Treatments for Neuropathy
Drug Therapy
Unfortunately, many drugs used to treat neuropathy have side effects that, in some cases, are
worse then the neuropathy symptoms themselves. Also, to my knowledge, none of the
available prescription medications actually address the causative process, but rather trick the
brain and body into not feeling pain. Prescription pharmacologic therapies for neuropathies
include antidepressants like selective serotonin reuptake inhibitors (SSRIs), serotonin and
norepinephrine reuptake inhibitors (SNRIs), dopamine-agonists (e.g., levodopa), analgesics
(e.g., tramadol) anticonvulsants and antiarrhythmics. Cymbalta® (duloxetine) and Lyrica®
(pregabalin) are FDA-approved for neuropathy.
Common side effects for Lyrica® include: dizziness, somnolence, impaired concentration,
blurred vision, weight gain and edema in >5% of patients (Source: Lyrica® prescribing
information).
Common side effects for Cymbalta® include: major depressive episode, generalized anxiety,
fibromyalgia symptoms including fatigue, nausea, dry mouth, constipation, somnolence,
hyperhidrosis, and decreased appetite in >5% of patients (Source: Cymbalta® prescribing
information).
Other Treatments
As most people with diabetes are on many medications, non-prescription treatment options
are preferred whenever possible. Fortunately, for neuropathy, there are several safe options,
many of which have an evidence-base grounded in human clinical trials.
Topical Capsaicin Cream (Zostrix®)
Zostrix® is a 0.075% capsaicin cream can be applied topically for pain relief in both arthritis
and diabetic peripheral neuropathy. Capsaicin depletes Substance P, the chemical
messenger that facilitates the sensory perception of pain at the nerve ending. It is important to
note that capsaicin does not change the course of neuropathy, but only masks the pain.
Because it takes up to a week or more to deplete Substance P, and because capsaicin does
stimulate local burning, you have to stick with it for several weeks (and tolerate some
discomfort) before it is effective.
Capsaicin
Contrary to all drugs described which are used systemically and therefore lead to
systemic side effects, capsaicin, a chili pepper ingredient, topically applied four times
daily as a 0.075% cream, may reduce neuropathic pain in diabetic patients. The NNT
is 3–5, the NNH is 2–3 [14]. The effect achieved is comparable with that of
amitripyline [15]. The high rate of adverse events is caused by the initially increased
pain sensation in the creamed areas, the unintentional contamination of mucous
membranes like conjunctivae, and the inhalation of dried cream particles. Systemic
adverse events do not occur although long term toxic effects on nerve endings are not
yet totally excluded.
What research has been done on capsaicin cream?
Thirteen out of 16 randomized controlled trials involving a total of 1535 people found
capsaicin was more effective than placebo.

Arthritis - Researchers with Case Western Reserve University examined the
use of capsaicin cream in 70 patients with osteoarthritis and 31 with
rheumatoid arthritis. After 4 weeks of applying a 0.025% capsaicin cream or
placebo to painful knees, the capsaicin patients had significantly more pain
relief. Rheumatoid arthritis patients had 57% pain reduction and osteoarthritis
patients had 33% pain reduction-both were considered more effective than
placebo.
A European Journal of Pain study found that osteoarthritis pain was reduced
after 6 weeks of using a 0.025% capsaicin cream.

Back Pain - A German study compared a capsaicin plaster with a placebo for
3 weeks in 154 patients with chronic back pain. After 3 weeks, 60.8% of
patients in the capsaicin group experienced at least a 30% reduction in pain,
compared to 42.1% in the placebo group.

