Neuropathic pain (NP) is a chronic pain condition caused by damage, disease, or activity in the nerve fibers themselves that affects the somatosensory system of the body. Most neuropathies coexist with inflammatory, visceral and/or nociceptive pain (stimulation of free nerve endings by a chemical, thermal, or mechanical event). The somatosensory system transmits information from nerve receptors through the spinal cord and into the brain. When the nervous system gets injured, chemical signals are sent out from injured neurons, which activate neighboring glial cells. In response, these glial cells produce neuroprotective reactions, which include the rele­ase of neurotrophins and cytokines. At the same time, leukocytes are often attracted to the injury site. These are key cellular markers of the neuroinflammatory processes that is thought to be present in most types of neuropathic pain.

In addition, since these brain-body paths are not static, they can shift dramatically in response to disease, injury, or even chemical activity produced by the part of the brain that regulates rational cognitive functions such as mood, expectation, empathy, impulse control and emotion. This abnormal sensory processing is part of what makes neuropathic pain so difficult to treat and control. But it is also the key to understanding the pain produced by spontaneous and overactive neurotransmitters and their receptors (where there is pain with no actual sensory stimuli), as well as learning how to modulate, control and correct changes in these pain pathways.

It is estimated that up to 10% of the global population experiences neuropathic pain. In the U.S. over 30 percent of all neuropathy is a result of diabetes. In addition to pain, neuropathy can cause muscle weakness or paralysis, numbness and gastric dysfunction.


  • Pain and other sensations can be episodic, periodic or continuous. Neuropathic pain can range from annoying to excruciating and debilitating—more often the latter.
  • Burning pain is the most common symptom of nerve damage
  • Abnormal sensations
  • Pain produced by stimuli that would not normally produce pain, like a breeze or a light touch (allodynia)
  • Pain when there is no sensory stimulus (paraesthesia)
  • Electric shock sensation
  • Sensation of coldness
  • Tingling
  • Numbness
  • Itching
  • Swelling

Types/Causes of Neuropathic Pain

  • Toxic – Exposure to chemo-radiation in cancer treatment. Exposure to isoniazid, thallium, and chemicals like lead and arsenic can also cause nerve damage.
  • Metabolic – Diabetes (see Diabetic Neuropathy on this site), vitamin B1 deficiency, alcoholism.
  • Trauma – Phantom limb syndrome, residual limb pain after amputation, complex regional pain syndrome (CRPS), spinal cord injury, stroke, lower back dysfunction, surgery.
  • Compressive – Nerve entrapment, cancer, trigeminal neuralgia, excessive external pressure on nerves, carpal tunnel syndrome, radiculopathy (compressed nerves of the spine).
  • Autoimmune – Multiple sclerosis, chronic inflammatory demyelinating polyneuropathy (CIDP), vasculitic neuropathy.
  • Infectious – Post-herpetic neuralgia (continued pain after shingles), Lyme disease, diphtheria, Chagas’ Disease, leprosy, HIV, Guillain-Barré Syndrome.
  • Congenital/Hereditary – Fabry’s Disease, Charcot-Marie-Tooth Disease (burning pain in the extremities), amyloidosis.


People with neuropathic pain often present with both physical and psychological comorbidities. With complex medical histories and a multitude of possible underlying causes, people with NP can be difficult to diagnose. Scientists have come to view neuropathic pain as neuroinflammation: an inflammatory response that is an immune reaction to tissue damage or irregularity.

What’s New

New work by Mark Cooper, PhD, at the University of Washington in Seattle, investigates imaging methods used to diagnose neuroinflammation. Using magnetic resonance imaging (MRI), researchers can image leukocytes as they rush into an injured nerve or injured brain tissue. Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) can image activation of microglia ― the immune cells that reside in the nervous system – and be seen. According to Dr. Cooper, these are key cellular markers of neuroinflammatory processes.  Imaging sites of activated microglia and infiltrating leukocytes in the nervous system is a huge advance for pain medicine. The possibility of seeing this activity will not only give doctors a way to clearly diagnose neuroinflammation, but to make informed decisions about treatment. To be able to see activity in the inflamed human nervous system may lead to researchers to determine which molecules activate specific cellular behaviors, and then control them pharmacologically.

Treatment Options

Neuropathic pain is difficult to control. After addressing and treating underlying causes where possible, much of the care centers on adopting a healthy lifestyle and addressing pain. Maintain optimal weight, avoid toxins, follow a physician-supervised exercise program, and eat a healthy diet to improve general health and gastrointestinal symptoms, correct any vitamin deficiencies and avoid alcohol. Exercise to reduce cramps, improve muscle strength and prevent muscle wasting in paralyzed limbs. Treat injuries immediately to help prevent permanent damage. Since smoking constricts nutrient-supplying blood vessels, it can worsen neuropathic symptoms. Maintaining meticulous foot care and treating wounds carefully is particularly important in people with diabetes and others who have an impaired ability to feel. All of these lifestyle habits create conditions that encourage nerve regeneration.

Surgery can provide immediate relief for neuropathies caused by entrapment, such as carpal tunnel and damaged spinal disks. In severe cases of other neuropathies, such as trigeminal neuralgia, a surgeon can destroy nerves, but this is a last resort and can produce complications.


Secondary-amine tricyclic antidepressants (TCAs) such as amitriptyline, nortriptyline, and desipramine, and dual serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine, venlafaxine, and milnacipran improve neuropathic pain in some patients and are considered first-line medications for this condition. Bupropion has also been shown to improve neuropathic pain in some but is considered a third-line treatment.


Pregabalin (Lyrica) and gabapentin (Neurontin) work by blocking specific calcium channels on neurons and are preferred first-line medications for diabetic neuropathy. The anticonvulsants carbamazepine (Tegretol) and oxcarbazepine (Trileptal) are especially effective in trigeminal neuralgia.


Opioids are not considered first-line treatments for neuropathic pain, but they remain the most consistently effective. Morphine, oxycodone, methadone and levorphanol, as well as tramadole, are considered second-line treatments.

Topical agents

Local anesthetics such as lidocaine or anti-inflammatory agents such as gallium maltolate can provide relief. Lidocaine can also be injected locally or administered via patch. Qutenza (NeurogesX) is a high-concentration capsaicin patch that has proved effective with a single, 60-minute application.

Other and Alternative Treatments

Cannabinoids have been shown to relieve multiple sclerosis-associated NP. Botulin toxin type A (BTX-A) given intradermally has been shown to relieve pain, possibly by relieving neurogenic inflammation. Two dietary supplements have displayed clinical evidence of efficacy in treating diabetic neuropathy: alpha lipoid administered by injection, and benfotiamine taken orally. Neuromodulators, spinal cord stimulators and deep brain stimulation have show significant complication rates and low rates of pain relief.

Combined Therapies

In most NP patients only partial relief is found, and side effects prevent dose escalation. Many times a combination of medications is used, aimed at giving an additive effect or a reduction of side effects. Ultimately, an integrative approach with a combination of medications and therapies is necessary for most people with neuropathic pain. Find a physician who is patient and willing to try different combinations of medications with a managed strategy, while tracking your pain-reduction responses.

Resources and Support

The American Chronic Pain Association (ACPA)
The American Diabetes Association
The Amputee Coalition of America (ACA)
The National Institute of Neurological Disorders and Stroke (NINDS)
The National Multiple Sclerosis Society
The Parkinson’s Disease Foundation (PDF)
The Reflex Sympathetic Dystrophy Association (RSDSA)
The Neuropathy Association™
The Trigeminal Neuralgia Association
Daily Strength Support Groups