuropathic pain is quite different from that for
nociceptive pain. In addition, the application will differ
between noncancer and cancer pain. For example, with
the exception of cryoablation, neuroablative therapies
are rarely used to treat neuropathic pain because an
additional insult/injury to the nervous system carries a
high risk of increasing the pain from a preexisting nervous system injury. An exception to this rule is in the
treatment of terminal cancer pain, given that the pain
relief of the neurolytic procedure will outlast the life of
the patient. In other words, the time it takes for the additional injury from the neurolytic to cause pain is longer than the life of the patient.
The location of interventional therapies in
the pain treatment continuum will depend on the invasiveness of the therapy. Simple treatments such as
epidural steroids (although controversial in the treatment of neuropathic pain) or sympathetic blockade
might be used early on, whereas spinal cord stimulation (SCS) or intrathecal drug delivery systems (IDDS)
would be used only after more conservative therapies
have been tried. However, recent controversy has
emerged with regard to the use of SCS over chronic
opioid therapy for noncancer pain. With the increasing reports on the risks and limited value of opioids in
chronic pain, SCS is being favored as a more conservative and safe therapy.
Although a number of interventional therapies
are used in the management of chronic pain, this chapter will focus on implantable therapies used to treat
neuropathic pain. NeuPSIG’s evidence-based guidelines
for other interventional therapies were reviewed recently by Dworkin et al. [16].
Mark S. Wallace
Neural Stimulation
Electrical Basics
An understanding of basic electrical physics is critical for the application of SCS clinically. Ohm’s law is
as follows: Voltage (V) = Current (I) × Resistance (R).
We can control V and I, but not R. Patient factors that
affect R include cerebrospinal fluid (CSF) depth, fluids
(CSF, blood, injectates), dural thickness, epidural fat,
and scar tissue. There are currently three systems on
the market, with the main differences based on Ohm’s
law: (1) single-source voltage-controlled, (2) singlesource current-controlled, and (3) multisource current
controlled. Although there are significant technologies
behind these three systems, there are no controlled
studies comparing efficacy. The stimulation pulse is the
energy applied to the nerve and is characterized by the
strength (amplitude) and duration (pulse width). Four
parameters are controlled: (1) electrode polarity, (2)
amplitude, (3) pulse width, and (4) frequency.
Polarity
For current to flow and nerve depolarization to occur,
there must be at least one negative (cathode) and one
positive (anode) electrode. Depolarization occurs under the cathode. An increased ratio of anodes to cathodes will increase the charge density under the cathode.
A decreased ratio of anodes to cathodes will reduce
the charge density under the cathode. This ratio controls the shape and density of the electrical field, which
in turn will determine the nerve fibers in the spinal
cord that are activated. More closely spaced electrodes
will penetrate the current with more focus and depth,
whereas more widely spaced electrodes will spread the
current more widely and superficially. Multiple electrodes placed cephalad/caudad and medial/lateral over
the spinal cord can be used to steer the current.
Amplitude
Defined as the strength of the stimulus measured in
volts or milliamps, amplitude is the primary control
over the intensity of the stimulus sensation. The higher
the amplitude, the greater the size of the electrical field,
resulting in the depolarization of nerves over a larger
area. Higher amplitudes can result in painful sensations.
Pulse Width
Defined as the duration of the stimulation pulse, pulse
width is typically measured in microseconds. Greater
pulse width will cause the stimulation to stay on longer,
Interventional and Nondrug Neuropathic Pain Therapies
249
resulting in depolarization of fibers with higher thresholds (sequential recruitment). Adjustment in pulse
width can activate fibers that normally would require
higher amplitudes, resulting in painful stimulation.
Pulse width can be used in conjunction with amplitude adjustment to control the intensity of the stimulation pulse.
are from single sites, and there is a need for multicenter
randomized controlled trials with larger numbers. An
attempt was made to perform such a trial. However
after over 2 years, the study was prematurely terminated due to difficulties in enrolling subjects. This failure
stresses the challenges of performing high-quality studies on interventional therapies to treat pain.
Frequency
Burst Stimulation
Frequency is defined as the number of stimulation pulses delivered per second. Higher frequency increases the
number of action potentials delivered by the nerve up
to a point at which conduction block can occur. Changes in frequency result in changes in sensation. Low frequency results in a pulsing sensation, and high frequency results in a flutter sensation. Higher frequencies will
increase the rate of battery depletion.