Nerve Pain - A British Journal of Pharmacology study assessed the
effectiveness of the topical pain-relieving medication doxepin, a 0.025%
capsaicin cream, a combination, or a placebo in 200 patients with chronic
nerve pain. After 4 weeks, all three treatments significantly reduced pain.
A study by researchers with the Geisinger Clinical Oncology Program found
that cancer patients with post-surgical nerve pain had substantially more pain
relief after using capsaicin cream, with an average pain reduction of 53%
versus 17% for the placebo.
Researchers with the University of Toronto evaluated the effectiveness of
0.075% capsaicin cream or placebo in 143 patients with post-herpetic
neuralgia. After 6 weeks, those using the capsaicin cream had a significant
reduction in pain. In contrast, patients using the placebo cream remained
unchanged. A 2 year follow-up found that the pain relief was maintained or
further improved in 86%.
At least 5 randomized controlled trials have found that 0.075% capsaicin
cream is more effective than a placebo in relieving pain associated with
diabetic neuropathy. An 8-week multicenter study of 235 patients with
diabetic neuropathy involving the feet found that they were both equally
effective in reducing pain. However, the capsaicin cream didn't have systemic
side effects (such as drowsiness or cardiovascular side effects) prompting
researchers to conclude that it may be a safer option.

Pruritic Psoriasis - A study by the University of Michigan Medical School
examined the safety and efficacy of 0.025% capsaicin cream versus placebo
in patients with pruritic (itchy) psoriasis. After 6 weeks, capsaicin patients had
significantly greater improvement in itching.
Common Doses
A recommended starting dose is 0.025% capsaicin cream applied four times a day. If this
dose is ineffective, a 0.075% capsaicin cream can be used under the guidance of a health
practitioner. Capsaicin cream is applied directly over areas of muscle or joint pain or
itching.
Capsaicin cream can cause a stinging or burning sensation on the skin. Not everyone
experiences it and the sensation doesn't appear to be necessary for it to work.
Some practitioners recommend using capsaicin cream for at least 4 continuous weeks to
evaluate the effectiveness.
Safety




Wear gloves when applying capsaicin cream.
Do not apply it immediately after a hot bath or shower or use it with a heating
pad.
Avoid getting capsaicin cream in eyes and other mucus membranes or broken
skin.
The safety of capsaicin cream in pregnant or nursing women hasn't been
established.
Side Effects
The main side effect of using capsaicin cream is that it can cause an uncomfortable
burning sensation in the area.
Other side effects are coughing and skin redness. Higher doses can cause pain,
inflammation, and skin blisters.
Drug Interactions
There have been no reported drug interactions with topical capsaicin cream.
Capsaicin Cream is used for:
Temporary relief of muscle and joint pain associated with arthritis,
simple backaches, sprains, strains, and bruises. It may also be used
for other conditions as determined by your doctor.
Capsaicin Cream is a topical analgesic. Exactly how it works is
unknown, but it is thought to decrease the amount of a certain
substance (substance P) that transmits pain in the body.
Do NOT use Capsaicin Cream if:
you are allergic to any
ingredient in Capsaicin
Cream
Contact your doctor or health care provider right away if any of these
apply to you.
Before using Capsaicin Cream:
Some medical conditions may interact with Capsaicin Cream. Tell your
doctor or pharmacist if you have any medical conditions, especially if
any of the following apply to you:

if
yo
u
ar
e
pr
eg
na
nt,
pla
nn
in
g
to
be
co
m
e
pr
eg
na
nt,
or
ar
e
br
ea
stfee
di
ng

if
yo
u
ar
e
ta
ki
ng
an
y
pr
es
cri
pti
on
or
no
np
res
cri
pti
on
m
edi
cin
e,
he
rb
al
pr
ep
ar
ati
on
,
or
die
tar
y
su
pp
le
m
en
t

