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New Developments In Treating Neuropathic Pain

Today's post from usc.edu (see link below) looks at the progress being made in identifying the causes and developing new treatments for neuropathy. There are signs to be optimistic about, especially in the area involving subduing cytokines, which are produced naturally by the immune system and help with the spread of misdirected pain signals. We're still a long way away from over the counter medication that really helps but knowing the research is being seriously done helps us to keep going until something effective is found. 

Painfully Clear
by Eva Emerson

Physicians and researchers have begun to identify the cause and develop treatments that may quench the agony of neuropathic pain.

To people living with neuropathic pain, a poorly understood form of chronic pain, a caress may feel like a burning jolt of electricity, a paper cut more like a deep, searing wound. Unlike the sharp "Ouch!" of a bug bite, the cause of neuropathic pain is usually invisible. And while the pain of a bug bite fades as the skin heals, neuropathic pain persists and sometimes intensifies-even after healing is complete. Hypersensitivity becomes the norm. Worse, traditional painkillers, from aspirin to heavy-hitting opiates like morphine, offer little relief to patients.

Neuropathic pain most commonly results from surgery, injuries and diseases such as cancer, diabetes, stroke, AIDS and shingles. For the millions of Americans who live with it, the pain can severely limit functioning. It leaves others confined in a cycle of pain and depression, doubting whether they will ever escape it.

Just talking about the scores of cases of intractable pain he has seen during his more than 30 year career makes Ronald Katz, M.D., cringe. After all this time, he still remains moved by the agony of patients with hard-to-treat cases of neuropathic pain. "It's a terrible disease," says Katz, professor and chair of the USC Department of Anesthesiology.

Physicians from all over the country routinely ask Katz and colleague Jack Berger, M.D., Ph.D., director of the USC Pain Management Clinic, to review the cases of patients with the most unrelenting symptoms.

"Because they are so hard to cure, patients with neuropathic pain syndromes represent a majority of our clinic practice," Berger says. By the time many arrive at USC, they will have seen multiple doctors, tried a slew of unsuccessful treatments and have spent years living in agony.

Until recently, the outlook for these patients has been bleak. Now, physicians have identified treatments that do work in some patients. Scientists are beginning to understand the causes of the syndrome, allowing them to develop new kinds of drugs to quench the pain.

Scientists consider pain a sense, like touch or sight. Scattered throughout the body are tiny nerve endings called nociceptors that serve as pain sensors. They respond only to strong, potentially harmful stimuli like a hard pinch or a burning match.

Most pain serves some kind of purpose, says Berger, who has worked for decades to help patients overcome pain and to educate physicians about its management. Pain alerts the brain to an injury so that you can protect yourself. Touch a hot stove and the pain generates a reflex that pulls your hand away before you suffer a serious burn.

Not obvious to scientists is what could be the purpose of chronic pain, and especially chronic neuropathic pain. They understand that it begins when disease or trauma damages a nerve. These injured nerves send a barrage of pain signals to the brain. The persistent signals cause other chemicals to be released that make receptors more sensitive. Somehow, the volley of signals also brings about physical changes in the organization of nerve networks. Even the way a message of "pain" is understood by the brain plays a role in worsening the sensation. In a sense, "the brain overreacts to the signals," Berger says. And because other activity in the nervous system can promote the pain, feeling excited or stressed might worsen symptoms.

For all the suffering endured by people with neuropathic pain, they are more likely to earn the label of hypochondriac than elicit any sympathy.

"Neuropathic pain is difficult for physicians to understand, and they often miss the diagnosis," says Berger. "When traditional pain medicines don't work, patients may be accused of being crazy."

Part of the problem is that there are few objective measures of pain. "An MRI doesn't show pain," Berger says. Physicians must rely on the patient's admittedly subjective descriptions of how they are feeling.

Confirming a diagnosis of neuropathic pain is difficult, too, because the underlying injuries are not detectable. Strokes commonly cause hidden nerve trauma, and yet a doctor will not be able to identify why the patient is in pain. In some cases, what seem like trivial injuries can cause lifelong damage. Katz recalls one patient who dropped a book on her foot and developed chronic neuropathic pain.

A simple diagnosis can help, as can stress reduction and relaxation techniques. Studies show that patients with a variety of pain conditions do more poorly (including a higher suicide rate) when doctors cannot identify a reason for the pain. Reassuring a patient that it is not "all in your head" is important. "From my experience, it's clear that simply hearing that the pain is real helps many people tolerate the pain better," Berger says.
At the USC Pain Management Clinic, physicians do succeed in helping some people live pain-free.

Among the most effective pain drugs are those used to treat epilepsy. Anti-convulsants like Tagretol and Neurontin help to quiet the abnormal firings of nerves in the brain and central nervous system. For other patients, drugs originally developed to treat depression, such as the tricyclic anti-depressants, offer relief. Apparently, the anti-depressants help patients tolerate pain better, perhaps by dampening pain signals. Berger reports great success treating diabetes-related pain of the hands and feet with local anesthetic. USC physicians have tried a variety of creams and concoctions-including one with hot chili peppers on the ingredient list-to halt the pain in some people with limb and other peripheral pain. The chemical that makes chili peppers taste hot also triggers nerve endings in the skin to fire, which can drown out the incessant pain signals from the area.

For those who do not respond to more traditional methods, clinic staff offers something called neuroaugmentation systems-a way of stimulating the nervous system to alter the pain signals reaching the brain. Doctors may implant a small electrical spinal cord stimulator or a pump containing pain medications that are infused directly into the spinal fluid. After a short trial period, those who respond well have a permanent implant put in. In about two-thirds of these patients, pain is reduced by at least 50 percent on a self-reported measure of pain. "In this disease, that's real success," Berger says.

Short-term relief offers the lucky few a chance to break out of the chronic pain cycle. Amazingly, "some neuropathies do heal. If you can control the pain for three to six months the nervous system may be able to repair itself," says Berger

The next generation of drugs for neuropathic pain is now being tested in the laboratory and in trials with patients. Scientists have found some evidence that chemicals made by the immune system, called cytokines, may help promote the misguided pain signals in the nervous system responsible for the pain, leading them to investigate drugs that subdue cytokine response. A venomous sea snail produces a chemical called ziconotide that has been hailed as another potential new treatment. The compound continues to be tested for efficacy in patients. So far, results look good-Neurex Corporation of Menlo Park, Calif., which makes the compound, says the drug reduced pain in about half of patients in the study.

"There's a great deal of research going on right now," says Berger. "Although we still don't have a magic bullet, we offer a steady supply of empathy and compassion for people suffering from neuropathic pain."

http://www.usc.edu/hsc/info/pr/hmm/98-99winter/pain.html

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