Gulf Coast Pain Management
PERIPHERAL NEUROPATHY
 

Spinal and Peripheral Nerve Pain
The peripheral nervous system is outside of the central nervous system. Pain may be produced by many different types of lesions of the peripheral nervous system. Peripheral nerve pain may occur because of reflex sympathetic dystrophy or causalgia, herpes zoster, polyneuropathy, radiculopathy, plexopathy, and multiple entrapment neuropathies.

Peripheral Neuropathy
Peripheral neuropathy, or polyneuropathy, is a common syndrome and cause of peripheral nerve pain. It results in a common presentation of sensory and motor abnormalities termed stocking-glove dysesthesia. It presents as an impairment of sensation in the hands and feet. Weakness and wasting of muscle bulk, termed atrophy, is also common in peripheral neuropathy. Loss of reflexes in the extremities may also be found.

Diagnosis
It is important to determine the tempo of the illness. Is the disorder rapidly progressive over days or weeks, or is it progressive over months to years? Family history, the presence of underlying systemic illnesses, deficiency states, toxin exposure, and drug use are also important.
A careful history and physical should be performed. On physical exam, peripheral neuropathy may become evident. Sensory deficits may be present in the hands and feet and other parts of the distal extremities. Loss of reflexes may also be present. There may be atrophy, or loss of muscle bulk in the extremities.
Electromyography (EMG) may also yield information and help categorize the neuropathy.
Lab studies may also help determine the cause of the neuropathy.

Differential Diagnosis

• The differential diagnosis of peripheral neuropathy  includes:

• diabetes mellitus

• chronic alcoholism

• nutritional deficiencies

• amyloidosis

• paraneoplastic  conditions

• uremiaarsenic ingestion

• peripheral vascular insufficiency

• 25% to 50%  the cause remains unknown

Treatment

Treatment of the underlying condition supersedes the treatment of the discomfort.  In those situations where the cause of the peripheral neuropathy cannot be determined, treatment of the painful site is primarily symptomatic.

Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy  can be quite disabling.  Adequate sugar control in patients with diabetes was found to delay onset and slow the progression of the peripheral neuropathy. The symptoms  are usually gradually progressive and may begin with mild numbness, tingling, or a burning sensation in the feet.  Pain may occur later in the course of the disease.  Patients may describe hypersensitivity to touch of the feet and the ankles. In other individuals, there may be a loss of sensation in the feet, for that reason, diabetic patients are prone to injury of their feet and development of poorly healing ulcers, without their knowledge.  It is very important for diabetic patients to  examine their feet on a daily basis and maintain excellent follow up regarding any injuries or wounds on their feet.

Other treatments include the use of antidepressants, specifically, the tricyclic antidepressants (TCA’s), such as amytriptiline. These relieve pain by altering levels of serotonin in the body.  The antineuralgic properties of TCA’s were shown to be independent from their antidepressant properties.  TCA’s are associated with a number of adverse side effects such as sedation, orthostatic hypotension, dry mouth, urinary retention, constipation, and weight gain.  These side effects are more pronounced in the elderly.  TCA’s shold be used with caution in the elderly, patients with heart disease, narrow angle glaucoma, and prostatism. Another class of antidepressants, the selective serotonin reuptake inhibitors (SSRI’s), may also be used .  In general, the SSRI’s have not been found to be as effective as the TCA’s for the treatment of neuroptahic pain, but are better tolerated. The side effects of the SSRI’s include sweating, stomach upset, somnolence, dizziness, decreased libido, and ejaculatory disturbances.

Anticonvulsants have been found to decrease the intensity of the burning and lancinating (lightening bolt)  sensations experienced with neuropathic pain.  The most widely used anticonvulsant used at this time is gabapentin. The mechanism of action responsible for the antineuralgic properties of gabapentin is unclear. Its effect is at least partially modulated through central mechanisms, most likely athe the level of the spinal cord.  The most common side effects of gabapentin are drowsiness, somnolence, and generalized fatigue.  These side effects are usually transient, lasting an average of 2-3 weeks. The median effective daily dose ranges between 900-1200mg, although some patients respond to daily doses as low as 100mg and others require 3600mg. This drug does not have a lot of drug-drug interactions, which could be an attractive property for patients of polytherapy.