if
yo
u
ha
ve
all
er
gie
s
to
m
edi
cin
es,
fo
od
s,
or
ot
he
r
su
bs
ta
nc
es

if
yo
u
ha
ve
an
op
en
wo
un
d
or
da
m
ag
ed
,
br
ok
en
,
or
irri
tat
ed
ski
n
Some MEDICINES MAY INTERACT with Capsaicin Cream. Because little,
if any, of Capsaicin Cream is absorbed into the blood, the risk of it
interacting with another medicine is low.
Ask your health care provider if Capsaicin Cream may interact with
other medicines that you take. Check with your health care provider
before you start, stop, or change the dose of any medicine.
How are diabetic neuropathies treated?
The first treatment step is to bring blood glucose levels within the normal range to
help prevent further nerve damage. Blood glucose monitoring, meal planning,
physical activity, and diabetes medicines or insulin will help control blood glucose
levels. Symptoms may get worse when blood glucose is first brought under control,
but over time, maintaining lower blood glucose levels helps lessen symptoms. Good
blood glucose control may also help prevent or delay the onset of further problems.
As scientists learn more about the underlying causes of neuropathy, new treatments
may become available to help slow, prevent, or even reverse nerve damage.
As described in the following sections, additional treatment depends on the type of
nerve problem and symptom. If you have problems with your feet, your doctor may
refer you to a foot care specialist.
Pain Relief
Doctors usually treat painful diabetic neuropathy with oral medications, although
other types of treatments may help some people. People with severe nerve pain may
benefit from a combination of medications or treatments. Talk with your health care
provider about options for treating your neuropathy.
Medications used to help relieve diabetic nerve pain include




tricyclic antidepressants, such as amitriptyline, imipramine, and desipramine
(Norpramin, Pertofrane)
other types of antidepressants, such as duloxetine (Cymbalta), venlafaxine,
bupropion (Wellbutrin), paroxetine (Paxil), and citalopram (Celexa)
anticonvulsants, such as pregabalin (Lyrica), gabapentin (Gabarone,
Neurontin), carbamazepine, and lamotrigine (Lamictal)
opioids and opioid-like drugs, such as controlled-release oxycodone, an
opioid; and tramadol (Ultram), an opioid that also acts as an antidepressant
Duloxetine and pregabalin are approved by the U.S. Food and Drug Administration
specifically for treating painful diabetic peripheral neuropathy.
You do not have to be depressed for an antidepressant to help relieve your nerve pain.
All medications have side effects, and some are not recommended for use in older
adults or those with heart disease. Because over-the-counter pain medicines such as
acetaminophen and ibuprofen may not work well for treating most nerve pain and can
have serious side effects, some experts recommend avoiding these medications.
Treatments that are applied to the skin—typically to the feet—include capsaicin
cream and lidocaine patches (Lidoderm, Lidopain). Studies suggest that nitrate sprays
or patches for the feet may relieve pain. Studies of alpha-lipoic acid, an antioxidant,
and evening primrose oil have shown that they can help relieve symptoms and may
improve nerve function.
A device called a bed cradle can keep sheets and blankets from touching sensitive feet
and legs. Acupuncture, biofeedback, or physical therapy may help relieve pain in
some people. Treatments that involve electrical nerve stimulation, magnetic therapy,
and laser or light therapy may be helpful but need further study. Researchers are also
studying several new therapies in clinical trials.
Gastrointestinal Problems
To relieve mild symptoms of gastroparesis—indigestion, belching, nausea, or
vomiting—doctors suggest eating small, frequent meals; avoiding fats; and eating less
fiber. When symptoms are severe, doctors may prescribe erythromycin to speed
digestion, metoclopramide to speed digestion and help relieve nausea, or other
medications to help regulate digestion or reduce stomach acid secretion.
To relieve diarrhea or other bowel problems, doctors may prescribe an antibiotic such
as tetracycline, or other medications as appropriate.
Dizziness and Weakness
Sitting or standing slowly may help prevent the light-headedness, dizziness, or
fainting associated with blood pressure and circulation problems. Raising the head of
the bed or wearing elastic stockings may also help. Some people benefit from
increased salt in the diet and treatment with salt-retaining hormones. Others benefit
from high blood pressure medications. Physical therapy can help when muscle
weakness or loss of coordination is a problem.
Urinary and Sexual Problems
To clear up a urinary tract infection, the doctor will probably prescribe an antibiotic.
Drinking plenty of fluids will help prevent another infection. People who have
incontinence should try to urinate at regular intervals—every 3 hours, for example—
since they may not be able to tell when the bladder is full.
To treat erectile dysfunction in men, the doctor will first do tests to rule out a
hormonal cause. Several methods are available to treat erectile dysfunction caused by
neuropathy. Medicines are available to help men have and maintain erections by
increasing blood flow to the penis. Some are oral medications and others are injected
into the penis or inserted into the urethra at the tip of the penis. Mechanical vacuum
devices can also increase blood flow to the penis. Another option is to surgically
implant an inflatable or semirigid device in the penis.
Vaginal lubricants may be useful for women when neuropathy causes vaginal dryness.
To treat problems with arousal and orgasm, the doctor may refer women to a
gynecologist.
Foot Care
People with neuropathy need to take special care of their feet. The nerves to the feet
are the longest in the body and are the ones most often affected by neuropathy. Loss
of sensation in the feet means that sores or injuries may not be noticed and may
become ulcerated or infected. Circulation problems also increase the risk of foot
ulcers.
More than half of all lower-limb amputations in the United States occur in people
with diabetes—86,000 amputations per year. Doctors estimate that nearly half of the
amputations caused by neuropathy and poor circulation could have been prevented by
careful foot care.
Follow these steps to take care of your feet:









