Neuropathic Pain

(Date of publication 02 April 2004)

When we suffer burns, sprains, bruises or inflammation, nearby receptors transmit pain signals via the peripheral nerves and spinal cord to the brain. This gives rise to the nociceptive pain which everyone has experienced; typically it is localised, constant, often has an aching or throbbing quality and is time-limited, so that when the lesion heals the symptoms disappear. However, another type of pain, often long-lasting, originates in the nervous system itself - neuropathic pain. Burning, lancinating or ‘electric shock’ qualities may be present and patients may experience allodynia (pain resulting from a non-noxious stimulus such as touch) or hyperalgesia (increased sensitivity to painful stimuli), sometimes in a region of the body remote from the pain. Bizarrely, it may even appear to originate from outside the body...

Diagnosis of neuropathic pain is largely from the medical history, and common causes include diabetes, multiple sclerosis, shingles, trigeminal neuralgia and amputation. Two broad categories may be defined; deafferentation pain due to interruption of afferent neural activity, and sympathetically maintained pain which is dependent on efferent sympathetic activity. Accurate diagnosis is essential to determine the category of pain and thus determine treatment, and also to differentiate deafferentation pain due to peripheral nerve damage from that caused by a potentially treatable pathological process.

Whereas nociceptive pain generally responds to opioids and non-steroidal anti-inflammatory drugs (NSAIDS), neuropathic pain is more difficult to treat and responds only partially to opioid therapy. The complex peripheral and central mechanisms involved - such as long term potentiation (LTP), ephapses and CNS plasticity - are explained on the Spineuniverse site, but you will need a fairly comprehensive knowledge of pain theory to tackle it.

The symptoms experienced by the patient depend upon the specific cause. For example, diabetic neuropathies can damage nerves throughout the body, leading to numbness, pain and weakness in the limbs, as well as problems with the digestive tract, heart and sex organs. Almost 50% of diabetics have some sort of neuropathy, and these appear to be more common in those individuals who have difficulty controlling their blood glucose levels. Neuropathic pain, particularly that associated with focal neuropathy, in which a specific nerve or group of nerves is affected, can be sudden and severe. It may be treated with analgesics including aspirin, paracetamol, NSAIDs and codeine, but tricyclic antidepressants or anticonvulsants such as carbamazepine and gabapentin are effective in some patients.

These treatments are described more extensively on the Harvard diabetes site, which also advances a number of theories for the mechanism by which high blood glucose levels lead to nerve damage. One is that the excess sugar reacts with the enzyme aldose reductase in Schwann cells surrounding the nerves, causing them to swell and cause compression. Others are that certain intracellular metabolites become depleted and that the protein kinase C pathway is triggered, while decreased bloodflow to the nerves is also thought to be a contributory factor. For a brief diversion from pain symptoms, this photo essay illustrates the damage to the feet that may arise as a result of diabetic sensory and motor neuropathy, including erosions and ulcers.

People who develop shingles (see photograph) may suffer neuropathic pain (post-herpetic neuralgia or PHN) for months or even years afterwards. This condition is associated with scarring of the dorsal root ganglion and atrophy of the dorsal horn on the affected side, following the extensive inflammation caused by herpes zoster. The incidence and severity of PHN are directly proportional to the age of the patient. There may be two types of pain, a steady burning or aching and a paroxysmal lancinating pain; both can occur spontaneously and may be aggravated by even light contact with the skin of the involved area.

The use of anti-viral drugs to treat shingles has been shown to reduce the duration and prevalence of PHN by as much as 50%, although 20% of patients over the age of 50 continue to report pain six months after the onset of symptoms. Once neuralgia has become established, the gold standard for treatment is the tricyclic antidepressant amitriptyline, which produces good pain relief in more than 50% of patients treated. For a review of other pharmacological agents and treatment modalities which may be employed, click here.

Trigeminal neuralgia, or tic doloureux, is a disorder of the fifth cranial nerve that generates episodes of intense, stabbing pain in an area of the face supplied by one of its three divisions, which are shown in this illustration. This syndrome is uncommon, with a prevalence of 155 cases per million people, but is widely considered to be the most painful affliction known to medical practice. Often, physical contact with trigger points precipitates pain; light touch or vibration are the most provocative, so that shaving, face washing or chewing may bring on an attack. Carbamazepine is considered by many physicians to be the medication of choice and is sometimes combined with baclofen, because this regimen may demonstrate synergistic properties. Surgery may be carried out if medical treatment is ineffective; the procedures of microvascular decompression and glycerol rhizotomy are described, complete with intra-operative photographs, here.

Let us complete the tour with the phenomenon of phantom limb pain, when patients experience stabbing, shooting or burning pain from a part of the body that has been removed, generally a limb but sometimes breasts, testicles or even an internal organ. It is important to distinguish this neuropathic pain from phantom sensations and stump pain. The causative mechanism is not known but there are diverse theories involving the peripheral nerves, the spinal cord and the brain. To read about these click here.

Anticonvulsants and antidepressants may be prescribed; gabapentin currently appears to be the most effective with the lowest incidence of side effects. Non-pharmaceutical therapies that can prove useful include transcutaneous electrical nerve stimulation (TENS), biofeedback and acupuncture. However, one of the most intriguing treatments, though not for pain, is mirror box therapy. In patients where the digits of the amputated limb feel to be constantly held in a clawed position, the normal limb is exercised alongside a reverse mirror image of it. This deceives the brain into thinking the amputated limb is still there and its digits are being moved. It sounds crazy - but it often works!

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A Tour around Neuropathic Pain

A Tour around Neuropathic Pain