Burst spinal cord stimulation is an emerging technique that uses multiple bursts of stimulation that are
paresthesia free. Traditional stimulation consists of a
single higher-amplitude waveform. Burst stimulation
uses multiple smaller-amplitude, higher-pulse-width
waveforms in the same frequency range as traditional stimulation parameters. For example, a traditional
waveform is 5 mA, 200 μs, and 40 Hz. A similar burst
stimulation waveform is five 1-mA, 1000- μs bursts
within a 40-Hz frequency. A typical burst stimulation parameter is five 1-μs bursts separated by 1-μs
intervals in a 10-μs period, which results in a paresthesia-free stimulation. The lateral thalamic cells fire
in a tonic pattern, and medial thalamic cells fire in
a burst pattern. Therefore, the theory behind burst
stimulation is that the medial thalamic cells are activated, resulting in a dissociation from the pain. These
observations have been confirmed with studies showing that burst stimulation produces significantly more
alpha activity in the dorsal anterior cingulate cortex
(the medial pain system), which controls the affective/attentional component of the pain experience
[15,22,25,34]. De Ridder et al. showed a statistically
significant benefit of burst stimulation versus tonic
for the general pain visual analogue scale. There was
also a significant benefit of burst stimulation versus
tonic stimulation with respect to attention to pain and
attention to changes in pain. Further studies are currently in progress [14,15].
Spinal Cord Stimulation
Conventional Paresthesia Stimulation
Spinal cord stimulation (SCS) is indicated for the treatment of neuropathic pain. Neuropathic pain that is
continuous and unchanging responds the best. SCS
is not indicated for activity-related non-neuropathic
pain. The goal of SCS is to apply sufficient electrical
current over the dorsal columns to result in paresthesias that overlap the painful area while minimizing
paresthesias in extraneous areas. The most common
indication is failed back surgery syndrome with leg
pain. Less common indications are peripheral nerve
injury, complex regional pain syndrome (CRPS), and
painful peripheral neuropathy [27]. In these three latter syndromes, overlapping paresthesias can be challenging, and it is more common for patients to report
pain in spite of overlapping stimulation. The mechanism of action is thought to be based on the gate control theory of pain by selectively depolarizing largefiber afferents in the dorsal column, thus closing the
gate to small-fiber afferents that transmit pain into the
spinal cord [37]. Animal studies also suggest that SCS
may alter neurotransmitter release in the sympathetic
nervous system and in GABAergic interneurons of the
spinal cord. CSF concentrations of glutamate, glycine,
and serotonin are affected by SCS. SCS does not appear
to alter the μ-opioid receptor system [32].
The cost-effectiveness of SCS versus reoperation or versus conventional medical management for
failed back surgery syndrome has been shown in randomized controlled trials [28,38]. However, these trials
High-Frequency Stimulation
High-frequency stimulation uses frequencies up to 10
kHz, pulse width up to 1000 ms, and amplitude up to
15 mA, which results in paresthesia-free stimulation.
The exact mechanism of pain relief is unclear, but preclinical studies have shown that a high-frequency alternating-current sinusoidal waveform applied to a nerve
will result in a reversible block of activity [3]. This block
occurs in three phases: an onset response, a period of
asynchronous firing, and a steady state of complete or
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partial block. This technology is currently available in
Europe and Australia, with clinical trials ongoing in the
United States. Due to the high frequencies used, energy
consumption is high, thus requiring a rechargeable battery. This method is used primarily to treat back pain,
with some effect on lower-extremity pain. Intraoperative paresthesia mapping is not necessary, and leads are
placed anatomically over T9 in the midline, thus shortening procedure time. A U.S. pilot study in 24 patients
with back and leg pain demonstrated a significant reduction in back and leg pain [49]. A European study
conducted in 83 patients with primarily low back pain
was successful in 72 patients. Long-term follow-up to
12 months showed a significant reduction in both back
and leg pain. There was also a significant improvement
in the Average Oswestry Disability Index Score. Sleep
disturbance was improved, and patient satisfaction was
high [50]. Perruchoud et al. performed a blinded, shamcontrolled study interspersing high-frequency and
sham stimulation between conventional stimulation periods. They demonstrated no difference between highfrequency and sham stimulation. However, they placed
the leads for conventional stimulation with frequencies
of 5 kHz [41]. The current system approved in Europe
uses 10 kHz with all leads placed a specific location,
which may explain the results.
Dorsal Root Ganglion Stimulation
The dorsal root ganglion (DRG) has an important role
in the development and maintenance of chronic neuropathic pain. In addition, CRPS, distal leg and foot pain,
inguinal pain, and truncal pain have been difficult areas to target with conventional paresthesia stimulation.
Therefore, the DRG is a reasonable target for stimulation to treat these challenging pain syndromes. The
predictable location of the DRG in the epidural space
and the lack of overlying CSF allows for increased energy efficiency and lower energy consumption than
traditional and high-frequency spinal cord stimulation.
Leads are placed into the epidural space and steered
out of the target neural foramen to overlay the DRG.
