Treating Phantom Limb Pain Using Continuous Peripheral Nerve Blocks: A Department of Defense Funded Multicenter Study
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/16/2019 |
| Start Date: | December 1, 2013 |
| End Date: | October 2019 |
Treating Intractable Post-Amputation Phantom Limb Pain With Ambulatory Continuous Peripheral Nerve Blocks
When a limb is traumatically severed, pain perceived in the part of the body that no longer
exists often develops. This is called "phantom limb" pain, and is different from "stump"
pain, which is pain within the part of the limb that remains intact. Unfortunately, phantom
pain resolves in only 16% of people, with the rest experiencing this pain for the remainder
of the lives. There is currently no reliable treatment for phantom limb pain.
The exact reason that phantom limb pain occurs is unclear, but when a nerve is cut—as happens
with a traumatic amputation—changes occur in the brain and spinal cord that actually worsen
with increasing phantom pain. These abnormal changes may often be corrected by putting local
anesthetic—termed a "peripheral nerve block"—on the injured nerve, keeping any "bad signals"
from reaching the brain, with resolution of the phantom limb pain. However, when the nerve
block ends after a few hours, the phantom pain returns. But, this demonstrates that the brain
abnormalities—and phantom pain—that occur with an amputation may be dependent upon the "bad"
signals being sent from the injured nerve(s), suggesting that a very long peripheral nerve
block—lasting many days rather than hours—may permanently reverse the abnormal changes in the
brain, and provide lasting relief from phantom pain.
Until recently, extending a peripheral nerve block beyond 16 hours was unrealistic. However,
a treatment option called a "continuous peripheral nerve block" is now available. This
technique involves the placement of a tiny tube—smaller than a piece of spaghetti—through the
skin and next to the nerves supplying the amputated limb. The tiny tube may be placed with
minimal discomfort in about 15 minutes. Numbing medicine called local anesthetic is then
infused through the tube, blocking any signals that the injured nerve sends to the spinal
cord and brain. Using a small, portable infusion pump, this prolonged nerve block may be
provided in individuals' own homes.
The ultimate objective of the proposed research study is to determine if a 6-day continuous
peripheral nerve block provided at home is an effective treatment for persistent phantom limb
pain following a traumatic limb amputation. The primary hypothesis (what the researchers
predict) is that phantom limb pain intensity will be significantly decreased 4 weeks
following treatment with a 6-day continuous peripheral nerve block.
exists often develops. This is called "phantom limb" pain, and is different from "stump"
pain, which is pain within the part of the limb that remains intact. Unfortunately, phantom
pain resolves in only 16% of people, with the rest experiencing this pain for the remainder
of the lives. There is currently no reliable treatment for phantom limb pain.
The exact reason that phantom limb pain occurs is unclear, but when a nerve is cut—as happens
with a traumatic amputation—changes occur in the brain and spinal cord that actually worsen
with increasing phantom pain. These abnormal changes may often be corrected by putting local
anesthetic—termed a "peripheral nerve block"—on the injured nerve, keeping any "bad signals"
from reaching the brain, with resolution of the phantom limb pain. However, when the nerve
block ends after a few hours, the phantom pain returns. But, this demonstrates that the brain
abnormalities—and phantom pain—that occur with an amputation may be dependent upon the "bad"
signals being sent from the injured nerve(s), suggesting that a very long peripheral nerve
block—lasting many days rather than hours—may permanently reverse the abnormal changes in the
brain, and provide lasting relief from phantom pain.
Until recently, extending a peripheral nerve block beyond 16 hours was unrealistic. However,
a treatment option called a "continuous peripheral nerve block" is now available. This
technique involves the placement of a tiny tube—smaller than a piece of spaghetti—through the
skin and next to the nerves supplying the amputated limb. The tiny tube may be placed with
minimal discomfort in about 15 minutes. Numbing medicine called local anesthetic is then
infused through the tube, blocking any signals that the injured nerve sends to the spinal
cord and brain. Using a small, portable infusion pump, this prolonged nerve block may be
provided in individuals' own homes.
The ultimate objective of the proposed research study is to determine if a 6-day continuous
peripheral nerve block provided at home is an effective treatment for persistent phantom limb
pain following a traumatic limb amputation. The primary hypothesis (what the researchers
predict) is that phantom limb pain intensity will be significantly decreased 4 weeks
following treatment with a 6-day continuous peripheral nerve block.
