The Diagnosis and Treatment of Neuropathic Pain

Oct 06, 2020 at 10:23 am by admin

Julio Olaya, MD

Neuropathic pain is an important medical topic and the diagnosis of it should be understood by any medical provider regardless of their specialty. It is a condition that also presents in primary care but is often unrecognized.

When referring to neuropathic pain, it is important to understand the definitions that have been evolving through time. In 1994 it was defined as "Pain initiated or caused by a primary lesion or dysfunction in the nervous system." In 2008, the IASP (The International Association of Study of Pain) changed it to: "Pain arising as a direct consequence of a lesion or disease affecting the somatosensory system" giving it a broader connotation. The bottom-line is that neuropathic pain is a complex entity that involves a multidisciplinary approach to diagnose and treat.

Neuropathic pain, or nerve pain, is one of the most intense types of chronic pain, often described as sharp, stinging, or burning. The literature reports an overall prevalence of neuropathic pain in the population of up to 8 percent.

Neuropathic pain can be peripheral or central. The etiologies are many: trauma, ischemia, infection, inflammation, cancer therapy, compression, etc.

The following are some examples: Trauma: phantom limb pain and spinal cord injury, Ischemic: Post-stroke pain (central), diabetic neuropathy peripheral, Infection: Post-herpetic neuralgia (shingles) and HIV, Cancer drugs: Vinka alkaloids, monoclonal antibodies among others, Compression trigeminal neuralgia, and Multiple sclerosis without a clear cause but lately very well recognized as a real source of neuropathic pain.

The first step in the diagnostic work up is no different from other areas of medicine; a meticulous collection of the medical history, focusing on exploring the onset of pain and the possible association with current diseases, trauma, surgery, etc. All neuropathic pains are perceived within the innervation territory of the damaged nerve or pathway due to the somatotopic organization of the primary somatosensory cortex.

Symptoms of neuropathic pain include:

  • Severe pain, which may feel like shooting, throbbing, or burning
  • Electrical-like sensations
  • Numbness
  • A tingling sensation, or pins and needles
  • Reduced use of senses, such as difficulty sensing temperatures
  • Skin that appears mottled or red
  • Itchiness
  • Changes in pain associated with the weather.

Neuropathic pain can also cause patients to be overly sensitive to touch. For example, people may find that the slightest pressure or friction from clothing or a gentle touch can aggravate nerves and cause pain. (Allodynia).

Neuropathic pain can occur at all time or come in spurts. Likewise, neuropathic pain can range in intensity from being mild and nagging to severe and disabling.


Treatment of neuropathic pain first entails addressing the underlying cause. For example, if a patient has neuropathic pain from diabetes, optimizing blood sugar (glucose) control is the critical first step. Even though an effective glucose control will not reverse the neuropathy, it will prevent it from getting worse. As another example, if a medication is causing debilitating nerve pain, removal or decrease in the dose of the offending drug may be all that is needed.

First line medications:

Along with treating the underlying disease, medication is often needed to manage the neuropathic pain.

Antidepressant and antiseizure medications are used as the first line of treatment all come with a black-box warning about their ability to cause suicidal thoughts and behaviors.


Antidepressants have a well-established beneficial effect in various neuropathic pain states. These include: TCA's (e.g., amitriptyline and imipramine) and the SNRI's (duloxetine and venlafaxine), while the effect of the SSRI's is lower. When we decide to prescribe these medications, we need to take into consideration their potential undesirable side effects, and we will have to tailor the medical plan considering the different co-morbidities that our patient might have.

TCA's have several side effects; the most important ones are cardiac conduction disturbances, dry mouth, urine retention, sedation, dizziness, and orthostatic hypotension. An electrocardiogram is mandatory before onset of treatment.


Anticonvulsants drugs are primarily introduced for the treatment of epilepsy. They have several pharmacological actions that can interfere with processes involved in neuronal hyperexcitability, either by decreasing excitatory or increasing inhibitory transmission, thereby exerting a net neuronal depressant effect.

Gabapentin is a structural analog to gamma-aminobutyric acid (GABA) that has no effect at GABAergic receptors but binds to the alfa2delta subunit of voltage-dependent Ca++ channels therefore reducing the calcium influx into cells. Gabapentin has shown efficacy in painful diabetic neuropathy, postherpetic neuralgia, mixed neuropathic pain conditions, and phantom limb pain.

Pregabalin is a GABA analogue related to gabapentin that has also shown efficacy in neuropathic pain.

Gabapentin and pregabalin are generally well tolerated and have no drug interactions but should be administered in smaller doses in patients with renal failure. The adverse side effects include dizziness, sedation, and occasionally, peripheral edema.

Lamotrigine blocks voltage-dependent Na+ channels and inhibits Na+ influx-mediated release of excitatory amino acids from presynaptic neurons. In small trials, lamotrigine has shown efficacy in trigeminal neuralgia, HIV neuropathy, painful diabetic neuropathy, and central poststroke pain at doses of over 200 mg/day. Lamotrigine is usually well tolerated. Side effects include rash, dizziness, and somnolence. Because of the rash, which in severe cases may progress to Stevens Johnson syndrome, the lamotrigine must be titrated slowly.


There is a misconception that neuropathic pain responds well to opioids, there is nothing further from the truth... opioids are the last option when treating neuropathic pain.


Lidocaine blocks the voltage gated sodium channels, and topical application is thought to silence ectopic discharges on small afferent fibers. Lidocaine patches are used in the treatment of postherpetic neuralgia and in mixed peripheral focal neuropathy.

Topical capsaicin. Topical applied capsaicin has shown a significant effect in diabetic neuropathy and in postherpetic neuralgia. The use of capsaicin is very limited because of the inconvenience of applying the cream to the painful area four times a day.


Damage or injury to the nerves can cause neuropathic pain. Symptoms can range from mild to severe.

Neuropathic pain commonly presents in primary care and is underdiagnosed.

Diagnosis is based on characteristic symptoms, altered sensations, and clinical history that matches a neuroanatomical or dermatomal pattern.

Less than half of the patients achieve significant benefit with any single drug.

Management includes making pain tolerable and maintaining emotional and physical functioning.

Non-pharmacological approaches can be effective, but referral for specialist help is indicated if pain persists or remains uncontrolled.

Some types of neuropathic pain may ease or resolve over time, while other types will require long-term pain management.

Julio Olaya, MD is a board-certified anesthesiologist specializing in pain medicine at Arkansas Spine and Pain Center of Excellence.

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