Neuropathic Pain – Causes, Complications, and Prevention.

Definition             

Neuropathic pain is defined as pain caused by a lesion or dysfunction in the nervous system. There is no noxious (pain causing) stimulus that is causing the pain. Rather, the pain results from inappropriate signals in the nervous system. Unlike physiologic pain, which serves to warn and protect individuals from possible or actual injury, neuropathic pain serves no useful purpose.

Some examples of peripheral neuropathic pain include:

• Postherpetic neuralgia (pain occurring after shingles);
• Diabetic neuropathy;
• Pain following limb amputation.

Types of Neuropathic Pain

Painful diabetic neuropathy

Having diabetes and high blood sugar levels can damage your nerves, especially those in the legs and feet. This condition – diabetic neuropathy – can cause pain as well as numbness and tingling.

Trigeminal neuralgia

Trigeminal neuralgia is a disorder of the trigeminal nerve – the nerve that supplies sensation to the face and controls some of the muscles involved in chewing. People with trigeminal neuralgia have episodes of severe facial pain that last from a couple of seconds to several minutes.

Post-herpetic neuralgia

About one in every 5 people with shingles (a painful rash is also known as herpes zoster) develops post-herpetic neuralgia – ongoing pain in the area that was affected by the rash. It occurs when the shingles virus damages the underlying nerves, and the resulting pain can last for months or years.

Phantom limb pain

This condition affects people who have had an arm or leg amputated, causing pain or discomfort in the area of the now-missing limb. The exact cause of phantom limb pain is not known, but it is thought to be due to changes in both the nerves of the affected limb and the central nervous system (brain and spinal cord) following amputation.

Mechanisms/pathophysiology

Neuropathic pain results from damage to an afferent pathway that can be the result of a disease, trauma, or dysfunction.

Ectopic nerve activity/Peripheral Sensitization This mechanism is responsible for pain sensed in the absence of external stimuli. Spontaneous nerve activity has been shown in both the injured nerve as well as uninjured neighboring nerves. This spontaneous activity is thought to be related to an increase in voltage-gated sodium channel expression. This increased expression allows for decreased activation thresholds and increased membrane excitability. Additional expressional changes of other channels (i.e. K⁺) are also likely to occur but are less studied at this point.

Protein regulation is also altered with nerve damage. For example, a protein TRPV1 (transient receptor protein V1) that is activated at noxious stimuli around 40 Celsius is downregulated at injured fibers but upregulated at nearby uninjured fibers. This may decrease the activation temperature (i.e. to 38 Celsius, near body temperature) and result in the sensation of noxious heat/burning stimuli near the site.

Central Sensitization Regular discharge from peripheral nerves causes a release of excitatory neuropeptides and amino acids in the dorsal horn. This leads to phosphorylation of NMDA and AMPA receptors and expression of voltage-gated sodium channels (similar to ectopic nerve activity). This results in neuronal hyperexcitability that can lead to allodynia and hyperalgesia via activation of mechanosensitive A-beta and A-delta afferent fibers connecting with second-order nociceptive neurons.

Inflammatory reaction Inflammation results in activation of microglia in the nerve as well as the dorsal root ganglion. A proinflammatory milieu is created including cytokines, chemokines, substance P, TNF alpha, etc. These factors facilitate neuropathic pain by further enhancing neuron excitability.

What causes neuropathic pain?

Neuropathic pain often seems to have no obvious cause. But some common causes of neuropathic pain include:

• Alcoholism
• Amputation
• Chemotherapy
• Diabetes
• Facial nerve problems
• HIV infection or AIDS
• Multiple myelomas
• Multiple sclerosis
• Nerve or spinal cord compression from herniated discs or from arthritis in the spine
• Shingles
• Spine surgery
• Syphilis
• Thyroid problems

What are the risk factors for Neuropathic Pain?

Anything that leads to loss of function within the sensory nervous system can cause neuropathic pain.

• As such, nerve problems from carpal tunnel syndrome or similar conditions can trigger neuropathic pain.
• Trauma, causing nerve injury, can lead to neuropathic pain.
• Other conditions which can predispose patients to develop neuropathic pain include diabetes, vitamin deficiencies, cancer, HIV, stroke, multiple sclerosis, shingles, and cancer treatments.

What are the Symptoms of Neuropathic Pain Exactly?

Each person’s symptoms of neuropathic pain may be different, but these symptoms are common:

• Shooting, burning or stabbing pain
• Tingling and numbness, or a “pins and needles” feeling
• Spontaneous pain, or pain that occurs without a trigger
• Evoked pain, or pain that’s caused by events that are typically not painful, such as rubbing against something, being in cold temperatures, or brushing your hair
• A chronic sensation of feeling unpleasant or abnormal
• Difficulty sleeping or resting
• Emotional problems as a result of chronic pain, loss of sleep, and difficulty expressing how you’re feeling

Complications of Neuropathic Pain

• Patients with chronic nerve pain may suffer from sleep deprivation or mood disorders, including depression and anxiety.
• Because of the underlying neuropathy and lack of sensory feedback, patients are at risk of developing injury or infection or unknowingly causing an escalation of an existing injury.