There have been several reports of promising effects by mexilitene for the treatment of painful diabetic neuropathy. Patients treated with intravenous lidocaine may notice temporary pain relief of discomfort.  If those patients are placed on oral mexilitene, they may continue to have relief of discomfort.  Side effects of mexilitene appear to be  few.  Caution must be used in patients with intracardiac conduction disease and these patients should be monitored by follow up electrocardiograms. Because of equivocal efficacy and potential for side effects, this drug should be reserved for patients who fail first line treatments.

Tramadol (Ultram) is a centrally acting, non-narcotic pain reliever. Recent studies have shown that it may also be effective for treatment of painful peripheral neuropathy at doses of at least 200mg a day.  The most common  adverse side effects of tramadol are dizziness, vertigo, nausea, constipation, headache, and somnolence.

Topical ointments may also be helpful. An over the counter ointment, capsaicin cream, may produce pain relief of diabetic peripheral neuropathy. Capsaicin is a product extracted from hot chili peppers.  Its mechanism of action is depletion of substance P, which is a chemical modulator of pain. Caution must be exercised during its application, with care to avoid eye and mucous membrane contact.  Significant side effects include a burning sensation at the application site, particularly when a large amount of cream is applied. A thin film of cream is all that is necessary to provide pain relief and may decrease the risk of  side effects. This cream (0.25% to 0.75%) needs to be applied 3 to 5 times daily to the areas of affected by pain. Other prescription ointments are available that consist of a combination of many of these different medications.  They are well tolerated and are minimally absorbed by the blood, which decreases the risk of side effects.

Narcotics It is generally agreed that peripheral neuropathic pain is not responsive to narcotics.  This drug is rarely used for treatment of neuropathic pain and should be reserved for patients that have failed all other therapies. 

Alcoholic Neuropathy 

Alcoholic neuropathy is probably the second most common type of peripheral neuropathy. In mild cases there may be sensory symptoms only, with complaints of burning or painful feet or painful paresthesias (lightening bolt-type sensations).  With more advanced cases, motor weakness is present.  In this condition the legs are always more affected than the arms.  An unsteady gait, termed cerebellar ataxia, may result from cerebellar degeneration. The neuropathy develops slowly with continued alcohol abuse, and if abstinence is achieved, recovery is generally slow.

This disorder is thought to be due to a deficiency of thiamine and other  B  vitamins.  The deficiency state may be due to inadequate dietary intake and decreased absorption of vitamins, as well  as greater need for thiamine..  Treatment for these individuals is abstinence from alcohol and nutritional supplements containing thiamine and Vitamin B complex. 

Uremic Neuropathy

Uremic neuropathy is a complication of chronic renal failure that may be present in 20% to 50% of patients with uremia.  The disease may become less frequent because of more effective treatment of chronic renal failure, including chronic hemodialysis and renal transplantation.

It presents clinically with a slowly progressive, predominately sensory neuropathy.  Cramps and unpleasant dysesthesias and paresthesias often occur primarily at arrest: they appear to be relieved by moving around or walking.  Muscle weakness may also be present.

The neuropathy usually stabilizes or improves with dialysis.  After renal transplantation, a rapid initial improvement is often seen within  1 to 6 months. 

Conclusions

Based on published evidence, the TCA’s and gabapentin are first line therapy for the treatment of painful peripheral neuropathies. For most drugs, it is essential to start  at a low dose, and to gradually titrate to an effective dose.  Starting at too high a dose or titrating too quickly can lead to early discontinuation of the drug because of side effects. 
Apprehension by the patient will make it difficult to reintroduce the drug and a potentially useful treatment modality will be lost.  If a patient experiences partial pain relief with one drug, a combination of two or more different classes of drugs can yield better pain relief.  In general, when a patient remains pain free for 3 months  on a treatment regimen, consideration of a slow taper should be given.  In the event that pain recurs, the treatment should be reinstituted.

If drug therapy is not successful in adequately relieving pain, consideration should be given to implantable therapies such as the spinal cord stimulator or intrathecal pump. New medications are being developed to utilize in the implantable intrathecal pump, that have successfully relieved the pain of peripheral neuropathy.  A trial is performed to determine if a patient is a candidate for either of these therapies.  If the patient receives greater than 50% pain relief during the trial, permanent implantation is then considered.

As with all pain disorders, stress can aggravate and increase pain symptoms.  Therefore, stress management and behavioral  modification are very important to achieve successful and long-lasting pain relief.