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- Main article: Nervous system disorders
The four major forms of nerve damage are polyneuropathy, autonomic neuropathy, mononeuropathy, and mononeuritis multiplex. The most common form is peripheral polyneuropathy, which mainly affects the feet and legs.
There are other less common forms of neuropathy, for example
- Anterior ischemic optic neuropathy
- Enteric Neuropathy
- Ischemic optic neuropathy
- Small fiber peripheral neuropathy
- Wartenbergs migratory sensory neuropathy
Aside from diabetes (see Diabetic neuropathy), the common causes of neuropathy are herpes zoster infection, HIV-AIDS, toxins, alcoholism, chronic trauma (such as repetitive motion disorders) or acute trauma (including surgery), various neurotoxins and autoimmune conditions such as celiac disease, which can account for approximately 16% of small fiber neuropathy cases. Neuropathic pain is common in cancer as a direct result of the cancer on peripheral nerves (e.g., compression by a tumor), as a side effect of many chemotherapy drugs, and as a result of electrical injury. In many cases the neuropathy is "idiopathic," meaning no cause is found. A form of spinal nerve entrapment called Posterior Rami Syndrome can lead to neuropathic pain.
Neuropathy often results in numbness, abnormal sensations called dysesthesias and allodynias that occur either spontaneously or in reaction to external stimuli, and a characteristic form of pain, called neuropathic pain or neuralgia, that is qualitatively different from the ordinary nociceptive pain one might experience from stubbing a toe or hitting a finger with a hammer.
Neuropathic pain is usually perceived as a steady burning and/or "pins and needles" and/or "electric shock" sensations and/or tickling. The difference is due to the fact that "ordinary" pain stimulates only pain nerves, while a neuropathy often results in the firing of both pain and non-pain (touch, warm, cool) sensory nerves in the same area, producing signals that the spinal cord and brain do not normally expect to receive.
Treatment of neuropathic pain
A systematic review of randomized controlled trials found that the best treatments are tricyclic antidepressants, older anticonvulsants, and capsaicin. Tricyclic antidepressants include amitriptyline (Elavil®). Older anticonvulsants, valproate or carbamazepine (Tegretol®), were more effective than the newer anticonvulsants pregabalin (Lyrica®) and gabapentin (Neurontin®). In general, the antidepressants seem to be most effective on continuous burning pain, while the anticonvulsants seem to work best on sudden, lancinating, "shock-like" pains that appear to involve large numbers of peripheral nerves improperly firing together.[How to reference and link to summary or text]
In animal models of neuropathic pain it has been found that compounds which only block serotonin reuptake do not improve neuropathic pain. Similarly, compounds that only block norepinephrine reuptake also do not improve neuropathic pain. Compounds such as duloxetine, venlafaxine, and milnacipran that block both serotonin reuptake and norepinephrine reuptake do improve neuropathic pain.
Many of the pharmacologic treatments for chronic neuropathic pain decrease the sensitivity of nociceptive receptors, or desensitize C fibers such that they transmit fewer signals. The newer anticonvulsants gabapentin and pregabalin appear to work by blocking calcium channels in damaged peripheral neurons. Tricyclic antidepressants may also work on sodium channels in peripheral nerves. The anticonvulsants carbamazepine (Tegretol®) and oxcarbazepine (Trileptal®), especially effective on trigeminal neuralgia, are thought to work principally on sodium channels.
In some forms of neuropathy, especially post-herpes neuralgia, the topical application of local anesthetics such as lidocaine can provide relief. A transdermal patch containing 5% lidocaine is available. Ketamine in a transdermal gel is also frequently effective when the neuropathy is localized. Neurontin 100mg/g PLO gel is also effective for treating peripheral neuropathy, including Carpal Tunnel Syndrome. Capsaicin cream can be beneficial in several neurogenic pain disorders, which causes release of the pain neurotransmitter Substance P, and eventually reduces the availability of Substance P.
- Main article: antidepressants
Antidepressants usually reduce neuropathic pain more quickly and with smaller doses than they relieve depression. Antidepressants therefore seem to work differently on neuropathic pain than on depression, perhaps by activating descending norepinephrinergic and serotonergic pathways in the spinal cord that block pain signals from ascending to the brain.
- Main article: anticonvulsants
Reducing the sympathetic nerve activity
In some neuropathic pain syndromes, "crosstalk" occurs between descending sympathetic nerves and ascending sensory nerves. Increases in sympathetic nervous system activity result in an increase of pain; this is known as sympathetically-mediated pain. Reducing the sympathetic nerve activity in the painful region with local nerve blocks or systemic medications such as the alpha-blocker clonidine may provide relief. Other drugs, known for their ability to desensitize cardiac tissue, include beta-blockers such as propanolol and calcium channel blockers such as verapamil.
The N-methyl-D-aspartate receptor (NMDA) seems to play a major role in neuropathic pain and in the development of opioid tolerance.
Several opioids, particularly ketobemidone and methadone have NMDA antagonist activity in addition to their μ-opioid agonist properties that seems to make them effective against neuropathic pain, although this is still the subject of intensive research and clinical study. Methadone has this property because it is a racemic mixture; one stereo-isomer is a μ-opioid agonist; the other is a NMDA antagonist. Dextromethorphan is also known to be an NMDA antagonist at high doses.
Experiments in both animals and humans have established that NMDA antagonists such as ketamine and dextromethorphan can alleviate neuropathic pain and reverse opioid tolerance. Unfortunately, only a few NMDA antagonists are clinically available and their use is usually associated with unacceptable side effects.