Diagnosis and Screening

If your doctor suspects you may have neuropathic pain, he or she will ask about your pain and any other sensations you experience, such as pins and needles or numbness. Your doctor will also want to know about any events or illnesses that may have caused it.

Your doctor will perform a physical examination, testing the nerves in the affected area. They may touch the skin in the affected area with cotton wool, toothpicks or warm or cool objects as part of the examination.

If your symptoms and physical examination suggest you have neuropathic pain your doctor can prescribe specific treatment for this type of pain.

To make a definite diagnosis of neuropathic pain, the underlying cause of the pain needs to be found. Your doctor may recommend tests including:

• Blood tests
• Nerve conduction studies (to measure how quickly your nerves can carry electrical signals)
• An MRI scan

Biopsy

Sometimes a biopsy (tissue sample) can help with diagnosis. A skin biopsy (looking for a reduced density of nerve fibres in the skin) or a nerve biopsy (looking for abnormalities in the nerve fibres) may be recommended.

Treatment and medications that cure Neuropathic Pain

Treatment of neuropathic pain first entails addressing the underlying problem. For example, if a person has neuropathic pain from diabetes, optimizing blood sugar (glucose) control is an essential next step. Bear in mind, though, enhanced glucose control cannot generally reverse the neuropathy, although it can prevent it from getting worse and ease current symptoms.

As another example, if a medication is causing debilitating nerve pain, removal or a decrease in the dose of the offending drug may be all that is needed.

First-Line Medications

Besides treating the underlying problem, medication is often needed to manage neuropathic pain.

For the vast majority of patients, treatment of neuropathic pain involves taking one of the following:

• An antidepressant like Cymbalta (duloxetine) or Elavil (amitriptyline)
• An anti-seizure medication like Neurontin (gabapentin) or Lyrica (pregabalin)

In terms of side effects, nausea is the most common side effect of Cymbalta. Elavil generally poses more of a problem, mostly because of its risk for heart toxicity, as well as other bothersome side effects, including:

• Dry mouth
• Constipation
• Urinary retention
• Lightheadedness or dizziness when standing up

Neurontin may cause dizziness, tiredness, confusion, and swelling in the lower legs. Lyrica may cause dizziness, tiredness, dry mouth, swelling, and blurry vision.

Second-Line Medications

Opioids like Vicodin (hydrocodone/paracetamol) and Percocet (oxycodone/acetaminophen) are not as effective for treating neuropathic pain and, thus, are considered second-line treatments. In addition to their questionable benefit, opioids are associated with several side effects.

The potential side effects of opioids may severely affect a person’s quality of life and include:

• Nausea and vomiting
• Constipation
• Itching
• Dry mouth
• Urinary retention
• Drowsiness
• Memory and thinking problems
• Slowed breathing

In addition to these side effects, there is a nationwide concern for opioid addiction and abuse, which must be considered.

Unique Therapies

There are some types of neuropathic pain that may require a unique treatment plan.

• For instance, if a person’s neuropathic pain is localized, as is often the case in postherpetic neuralgia, a topical (on the skin) therapy, like a lidocaine patch may be used.
• In other instances, surgery may be necessary—for example, to release a compressed nerve, as in carpal tunnel syndrome. In the case of a herniated disc, in which an inflamed spinal nerve is a culprit behind the pain, an epidural steroid injection into the spine is sometimes performed.
• Lastly, sometimes certain medications are used to treat specific neuropathic pain conditions. A classic example is a trigeminal neuralgia, which is characterized by severe, stabbing neck and facial pain. This disorder is treated with the anti-seizure medication, Tegretol (carbamazepine) or Trileptal (oxcarbazepine).

Complementary Therapies

There are a variety of complementary therapies that can help relieve neuropathic pain. These therapies are commonly used in combination with medications and include:

• Physical or occupational therapy
• Relaxation therapy
• Massage therapy
• Acupuncture

How to prevent Neuropathic Pain?

The best way to prevent neuropathic pain is to avoid the development of neuropathy.

• Monitoring and modifying lifestyle choices, including limiting the use of tobacco and alcohol
• Maintaining a healthy weight to decrease the risk of diabetes, degenerative joint disease, or stroke
• Using the good ergonomic form at work or when practicing hobbies to decrease the risk of repetitive stress injury are ways to decrease the risk of developing neuropathy and possible neuropathic pain.