Local anesthetics are effective for neuropathic pain

October 25, 2005

Lidocaine and similar local anesthetics are effective for treating pain that emanates from damaged nerves, according to a systematic review of current evidence.

Neuropathic pain, which can occur with chronic diseases or conditions, is frequently unresponsive to treatment and worsens over time.

"Intravenous lidocaine and oral derivatives relieve pain from damage to the nervous system," found authors Ivo W. Tremont-Lukats, M.D., of the M.D. Anderson Cancer Center in Houston, and colleagues. They add that the drugs, "were safe in controlled clinical trials for neuropathic pain, were better than placebo and were as effective as other analgesics." [Read more]

Effect of sodium channel blocker (mexiletine) on pathological ectopic firing pattern in a rat chronic constriction nerve injury model

June 04, 2005

J Orthop Sci. 2005;10(3):315-20.
We studied the efficacy of mexiletine as a sodium channel blocker for neuropathic pain by investigating the effect of mexiletine on the pathological ectopic firing pattern in a chronic constriction nerve injury (CCI) model. The experiment was conducted with 60 male Wistar rats. The CCI model was created by loosely ligating the sciatic nerve. After breeding 7 days, the frequency and pattern of ectopic firing antidromically recorded from the sural nerve and the amplitude of antidromic sensory nerve-evoked potential were analyzed. The CCI rats were given an intravenous injection of normal saline and mexiletine (5 or 15 mg/kg). Mexiletine significantly suppressed spontaneous firing frequency, an on-off firing pattern that consisted of cyclic bursting spikes and ectopic firing generation under the hypoxic condition. Mexiletine did not influence the amplitude of A-delta component in the antidromic sensory nerve-evoked potential. Mexiletine suppressed ectopic firing by blocking activity of the abnormal sodium channel at the nerve-injured site and dorsal root ganglion without blocking nerve conduction. This study suggests that mexiletine is useful for treating neuropathic pain in peripheral neuropathy.

Blocking Pain by Gene Transfer

June 02, 2005

From Bioscience Technology: Researchers say they have developed a way to block the signals responsible for neuropathic pain. The group used a disabled form of the herpes simplex virus (HSV) as a vector to deliver genes to the nucleus of neural cells in rats.

"We use the vector to provide targeted gene delivery to the nervous system," says David Fink, MD, professor of neurology, University of Michigan Medical School, Ann Arbor, and a neurologist at the VA Ann Arbor Healthcare System, who co-directed the research study. "In this case, we're not trying to correct a genetic defect. Our goal is simply to deliver a gene to sensory nerve cells, so its product can be used to block transmission of pain signals from damaged nerves to the brain."

Neuropathic pain is a common complication of many diseases and medical conditions, especially diabetes. Drugs have little effect on this type of constant pain in the hands and feet, which is caused by damage to sensory neurons that transmit pain, temperature, and touch signals to and from the brain.

In a recent study in the Annals of Neurology the researchers describe how laboratory rats with nerve damage receiving injections of the HSV-based vector, which contained a gene called GAD, or glutamic acid decarboxylase, showed reduced pain-related behavior. The treatment's pain-killing effect lasted up to six weeks, they said, and even longer in rats that received additional injections.

The vector delivered GAD to the nucleus of nerve cells in the dorsal root ganglion near the spine. In previous studies, the researchers confirmed that the vector remains in the dorsal root ganglion, but an enzyme expressed by the GAD gene moves to nerve terminals in the spinal cord where it triggers production of a powerful neurotransmitter called GABA.

"GABA is the main inhibitory neurotransmitter in the nervous system," Fink says. "It's like a hall monitor for the nervous system; it damps down neurotransmission between cells to keep things quiet. You can't have every neuron talking to every other neuron all the time or you'd have chaos."

Other scientists have shown that decreased GABA activity in the spinal cord contributes to the development of neuropathic pain, says Fink. Physicians have drugs that block neural transmission by mimicking the actions of inhibitory agents like GABA, but it's difficult to give these drugs in adequate doses, because the same drug that blocks pain also interferes with brain activity, leaving people drowsy and unable to think clearly.

They believe HSV has a natural ability to travel long distances along nerve fibers to reach the neural cell's nucleus, which makes it the perfect gene delivery vehicle for use in the nervous system.

"What we need is a way to release GABA in the spinal cord where it can selectively block incoming pain signals from peripheral nerves," says Fink. "If we can block transmission of the signal at the first neural synapse, it will never reach the brain and you won't feel pain. As long as the GAD gene remains active, GABA will continue to flood the spinal cord and block the transmission of pain signals to the brain."

The study, they say, is the first to demonstrate the successful use of gene transfer technology using a herpes viral vector to treat peripheral neuropathic pain in animals. The group hopes to conduct the first clinical study in human patients soon. They also plan to conduct the first phase I safety trial of a related HSV vector in patients with pain caused by terminal cancer that has spread to bone.

Treatment of painful polyneuropathies

June 01, 2005

From Current Pain and Headache Reports 2005, 9:178-183

The treatment of painful polpyneuropathies has begun to improve over the past several years. This is based on an evolving understanding of the pathogenesis related to the development of diabetic neuropathy and other diseases that may lead to peripheral nerve injury. Consensus on evaluation strategies for patients presenting with pain has furthered our ability to define neuropathic pain and accompanying signs and symptoms that may respond to particular therapeutic approaches. Recent therapeutic advances in medical management have demonstrated improved outcomes in pain relief. This, along with lower side effect-related issues, has led to improved compliance and patient satisfaction. The assessment and treatment of comorbid conditions, which include sleep, anxiety, and depression, have further advanced the management of painful polyneuropathies in patients. New antiepileptics, antidepressants, and topical therapies have contributed to improved patient outcomes.