Advancing the lead into the epidural space creates retaining loops that reduce lead migration. A prospective study was performed in 32 patients with chronic
pain of the limbs and/or trunk. At 6 months after implant, more than half of the participants reported 50%
or greater pain relief, with the proportions experiencing 50% or more reduction in pain specific to back, leg,
and foot regions being 57%, 70% and 89% respectively.
Mark S. Wallace
They concluded that areas hard to treat with SCS (such
as the feet and trunk) may be more amenable to DRG
stimulation [31].
Peripheral Nerve Stimulation
Peripheral nerve stimulation (PNS) was first used over
40 years ago, but it fell out of favor because of the need
for an invasive cut-down for lead placement [52]. SCS
came into favor owing to its success and the ease of lead
placement. However, with recent advances and new
techniques, there is renewed interest in PNS to treat
chronic neuropathic pain, partly because SCS is not as
effective in the treatment of peripheral nerve injuries.
There are several ongoing clinical trials with DRG stimulation for the treatment of traumatic nerve injury and
CRPS. The mechanism of PNS is unclear, but some suggest that it changes the neurotransmitter milieu of the
peripheral nerve to relieve pain. The classic gate control
theory has also been suggested [6,51].
Indications for PNS include pain in the distribution of an accessible peripheral nerve. The most
common nerves to be treated are the supraorbital, infraorbital, greater occipital, ulnar, median, suprascapular, intercostal, ilioinguinal, iliohypogastric, genitofemoral, lateral femoral cutaneous, saphenous, sciatic,
posterior tibial, superficial peroneal, and sural nerves.
With the use of ultrasound, the percutaneous placement of leads is becoming more common, at least in
trials. The same concepts of electrical physics described
for SCS also apply to PNS [44].
There are few studies on the long-term outcomes of PNS. Deer et al. published a recent study
showing relief from a device that does not require an
implantable pulse generator. They are currently conducting a multicenter trial. Hassenbusch and StantonHicks published a study evaluating PNS for CRPS.
The success rate was more than 60% with devices that
would now be considered antiquated. There are also favorable studies evaluating PNS to treat migraine (with
occipital nerve stimulation), facial pain, and axial spine
pain [8].
Intrathecal Drug Delivery
Intrathecal drug delivery (IDD) is considered an invasive and labor-intensive therapy. Therefore, appropriate patient selection and failure of more conservative
therapies are essential. Indications for IDD include: (1)
somatic/nociceptive pain, (2) neuropathic pain that has
Interventional and Nondrug Neuropathic Pain Therapies
failed to respond to spinal cord stimulation (if indicated), (3) multiple pain sites with truncal/axial pain, and
(4) static or changing pain. Table I summarizes selection criteria for IDD [55].
Table I
Patient selection for intrathecal therapy
Malignant Pain
Life expectancy greater than 3 months
Inadequate pain relief and/or intolerable
side effects from systemic agents
Favorable response to screening trial
Nonmalignant Pain
Objective evidence of pathology
Inadequate pain relief and/or intolerable
side effects from systemic agents
Lack of drug-seeking behavior
Favorable response to screening trial
Patients with a psychological profile deemed
appropriate for IDD therapy have better outcomes than
those deemed inappropriate; therefore, psychological
clearance is important to success. Psychological exclusion criteria include: (1) active psychosis, (2) active suicidality, (3) active homicidality, (4) major uncontrolled
depression or other mood disorders, (5) somatization
or other somatoform disorders, (6) alcohol or drug dependency, (7) compensation or litigation resolution, (8)
lack of appropriate social support, and (9) neurobehavioral or cognitive deficits [4]. The choice of screening
technique for IDD remains controversial. Both continuous infusion and bolus dosing have been used. A recent polyanalgesic consensus panel published the first
recommendations for IDD (Table II) [9].
Table II
Recommended doses for
intrathecal drug bolus trialing
Recommended
Drug
i.t. Bolus Dose
Morphine
0.2–1.0 mg
Hydromorphone 0.04–0.2 mg
Ziconotide
1–5 μg
Fentanyl
25–75 μg
Bupivacaine
0.5–2.5 mg
Clonidine
5–20 μg
Sufentanil
5–20 μg
Even more controversial is whether to withdraw systemic opioids prior to trying IDD. Advantages
include: (1) reversal of tolerance, (2) identification of
patients with strong physical dependence, (3) possible
identification of patients with psychological dependence and addiction, and (4) possible reduction of total
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IDD dose over time. Disadvantages include increasing
pain and suffering while the patient is off the opioids
and delays in initiation of IDD. Guidelines have been
published for the management of both cancer and noncancer pain (Tables III–VI) [10,11].