Transcutaneous electrical nerve stimulation
Transcutaneous electrical nerve stimulation (TENS) is worth a trial in chronic neurogenic pain. Some pain management specialists will try acupuncture, with variable results. TENS, with certain electrical waveforms, appears to have an acupuncture-like function.
In more recent years, infrared photo therapy has been used to treat neuropathic symptoms. Photo therapy devices emit near infrared light typically at a wavelength of 890nm. This wavelength is believed to stimulate the release of nitric oxide, an endothelium-derived relaxing factor into the bloodstream, thus vasodilating the capilaries and venuoles in the microcirculatory system. This increase in circulation has been shown effective in various clinical studies, to decrease pain and improve sensation in diabetic and non-diabetic patients. Note that the U.S. FDA has not approved any infrared photo therapy devices to treat neuropathy.
In addition to pharmacological treatment there are several other modalities that help some cases. While lacking double blind trials, these have shown to reduce pain and improve patient quality of life particularly for chronic neuropathic pain: Interferential Stimulation; Acupuncture; Meditation; Cognitive Therapy; and prescribed exercise.
Alternative medicine treatments
There are 2 dietary supplements that have clinical evidence showing them to be effective treatments of diabetic neuropathy; alpha lipoic acid and benfotiamine. In several studies using a variety of dosages and routes of administration, alpha lipoic acid was found to reduce the various symptoms of peripheral diabetic neuropathy. A recent review of the published data determined “ALA should be considered as a treatment option for patients with peripheral diabetic neuropathy.” Also a recent study using orally administered alpha lipoic acid found that 600 mg once a day caused a marked reduction in the symptoms of diabetic neuropathy including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Benfotiamine is a lipid soluble form of thiamine that has several placebo controlled double blind trials proving efficacy in treating neuropathy and various other diabetic comorbidities. 400 mg a day was the most commonly studied dose.
New machines are available now from Rebuilder Medical Technologies to treat neuropathy.
- Compensatory hyperhidrosis
- Peripheral nervous system
- Phantom limb
- Phantom pain
- Posterior Rami Syndrome
- ↑ Up to 16% of Patients with Small Fiber Neuropathy May Have Celiac Disease. Celiac.com. URL accessed on 2007-26-06.
- ↑ Wong MC, Chung JW, Wong TK (2007). Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ 335 (7610): 87.
- ↑ Bennett G, Xie Y (1988). A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33 (1): 87-107.
- ↑ Seltzer Z, Dubner R, Shir Y (1990). A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 43 (2): 205-18.
- ↑ Kim S, Chung J (1992). An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50 (3): 355-63.
- ↑ Malmberg A, Basbaum A (1998). Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates. Pain 76 (1-2): 215-22.
- ↑ Sung B, Na H, Kim Y, Yoon Y, Han H, Nahm S, Hong S (1998). Supraspinal involvement in the production of mechanical allodynia by spinal nerve injury in rats. Neurosci. Lett. 246 (2): 117-9.
- ↑ Lee B, Won R, Baik E, Lee S, Moon C (2000). An animal model of neuropathic pain employing injury to the sciatic nerve branches. Neuroreport 11 (4): 657-61.
- ↑ Decosterd I, Woolf C (2000). Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87 (2): 149-58.
- ↑ Vadakkan K, Jia Y, Zhuo M (2005). A behavioral model of neuropathic pain induced by ligation of the common peroneal nerve in mice. The journal of pain : official journal of the American Pain Society 6 (11): 747-56.
- ↑ w23 Nelson KA, Park KM, Robinovitz E, Tsigos C, Max MB. High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology 1997;48:1212-8. PMID 9153445
- ↑ Abrams D, Jay C, Shade S, Vizoso H, Reda H, Press S, Kelly M, Rowbotham M, Petersen K (2007). Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 68 (7): 515-21.
- ↑ http://www.diabetesincontrol.com/burkearchive/nitricoxide9.shtml
- Special Interest Group on Neuropathic Painof the International Association for the Study of Pain (IASP)
- The Neuropathy Association
- The goals of the Canadian Neuropathy Association is to provide education to neuropathy patients, their families and their Doctors; conduct research and share information obtained as a result of that research
- A neuropathic series of articles from a neurologist who researches neuropathic pain
- Up to 16% of Patients with Small Fiber Neuropathy May Have Celiac Disease
- National Diabetes Information Clearinghouse
- Information about Neurology Article on marijuana's effect on neuropathic pain
- Nitric Oxide and its Role in Diabetes, Wound Healing and Peripheral Neuropathy
Nervous system pathology, primarily PNS (G50-G99, 350-359)
|Nerve, nerve root|
and plexus disorders
cranial nerve: V (Trigeminal neuralgia) - VII (Facial nerve paralysis, Bell's palsy, Melkersson-Rosenthal syndrome, Central seven) - XI (Accessory nerve disorder)
and other disorders of the PNS
| Diseases of myoneural junction|
Myasthenia gravis - Primary disorders of muscles (Muscular dystrophy, Myotonic dystrophy, Myotonia congenita, Thomsen disease, Neuromyotonia, Paramyotonia congenita, Centronuclear myopathy, Nemaline myopathy, Mitochondrial myopathy) - Myopathy - Periodic paralysis (Hypokalemic, Hyperkalemic) - Lambert-Eaton myasthenic syndrome
Drugs used for the treatment of fibromyalgia and neuropathic pain
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