Background. The combination of increased munitions force, use of improvised explosive
devices, and casualty survival rates has resulted in a dramatic increase in the percentage of
injured combat veterans living with a traumatic amputation. Of American Veteran amputees,
35-98% develop chronic, intractable pain perceived as being from the missing limb, a
phenomenon termed "phantom limb pain." This pain resolves in only 16% of afflicted
individuals, and there is currently no reliable treatment. The etiology of phantom pain
remains unclear, but evidence suggests that severing a nerve provokes changes in the spinal
cord, thalamus, and cerebral cortex. When neural input from an amputated limb is blocked with
local anesthetic (a peripheral nerve block), cortical abnormalities and phantom pain
frequently resolve. However, when the single-injection nerve block resolves after a few
hours, the phantom pain returns. These findings demonstrate that cortical abnormalities and
phantom pain may be maintained from abnormal peripheral input, suggesting that a peripheral
nerve block of extended duration—lasting many days rather than hours—may permanently
reorganize cortical pain mapping, thus providing lasting relief from phantom pain. A
"continuous peripheral nerve block" (CPNB) involves the percutaneous insertion of a catheter
directly adjacent to the peripheral nerves supplying an affected limb. Local anesthetic
infused via the catheter(s) induces a completely insensate extremity for as long as desired
without any systemic side effects. Additionally, CPNB may be provided on an ambulatory basis
using a small, portable pump to infuse the local anesthetic.
Objective. To determine if ambulatory CPNB is an effective treatment for intractable phantom
limb pain following a traumatic limb amputation. Previously-published small, uncontrolled
series describe patients immediately following surgical amputation whose phantom limb pain
dramatically decreased or completely resolved with CPNB. We have data from a randomized,
double-masked, placebo-controlled, crossover pilot study suggesting great promise treating
intractable phantom limb pain with ambulatory CPNB: participants (n=3) experienced no change
in their phantom pain following a 6-day infusion of normal saline; however, with a 6-day CPNB
of potent local anesthetic administered 4 months later, subjects (n=2; one patient returned
to duty before crossover infusion) experienced complete resolution of their phantom limb
pain. Within the 12-week follow-up period, one subject experienced no phantom pain
recurrence; and the other subject reported mild pain occurring once each week of just a small
fraction of his original pain.
Specific Aims. The primary hypothesis is that phantom limb pain intensity will be
significantly decreased 4 weeks following an ambulatory CPNB (as measured by the Numeric
Rating Scale of the Brief Pain Inventory).
Study Design. We propose a multicenter, randomized, double-masked, placebo-controlled,
simultaneous parallel and crossover, human-subjects clinical trial. We will include subjects
with an existing upper or lower amputation who experience phantom limb pain at least daily
for the previous 4 weeks. Catheter site(s) will be determined by amputation location.
Subjects will be randomized to receive one of two study solutions in a double-masked manner:
either a local anesthetic (ropivacaine 0.5%) or placebo (normal saline). Catheters will be
removed after 6 days of at-home infusion. Although not required, each subject has the option
to return for the alternative treatment four weeks later (crossover infusion). The primary
endpoint will be the difference in average phantom pain intensity at baseline and 4 weeks
following the initial infusion as measured with the Numeric Rating Scale between treatment
groups for the initial infusion. Major secondary endpoints will involve intra- and
inter-subject comparisons of additional measures of pain and health-related quality-of-life.
Clinical Impact. From 2001-2006, over 70% of all U.S. military casualties endured a major
limb injury, with an amputation rate of 28% within Operation Enduring Freedom alone. Previous
conflicts have left tens-of-thousands of United States Armed Forces Veterans with missing
limbs. CPNB are now relatively ubiquitous within the United States, but applied nearly
exclusively to provide acute post-injury/surgical analgesia. If the proposed study
demonstrates that ambulatory CPNB is a reliable treatment for intractable phantom limb pain,
the resulting impact in treating the consequences of traumatic amputation will be immediate
and profound, as healthcare providers within the United States Armed Forces and Veterans
Affairs Medical Centers already have expertise placing and managing perineural catheters.
Currently, CPNB is provided exclusively in the acute setting—to treat pain immediately
following a battlefield injury or surgery—and not chronic, intractable phantom limb pain.
However, because there is little technical difference in providing CPNB for acute versus
chronic pain, the thousands of U.S. Veterans and active duty personnel suffering from
intractable phantom pain could be treated relatively easily, rapidly, and with negligible
additional costs.
devices, and casualty survival rates has resulted in a dramatic increase in the percentage of
injured combat veterans living with a traumatic amputation. Of American Veteran amputees,
35-98% develop chronic, intractable pain perceived as being from the missing limb, a
phenomenon termed "phantom limb pain." This pain resolves in only 16% of afflicted
individuals, and there is currently no reliable treatment. The etiology of phantom pain
remains unclear, but evidence suggests that severing a nerve provokes changes in the spinal
cord, thalamus, and cerebral cortex. When neural input from an amputated limb is blocked with
local anesthetic (a peripheral nerve block), cortical abnormalities and phantom pain
frequently resolve. However, when the single-injection nerve block resolves after a few
hours, the phantom pain returns. These findings demonstrate that cortical abnormalities and
phantom pain may be maintained from abnormal peripheral input, suggesting that a peripheral
nerve block of extended duration—lasting many days rather than hours—may permanently
reorganize cortical pain mapping, thus providing lasting relief from phantom pain. A
"continuous peripheral nerve block" (CPNB) involves the percutaneous insertion of a catheter
directly adjacent to the peripheral nerves supplying an affected limb. Local anesthetic
infused via the catheter(s) induces a completely insensate extremity for as long as desired
without any systemic side effects. Additionally, CPNB may be provided on an ambulatory basis
using a small, portable pump to infuse the local anesthetic.