Table III
Recommended starting dosage range and titration
for intrathecal drugs
Drug
Recommended
Starting Dose
Incremental
Increase
Morphine
0.1–0.5 mg/day
0.5 mg
Hydromorphone
0.02–0.5 mg/day
0.1 mg
Ziconotide
0.5–2.4 μg/day
10 μg
Fentanyl
25–75 μg/day
2.5 μg
Bupivacaine
1–4 mg/day
0.1 μg
Clonidine
40–100 μg/day
1 mg
Sufentanil
10–20 μg/day
10 μg
Source: Modified from Deer et al. [13].
Drugs Used for IDD
Opioids
Agonism of pre- and postsynaptic μ-opioid receptors in
the dorsal horn reduces presynaptic neurotransmitter
release and hyperpolarizes the postsynaptic membrane.
Morphine is the gold standard and the only opioid with
U.S. Food and Drug Administration (FDA) approval for
IDD. Other commonly used opioids include hydromorphone, fentanyl, and sufentanil. Side effects include respiratory depression with overdose, nausea, urinary retention, pruritus, and peripheral edema [24,39,40].
Ziconotide
Ziconotide is the first nonopioid approved for IDD to
treat chronic pain. Its mechanism is through presynaptic N-type calcium channel blockade in the dorsal
horn to reduce presynaptic neurotransmitter release.
Ziconotide is indicated for the management of severe
chronic pain in patients for whom IDD is warranted,
and who are intolerant of or refractory to other treatments such as systemic analgesics, adjunctive therapies, or IDD morphine. Two fast-titration trials (one
for malignant and one for nonmalignant pain) and one
slow-titration trial led to FDA approval. The malignant and nonmalignant pain study showed a 53.1% vs.
18.1% and 31.2% vs. 6% reduction in pain (ziconotide
vs. placebo), respectively; however, there was a high
dropout rate due to side effects [48,53]. A follow-up
3-week slow-titration trial in chronic pain patients
with preexisting implanted IDD pumps showed a
252
Mark S. Wallace
Table IV
2011 polyanalgesic consensus for intrathecal drugs for neuropathic pain
Line 1
Morphine
Ziconotide
Morphine + bupivacaine
Line 2
Hydromorphone
Hydromorphone + bupivacaine or
hydromorphone + clonidine
Morphine + clonidine
Line 3
Clonidine
Ziconotide + opioid
Fentanyl + bupivacaine or
fentanyl + clonidine
Line 4
Opioid + clonidine + bupivacaine
Line 5
Baclofen
Fentanyl
Bupivacaine + clonidine
Table V
2011 polyanalgesic consensus for intrathecal drugs for nociceptive pain
Line 1
Morphine
Hydromorphone
Ziconotide
Fentanyl
Line 2
Morphine + bupivacaine
Ziconotide + opioid
Hydromorphone
+ bupivacaine
Fentanyl +
bupivacaine
Line 3
Opioid (morphine, hydromorphone, or fentanyl + clonidine)
Sufentanil
Line 4
Opioid + clonidine + bupivacaine
Sufentanil + bupivacaine or clonidine
Line 5
Sufentanil + bupivacaine + clonidine
Table VI
Recommended maximum daily dose and
concentration for intrathecal drug delivery
Drug
Maximum Dose/
24 Hours
Maximum
Concentration
Morphine
10 mg
20 mg/mL
Hydromorphone
10 mg
20 mg/mL
Fentanyl
500 μg
2000 μg/mL
Sufentanil
250 μg
1000 μg/mL
Ziconotide
2.5 μg
20
Bupivacaine
10 mg
20
Clonidine
250 μg
2000
Source: Modified from Deer et al. [13].
used. It has few side effects with minimal sensory and
motor disturbances at doses <20 mg/day [55].
Clonidine
Clonidine works through agonism of pre- and postsynaptic adrenergic α2 receptors, resulting in a reduction
in presynaptic neurotransmitter release and hyperpolarization of the postsynaptic membrane. It is FDA approved for epidural use in cancer pain only; however, it
is widely used in IDD therapy. Side effects include hypotension, bradycardia, and sedation. It is often used in
combination with other IDD agents [55].
Baclofen
14.7% vs. 7.2% reduction in pain (ziconotide vs. placebo) at 3 weeks (P = 0.36). Side effects were much less
severe, and the dropout rate did not differ between
the ziconotide and placebo group [42]. Although ziconotide has a high incidence of cognitive side effects,
there is a wide margin of safety in overdose. Cognitive
side effects are reduced with slow titration. There is
no acute drug withdrawal syndrome upon cessation of
the ziconotide. Ziconotide can be used in combination
with other drugs, but there is some loss of potency
when it is mixed with morphine [54].