Clean your feet daily, using warm—not hot—water and a mild soap. Avoid
soaking your feet. Dry them with a soft towel and dry carefully between your
toes.
Inspect your feet and toes every day for cuts, blisters, redness, swelling,
calluses, or other problems. Use a mirror—laying a mirror on the floor works
well—or get help from someone else if you cannot see the bottoms of your
feet. Notify your health care provider of any problems.
Moisturize your feet with lotion, but avoid getting the lotion between your
toes.
After a bath or shower, file corns and calluses gently with a pumice stone.
Each week or when needed, cut your toenails to the shape of your toes and file
the edges with an emery board.
Always wear shoes or slippers to protect your feet from injuries. Prevent skin
irritation by wearing thick, soft, seamless socks.
Wear shoes that fit well and allow your toes to move. Break in new shoes
gradually by first wearing them for only an hour at a time.
Before putting your shoes on, look them over carefully and feel the insides
with your hand to make sure they have no tears, sharp edges, or objects in
them that might injure your feet.
If you need help taking care of your feet, make an appointment to see a foot
doctor, also called a podiatrist.
For additional information about foot care, contact the National Diabetes Information
Clearinghouse at 1–800–860–8747. See the publication Prevent diabetes problems:
Keep your feet and skin healthy at
www.diabetes.niddk.nih.gov/dm/pubs/complications_feet. Materials are also available
from the National Diabetes Education Program, including the fact sheet Take Care of
Your Feet for a Lifetime at www.ndep.nih.gov/campaigns/Feet/Feet_overview.htm.
[Top]
Points to Remember



Diabetic neuropathies are nerve disorders caused by many of the abnormalities
common to diabetes, such as high blood glucose.
Neuropathy can affect nerves throughout the body, causing numbness and
sometimes pain in the hands, arms, feet, or legs, and problems with the
digestive tract, heart, sex organs, and other body systems.
Treatment first involves bringing blood glucose levels within the normal
range. Good blood glucose control may help prevent or delay the onset of
further problems.