Objective. To determine if ambulatory CPNB is an effective treatment for intractable phantom
limb pain following a traumatic limb amputation. Previously-published small, uncontrolled
series describe patients immediately following surgical amputation whose phantom limb pain
dramatically decreased or completely resolved with CPNB. We have data from a randomized,
double-masked, placebo-controlled, crossover pilot study suggesting great promise treating
intractable phantom limb pain with ambulatory CPNB: participants (n=3) experienced no change
in their phantom pain following a 6-day infusion of normal saline; however, with a 6-day CPNB
of potent local anesthetic administered 4 months later, subjects (n=2; one patient returned
to duty before crossover infusion) experienced complete resolution of their phantom limb
pain. Within the 12-week follow-up period, one subject experienced no phantom pain
recurrence; and the other subject reported mild pain occurring once each week of just a small
fraction of his original pain.
Specific Aims. The primary hypothesis is that phantom limb pain intensity will be
significantly decreased 4 weeks following an ambulatory CPNB (as measured by the Numeric
Rating Scale of the Brief Pain Inventory).
Study Design. We propose a multicenter, randomized, double-masked, placebo-controlled,
simultaneous parallel and crossover, human-subjects clinical trial. We will include subjects
with an existing upper or lower amputation who experience phantom limb pain at least daily
for the previous 4 weeks. Catheter site(s) will be determined by amputation location.
Subjects will be randomized to receive one of two study solutions in a double-masked manner:
either a local anesthetic (ropivacaine 0.5%) or placebo (normal saline). Catheters will be
removed after 6 days of at-home infusion. Although not required, each subject has the option
to return for the alternative treatment four weeks later (crossover infusion). The primary
endpoint will be the difference in average phantom pain intensity at baseline and 4 weeks
following the initial infusion as measured with the Numeric Rating Scale between treatment
groups for the initial infusion. Major secondary endpoints will involve intra- and
inter-subject comparisons of additional measures of pain and health-related quality-of-life.
Clinical Impact. From 2001-2006, over 70% of all U.S. military casualties endured a major
limb injury, with an amputation rate of 28% within Operation Enduring Freedom alone. Previous
conflicts have left tens-of-thousands of United States Armed Forces Veterans with missing
limbs. CPNB are now relatively ubiquitous within the United States, but applied nearly
exclusively to provide acute post-injury/surgical analgesia. If the proposed study
demonstrates that ambulatory CPNB is a reliable treatment for intractable phantom limb pain,
the resulting impact in treating the consequences of traumatic amputation will be immediate
and profound, as healthcare providers within the United States Armed Forces and Veterans
Affairs Medical Centers already have expertise placing and managing perineural catheters.
Currently, CPNB is provided exclusively in the acute setting—to treat pain immediately
following a battlefield injury or surgery—and not chronic, intractable phantom limb pain.
However, because there is little technical difference in providing CPNB for acute versus
chronic pain, the thousands of U.S. Veterans and active duty personnel suffering from
intractable phantom pain could be treated relatively easily, rapidly, and with negligible
additional costs.
Inclusion Criteria:
- 18 years of age or older
- Upper or lower limb traumatic or surgical amputation at least 12 weeks prior to
enrollment at or distal to the mid-humerus or hip (femoral head remaining),
respectively; and including at least one metacarpal or metatarsal bone, respectively.
- Experiencing at least moderate phantom limb pain (defined as 2 or higher on the
numeric rating scale, NRS 0-10), at least three times each week for the previous 8
weeks.
- Accepting of an ambulatory continuous peripheral nerve block for 6 days.
- Willing to avoid changes to their analgesic regimen from 4 weeks prior to and at least
4 weeks following the initial catheter placement (preferably 4 weeks following the
second/crossover catheter insertion as well).
- Having a "caretaker" who will transport the subject home following the catheter
insertion(s), and remain with the subject for the first night of the infusions.
Exclusion Criteria:
- Known renal insufficiency
- Allergy to study medications
- Pregnancy
- Incarceration
- Inability to communicate with the investigators
- Morbid obesity (BMI greater than 40)
- Comorbidity that results in moderate-to-severe functional limitation (ASA greater than
2)
- Possessing any contraindication to ambulatory perineural catheter placement or
perineural local anesthetic infusion:
- Current infection
- Immune-compromised status of any etiology
- Uncontrolled anxiety/panic disorder
- Inability to contact investigators during the perineural infusion
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