This was presented as a lecture at the ASA national meeting.
Neuropathic pain is one of the most complex and difficult management challenges physician anesthesiologists face. Hundreds of distinct neuropathic pain syndromes have been documented and many are refractory to multiple treatments.
“Neuropathic pain affects 18 percent of the general U.S. population,” said Jianguo Cheng, M.D., Ph.D., Professor and Director of the Pain Medicine Fellowship Program at the Cleveland Clinic in Cleveland. “It is a major part of our practice and very resource-intensive. Medical costs for neuropathic pain patients are threefold higher compared with matched control subjects.”
Neuropathic pain is caused by a lesion or insult in the peripheral or central nervous system. The resulting plasticity in the peripheral and central nervous system leads to sensitization and hyperexcitability of neurons in the dorsal root ganglion, the spinal cord and the brain. The result is hyperalgesia, allodynia and spontaneous pain.
Causes include post-surgical, post-traumatic or post-herpetic neuralgia, diabetic neuropathy, HIV neuropathy, hypothyroidism, toxic exposures, lesions of the central nervous system, complex regional pain syndromes and more.
“Treatment of neuropathic pain has two goals,” said Timothy Lubenow, M.D., Professor of Anesthesiology, Rush University Medical Center, Chicago. “We want to alleviate or eliminate the cause of the underlying disease and to relieve symptoms.”
Treating the underlying cause is vital to long-term control, he said. For example, it is virtually impossible to successfully treat diabetic neuropathy until the underlying diabetes is brought under control.
Step therapy is standard for treating neuropathic pain, Dr. Lubenow said. Most patients can be treated with drug therapy, typically combinations of agents with different mechanisms of action. Multiple medical societies have issued guidelines for neuropathic pain, most with somewhat different recommendations. There are a wealth of anecdotal reports and open-label studies, and a dearth of strong evidence.
“When the evidence is soft, it is more open to interpretation and opinion,” he said. “You want a drug or a combination of drugs that are useful in alleviating pain, but you also want to minimize side effects.”
Pregabalin, gabapentin and duloxetine appear as preferred agents in most guidelines, Dr. Lubenow said. Other agents frequently recommended include sodium valproate, oxycarbazepine, venlafaxine, amitriptyline, dextromethorphan tramadol, morphine, oxycodone and capsaicin.
For patients with recalcitrant pain, spinal cord stimulation and intravenous infusion may be viable alternatives.
There are data supporting the use of I.V. lidocaine, bisphosphonates, phentolamine and immunoglobulin, said Philip Peng, M.B.B.S., Professor of Anesthesiology and Pain Management at Toronto Western Hospital, University of Toronto. But the duration of analgesia tends to be short, and severe adverse events are common.
Ketamine is one of the most promising I.V. agents for neuropathic pain, he said. Most studies use 50 mg or less infused over 30 minutes to two hours and the analgesic effect lasts less than two days. Trials using larger doses over longer infusion periods show much greater effect.
A study using anesthetic doses infused over five days showed significant pain relief up to six months following treatment, but there were significant psychotropic effects, muscle weakness and infections. Later trials using lower doses showed less severe adverse events but also less analgesia.
Early data from a Toronto Western Hospital trial using six-hour outpatient infusions for five days showed slightly more non-responders than responders, Dr. Peng reported. But responders showed greater than 50 percent pain relief up to three months after treatment.
“Responders tend to have less pain by the end of the second day,” he said. “At this point, we have no good tool for predicting responders. We are hoping for more robust data as the protocol progresses.”