Local Anesthetics
Local anesthetics are widely used in IDD. They work
through blockade of pre- and postsynaptic sodium
channels. They are most commonly used in combination
with other IDD agents. Bupivacaine is most commonly
Baclofen is a GABAB agonist with antispasmodic effects through decrease release of excitatory neurotransmitters from IA, IB, and A-α afferents in the
spinal cord. Analgesic effects may be due to effects on
voltage-sensitive calcium channels. It is FDA approved
as an antispasmodic [55].
IDD Systems
There are currently two FDA-approved systems on
the market used to treat chronic pain. The Medtronic
Synchromed II comes in 20- and 40-mL reservoir volumes. It uses a programmable peristaltic rotor system
for variable rate delivery. A patient-controlled bolus
dosing allows for treatment of breakthrough pain.
It has a 5-year battery life and is FDA approved for
morphine, baclofen, and ziconotide. The Flowonix
Prometra pump uses a pressurized gas chamber as
Interventional and Nondrug Neuropathic Pain Therapies
the driving force with a programmable flow-metering
valve for variable rate delivery, resulting in much lower energy requirements and thus longer battery life
(10 years) [19].
Morbidity Related to IDD
The most common cause of morbidity relates to catheter problems. The track record for drug delivery by
the system is quite good, with rare reports of system
over- or under-infusion. Occasionally, the system can
shut down if the rotor stalls, resulting in acute drug
withdrawal. Filling of the pump pocket with high drug
concentrations, filling errors, and programming errors have been reported and can be life threatening.
Increasing reports of catheter tip granuloma formation were thought to be the result of high drug concentrations. The exact drug concentration that will
predispose to granuloma formation is unknown
[7,12,13,23,57].
Efficacy of IDD for Chronic Pain
There is only one prospective randomized controlled
trial on IDD, in which 202 cancer patients with uncontrolled pain were randomized to either IDD or comprehensive medical management (CMM). Clinical success
was defined as at least 20% reduction in visual analogue
scale (VAS) scores or equal scores with at least 20% reduction in toxicity. More IDD patients achieved success
(84.5% vs. 70.8%; P = 0.05). More IDD patients achieved
at least 20% reduction in both pain VAS and toxicity.
There was a nonsignificant change in mean VAS between groups (IDD 52%, CMM 39%). IDD patients had
a significantly greater change in toxicity scores (52% vs.
17%; P = 0.004). There was no difference in survival between the groups [45].
Nonpharmacological Treatments
Hypnosis
Hypnosis has been used for centuries to treat pain
by generating a state of highly focused attention that
results in a dissociation from the pain [46,47]. It can
reduce pain and anxiety related to pain in both adults
and children [5,29].
Acupuncture
Acupuncture originated in China over 4000 years ago. Its
traditional basis hinges on the existence of acupuncture
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points; however, studies have found a greater than 70%
correlation between myofascial trigger points, motor
points, and acupuncture points [33,36]. In addition, the
traditional meridians in the extremities highly resemble
the distribution of peripheral nerves. The mechanism is
not clear, but acupuncture appears to work peripherally
by stimulating Aδ afferents and centrally through the
endorphin system [17,30]. There is also evidence of a
neurohumoral effect [26]. One animal study suggested
a long-term effect on neuroplasticity in rats with neuropathic pain [56]. There are two clinical trials showing
benefits of acupuncture in painful diabetic peripheral
neuropathy [1,21].
Transcutaneous Electrical Nerve Stimulation
TENS is a widely used treatment for chronic pain. An
estimated 250,000 units are prescribed annually in the
United States. There are two main stimulation patterns: (1) a low-frequency, 1–4-Hz, long-pulse-width,
high-intensity stimulation that causes muscle contraction; (2) a high-frequency 50–120-Hz, low-intensity
stimulation. The low-frequency pattern mimics acupuncture, whereas the high frequency uses the gate
control theory. The evidence is poor in supporting the
efficacy of TENS.
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
Abuaisha BB, Costanzi JB, Boulton AJM. Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long term
study. Diabetic Res Clin Pract 1998;39:115–21.
Armon C, Argoff CE, Samuels J, Backonja MM. Assessment: use of
epidural steroid injections to treat radicular lumbosacral pain: report
of the Therapeutics and Technology Assessment Subcommittee of the
American Academy of Neurology. Neurology 2007;68:723–9.
Bhadra N, Kilgore KL. High-frequency electrical conduction block of
mammalian peripheral motor nerve. Muscle Nerve 2005;32:782–90.
Brandwin MA, Kewman DG. MMPI indicators of treatment response
to spinal epidural stimulation in patients with chronic pain and patients
with movement disorders. Psychol Rep 1982;51:1059–64.
Butler LD, Symons BK, Henderson SL, Shortliffe LD, Spiegel D. Hypnosis reduces distress and duration of an invasive medical procedure for
children. Pediatrics 2005;115:e77–85.