Foot care is an important part of treatment. People with neuropathy need to
inspect their feet daily for any injuries. Untreated injuries increase the risk of
infected foot sores and amputation.
Treatment also includes pain relief and other medications as needed,
depending on the type of nerve damage.
Smoking significantly increases the risk of foot problems and amputation. If
you smoke, ask your health care provider for help with quitting.
Pronunciation
(kap SAY sin)
U.S. Brand Names
ArthriCare® for Women Extra Moisturizing [OTC]; ArthriCare® for Women Multi-Action [OTC];
ArthriCare® for Women Silky Dry [OTC]; ArthriCare® for Women Ultra Strength [OTC];
Capsagel® [OTC]; Capzasin-HP® [OTC]; Capzasin-P® [OTC]; TheraPatch® Warm [OTC]
[DSC]; Zostrix® [OTC]; Zostrix®-HP [OTC]
Generic Available
Yes: Cream
Canadian Brand Names
Antiphogistine Rub A-535 Capsaicin; Zostrix®; Zostrix® H.P.
Use
Topical treatment of pain associated with postherpetic neuralgia, rheumatoid arthritis,
osteoarthritis, diabetic neuropathy; postsurgical pain
Use - Unlabeled/Investigational
Treatment of pain associated with psoriasis, chronic neuralgias unresponsive to other forms of
therapy, and intractable pruritus
Pregnancy Risk Factor
C
Contraindications
Hypersensitivity to capsaicin or any component of the formulation
Warnings/Precautions
Should not be applied to broken or irritated skin. Affected area should not be tightly bandaged.
Adverse Reactions
Frequency not defined.
Dermatologic: Itching, stinging sensation, erythema
Local: Transient burning on application which usually diminishes with repeated use
Respiratory: Cough
Drug Interactions
Substrate of CYP2E1 (minor)
No drug interaction data reported
Mechanism of Action
Induces release of substance P, the principal chemomediator of pain impulses from the
periphery to the CNS, from peripheral sensory neurons; after repeated application, capsaicin
depletes the neuron of substance P and prevents reaccumulation
Pharmacodynamics/Kinetics
Onset of action: 14-28 days
Peak effect: 4-6 weeks of continuous therapy
Duration: Several hours
Dosage
Children
2 years and Adults: Topical: Apply to affected area at least 3-4 times/day; application
frequency less than 3-4 times/day prevents the total depletion, inhibition of synthesis, and
transport of substance P resulting in decreased clinical efficacy and increased local discomfort
Administration
Wear gloves to apply; wash hands with soap and water after applying to avoid spreading to
eyes or other sensitive areas of the body.
Patient Education
For external use only; wear gloves to apply; wash hands immediately after application;
discontinue if severe burning or itching occurs; if symptoms persist longer than 14-28 days,
contact physician
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic
Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
None reported
Dosage Forms
Cream, topical: 0.025% (60 g); 0.075% (60 g)
ArthriCare® for Women Multi-Action: 0.025% (42 g) [contains menthol]
ArthriCare® for Women Silky Dry: 0.025% (42 g)
ArthriCare® for Women Ultra Strength: 0.075% (42 g) [contains benzalkonium chloride and
menthol]
Capzasin-P®: 0.025% (45 g)
Capzasin-HP®: 0.075% (45 g)
Zostrix®: 0.025% (60 g)
Zostrix®-HP: 0.075% (60 g)
Gel, topical (Capsagel®): 0.025% (60 g); 0.05% (60 g); 0.075% (30 g)
Lotion, topical (ArthriCare® for Women Extra Moisturizing): 0.025% (120 mL, 240 mL)
Patch, topical (TheraPatch® Warm): 0.09% (6s) [DSC]
Stick (Zostrix® HP): 0.075% (21 g) [DSC]
International Brand Names
Antiphogistine Rub A-535 Capsaicin (CA); Axsain® (GB, IE); Capsicin® (ES); Capsicum
Farmaya® (ES); Capsidol® (ES); Capsina® (SE); Casacine® (CO); Dolpyc® (BE, IT); Gelcen®
(ES); Katrum® (ES); Presyc® (CL); Zacin® (GB, IE); Zostrix® (AU, CA, IL); Zostrix® H.P.
(CA)