Chung JM, Lee KH, Hori Y, Endo K, Willis WD. Factors influencing
peripheral nerve stimulation produced inhibition of primate spinothalamic tract cells. Pain 1984;19:277–93.
Coffey RJ, Burchiel K. Inflammatory mass lesions associated with intrathecal drug infusion catheters: report and observations on 41 patients.
Neurosurgery 2002;50:78–87.
Deer TR, Levy RM, Rosenfeld EL. Prospective clinical study of a new
implantable peripheral nerve stimulation device to treat chronic pain.
Clin J Pain 2010;26:359–72.
Deer TR, Prager J, Levy R, Burton A, Buschser E, Caraway D, Cousins
M, De Andres J, Diwan S, Erdek M, Grigsby E, Huntoon M, Jacobs M,
Kim P, Kumar K, Leong M, Liem L, McDowell G, Panchal SJ, Rauck
R, Saulino M, Staats P, Stanton-Hicks M, Stearns L, Sitzman BT, Wallace M, Willis K, Witt W, Yaksh T, Mekhail N. Polyanalgesic Consensus
Conference 2012: recommendations on trialing for intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation 2012;15:420–35.
254
[10] Deer TR, Prager J, Levy R, Burton A, Buschser E, Caraway D, Cousins
M, De Andres J, Diwan S, Erdek M, Grigsby E, Huntoon M, Jacobs M,
Kim P, Kumar K, Leong M, Liem L, McDowell G, Panchal SJ, Rauck
R, Saulino M, Staats P, Stanton-Hicks M, Stearns L, Sitzman BT, Wallace M, Willis K, Witt W, Yaksh T, Mekhail N. Polyanalgesic Consensus
Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation 2012;15:436–66.
[11] Deer TR, Smith HS, Burton AW, Pope JE, Doleys DM, Levy RM, Staats
PS, Wallace M, Webster LR, Rauck R, Cousins M. Comprehensive consensus based guidelines on intrathecal drug delivery systems in the treatment of pain caused by cancer pain. Pain Physician 2011;14:E283–312.
[12] Deer TR, Prager J, Levy R, Burton A, Buschser E, Caraway D, Cousins
M, De Andres J, Diwan S, Erdek M, Grigsby E, Huntoon M, Jacobs M,
Kim P, Kumar K, Leong M, Liem L, McDowell G, Panchal SJ, Rauck
R, Saulino M, Staats P, Stanton-Hicks M, Stearns L, Sitzman BT, Wallace M, Willis K, Witt W, Yaksh T, Mekhail N. Polyanalgesic Consensus
Conference 2012: recommendations to reduce morbidity and mortality in intrathecal (intraspinal) drug delivery in the treatment of chronic
pain. Neuromodulation 2012;15:467–82.
[13] Deer TR, Prager J, Levy R, Burton A, Buschser E, Caraway D, Cousins
M, De Andres J, Diwan S, Erdek M, Grigsby E, Huntoon M, Jacobs M,
Kim P, Kumar K, Leong M, Liem L, McDowell G, Panchal SJ, Rauck
R, Saulino M, Staats P, Stanton-Hicks M, Stearns L, Sitzman BT, Wallace M, Willis K, Witt W, Yaksh T, Mekhail N. Polyanalgesic Consensus Conference 2012: consensus on diagnosis, detection and treatment
of catheter tip granulomas (inflammatory masses). Neuromodulation
2012;15:483–96.
[14] De Ridder D, Vanneste S, Plazier M, van der Loo E, Menovsky T. Burst
spinal cord stimulation: Toward paresthesia-free pain suppression.
Neurosurgery 2010;66:986–90.
[15] De Ridder D, Vanneste S, van der Loo E, Plazier M, Menovsky T, van
de Heyning P. Burst stimulation of the auditory cortex: a new form
of neurostimulation for noise-like tinnitus suppression. J Neurosurg
2010;112:1289–94.
[16] Dworkin RH, O’Connor AB, Kent J, Mackey SC, Raja SN, Stacey BR,
Levy RM, Backonja M, Baron R, Harke H, Loeser JD, Treede RD, Turk
DC, Wells CD. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain 2013;154:2249–61.
[17] Fei H, Xie GX, Han JS. Differential release of met-enkephalin and dynorphin in spinal cord by electroacupuncture of different frequencies.
Kexue Tongbo 1986;31:1512–5.
[18] Field MJ, Lohr KN, editors. Committee to advise the public health service on clinical practice guidelines, Institute of Medicine. Washington,
DC: National Academy Press; 1990.
[19] Furnish T, Wallace M. Intrathecal drug delivery: patient selection, trialing, and implantation. In: Benzon H et al., editors. Practical management of pain. Philadelphia: Elsevier; 2013. p. 953–65.
[20] Graham R, Mancher M, Wolman DM, editors. Committee on Standards for developing trustworthy clinical practice guidelines; Institute
of Medicine. Washington, DC: National Academy Press; 1990.
[21] Hamza MA, Proctor TJ, White PF, Craig WF, Ghoname ES, Ahmed
HE, Proctor TJ, Noe CE, Vakharia AS, Gajraj N. Percutaneous electrical nerve stimulation: a novel analgesic therapy for diabetic neuropathic pain. Diabetes Care 2000;23:365–70.
[22] Harvey A, Swadlow I, Alexander G. The impact of “bursting” thalamic
impulses at the neocortical synapse. Nat Neurosci 2001;4:402–8.
[23] Hassenbusch S, Burchiel K, Coffey RJ, Cousins MJ, Deer T, Hahn MB,
Du Pen S, Follett KA, Krames E, Rogers JN, Sagher O, Staats PS, Wallace MS, Willis KD. Management of intrathecal catheter-tip inflammatory masses: a consensus statement. Pain Med 2002;3:31323.
[24] Hassenbusch SJ, Portenoy RK. Current practices in intraspinal therapy:
a survey of clinical trends and decision making. J Pain Symptom Manage 2000;20:S4–11.
[25] Jahnsen H, Llinas R. Voltage-dependent burst-to-tonic switching of
thalamic cell activity: an in vitro study. Arch Ital Biol 1984;122:73–82.
[26] Kaada B, Eielsen O. In search of mediators of skin vasodilation induced
by transcutaneous nerve stimulation: II. Serotonin implicated. Gen
Pharmacol 1983;14:635–41.
[27] Kemler MA, Barendse GAM, van Kleef M, de Vet HC, Rijks CP, Furnee
CA, van den Wildenberg FA. Spinal cord stimulation in patients with
chronic reflex sympathetic dystrophy. N Engl J Med 2000;343:618.
[28] Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, Thomson S, O’Callaghan J, Eisenberg E, Milbouw G, Buchser E, Fortini G,
Richardson J, North RB. Spinal cord stimulation versus conventional
medical management for neuropathic pain: a multicentre randomised
controlled trial in patients with failed back surgery syndrome. Pain
2007;132:179.
Mark S. Wallace
[29] Lang E, Benotsch E, Fink L, Lutgendorf S, Berbaum ML, Berbaum KS,
Logan H, Spiegel D. Adjunctive non-pharmacological analgesia for invasive medical procedures: a randomized trial. Lancet 2000;355:1486–90.
[30] Leung AY, Kim SJ, Schulteis G, Yaksh T. The effect of acupuncture duration on analgesia and peripheral sensory thresholds. BMC Complement Altern Med 2008;8:18.
[31] Liem L, Russo M, Huygen FJ, van Buyten JP, Smet I, Verrillis P, Cousins
M, Brooker C, Levy R, Deer T, Kramer J. A multicenter, prospective trial to assess the safety and performance of the spinal modulation dorsal
root ganglion neurostimulator system in the treatment of chronic pain.
Neuromodulation 2013;16:471–82.
[32] Linderoth B, Meyerson BA. Spinal cord stimulation, I. Mechanisms of
action. In: Burchiel K, editor. Pain surgery. New York: Thieme; 1999.
[33] Liu Y, Varela M, Oswald R. The correspondence between some motor
points and acupuncture loci. Am J Chin Med 1975;3:347–58.
[34] Lopez-Garcia JA, King AE. Membrane properties of physiologically
classified rat dorsal horn neurons in vitro: correlation with cutaneous
sensory afferent input. Eur J Neurosci 1994;6:998–1007.
[35] Manchikanti L, Falco FJE, Singh V, Benyamin RM, Racz, GB, Helm
S, Caraway DL, Calodney AK, Snook LT, Smith HS, Gupta S, Ward
SP, Grider JS, Hirsh JA. An update of comprehensive evidence-based
guidelines for interventional techniques in chronic spinal pain. Part I:
Introduction and general considerations. Pain Physician 2013;16:S1–48.
[36] Melzack R, Stillwell DM, Fox EJ. Trigger points and acupuncture points
for pain: correlations and implications. Pain 1977;3:3–23.
[37] Melzack R, Wall PD. Pain mechanisms: a new theory. Science
1965;150:971.
[38] North RB, Kidd D, Shipley J, Taylor R. Spinal cord stimulation versus
reoperation for failed back surgery syndrome: A cost effectiveness and
cost utility analysis based on a randomized, controlled trial. Neurosurgery 2007;61:361.
[39] Oakley J, Staats P. The use of implanted drug delivery systems. In: Raj
PP, editor. The practical management of pain. St Louis; Mosby: 2000. p.
768–78.
[40] Paice JA, Penn RD, Shott S. Intraspinal morphine for chronic pain: a retrospective, multicenter study. J Pain Symptom Manage 1996;11:71–80.
[41] Perruchoud C, Eldabe S, Batterham AM, Madzinga G, Brookes M,
Durrer A, Rosato M, Bovet N, West S, Bovy M, Rutschman B, Gulve
A, Garner F, Buchser E. Analgesic efficacy of high-frequency spinal
cord stimulation: a randomized, double-blind placebo-controlled study.
Neuromodulation 2013;16:363–9.
[42] Rauck RL, Wallace MS, Leong MS, MineHart M, Webster LR,
Charapata SG, Abraham JE, Buffington DE, Ellis D, Kartzinel R, Ziconotide 301 Study Group. A randomized, double-blind, placebocontrolled study of intrathecal ziconotide in adults with severe chronic
pain. J Pain Symptom Manage 2006;31:393–406.
[43] Scanlon GC, Moeller-Bertram T, Romanowsky SM, Wallace MS. Cervical transforaminal epidural steroid injections: more dangerous than
we think? Spine 2007;32:1249–56.
[44] Silberstein SD, Dodick DW, Saper J, Huh B, Slavin KV, Sharan A, Reed
K, Narouze S, Mogilner A, Goldstein J, Trentman T, Vaisma J, Ordia
J, Weber P, Deer T, Levy R, Diaz RL, Washburn SN, Mekhail N. Safety
and efficacy of peripheral nerve stimulation of the occipital nerves for
the management of chronic migraine: results from a randomized, multicenter, double-blinded, controlled study. Cephalalgia 2012;32:1165–
79.
[45] Smith TJ, Staats PS, Deer T, Stearns LJ, Rauck RL, Boortz-Marx RL,
Buchser E, Català E, Bryce DA, Coyne PJ, Pool GE; Implantable Drug
Delivery Systems Study Group. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol 2002;20:4040–9.
[46] Spiegel D. The mind prepared: hypnosis for surgery. J Natl Cancer Inst
2007;99:1280–1.
[47] Spiegel H, Spiegel D. Trance and treatment: clinical uses of hypnosis.
Washington, DC: American Psychiatric Press; 2004.
[48] Staats PS, Yearwood T, Charapata SG, Presley RW, Wallace MS, ByasSmith M, Fisher R, Bryce DA, Mangieri EA, Luther RR, Mayo M, McGuire D. Intrathecal ziconotide in the treatment of refractory pain in
patients with cancer and AIDS: a randomized controlled trial. JAMA
2004;291:63–70.
[49] Tiede J, Brown L, Gekht G, Vallejo R, Yearwood T, Morgan D. Novel
spinal cord stimulation parameters in patients with predominant back
pain. Neuromodulation 2013;16:370–5.
[50] Van Buyten J-P, Al-Kaisy A, Smet I, Palmisani S, Smith T. High-frequency spinal cord stimulation for the treatment of chronic back pain
patients: results of a prospective multicenter European clinical study.
Neuromodulation 2013;16:59–66.
Interventional and Nondrug Neuropathic Pain Therapies
[51] Wall PD, Gutnick M. Properties of afferent nerve impulses originating
from a neuroma. Nature 1974;248:740–3.
[52] Wall PD, Sweet WH. Temporary abolition of pain in man. Science
1967;155:108–9.
[53] Wallace MS, Charpata SG, Fisher R, Byas-Smith M, Staats PS, Mayo
M, McGuire D, Ellis D; Ziconotide Nonmalignant Pain Study 96-002
Group. Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a randomized, double-blind, placebo-controlled clinical trial.
Neuromodulation 2006;9:75–86.
[54] Wallace MS, Rauck RL, Deer T. Ziconotide combination intrathecal
therapy: rationale and evidence. Clin J Pain 2010;26:635–44.
[55] Wallace MS, Yaksh TL. Long-term intraspinal drug therapy: a review.
Reg Anesth Pain Med 2000;25:117–57.
255
[56] Xing GG, Liu FY, Qu XX, Han JS, Wan Y. Long term synaptic plasticity
in the dorsal horn neuron and its modulation by electroacupuncture in
rats with neuropathic pain. Exp Neurol 2007; 208:323–32.
[57] Yaksh TL, Hassenbusch SJ, Burchiel K. Inflammatory masses associated with intrathecal drug infusion: a review of preclinical evidence and
human data. Pain Med 2002;3:300–12.
Correspondence to: Professor Mark S. Wallace, MD, Department of Clinical Anesthesiology, University of California, San
Diego, 9300 Campus Point Drive, #7651, La Jolla, CA 92037,
USA. Email: mswallace@ucsd.edu.