Discussions that mention ketamine

Pain Management board


Drugs that block NMDA receptors can also have important pain-relieving effects. In caring for patients who have illicitly used the potent NMDA receptor-blocker phencyclidine ("angel dust"), I have been repeatedly impressed by how many of them can tolerate the extreme pain of gunshot wounds or fractures. Unfortunately, phencyclidine's psychotomimetic effects make its use as a pain reliever impractical.

With careful use, other NMDA receptor-blockers such as ketamine can undo at least some of the damage done by chronic pain. It is interesting to note that, while nearly all of the powerful pain-relieving opioids are levorotatory, their dextrorotatory isomers are often noncompetitive NMDA receptor-bockers. One example is dextromethorphan, the D-isomer of levorphanol. Another is methadone, which is formulated as a racemic mixture that can both activate opioid receptors and block NMDA receptors. In patients who have become tolerant to opioids, these drugs can often restore sensitivity, even to small doses. Unfortunately, clinical use of these drugs, with the exception of methadone, is currently limited because they not only block NMDA receptors in the spinal cord but also in the brain, where they can reverse learned inhibitions and induce transient psychosis. Current research should soon yield ways of formulating and delivering NMDA receptor-blockers that will ease most chronic pain syndromes without causing such adverse effects.

The finding that enkephalins work by closing N-type calcium channels, which are found only in neural tissue, prompted a search for drugs that would block these channels specifically. One of the compounds isolated, ziconotide, derived from the venom of a fish-hunting sea snail, has shown promising results in clinical studies of patients with intractable opioid-resistant pain.

Gabapentin, an anticonvulsant widely used for treatment of neuropathic pain, also inhibits calcium flux through N-type channels. Despite its name, gabapentin does not appear to have any effect on GABA receptors. However, GABA-agonist medications such as baclofen are among the drugs being investigated for GABA-like pain-relieving effects.

As new findings about the various elements of the antinociceptive system have emerged, a number of other drugs are being reevaluated for analgesic potential. The observation that alpha2-adrenergic receptors are involved in inhibiting pain signals, led to reformulation of the oral hypertensive agent clonidine as a potent intrathecal pain reliever. The demonstration of clonidine's benefits in treating chronic pain syndromes has focused attention on other alpha-adrenergic drugs. Both tizanidine, an antispasmodic agent, and oxymetazoline, a nasal decongestant, are currently being assessed for their utility as pain relievers.


Clinical Lessons
In tracing the pathways of acute and chronic pain, we see that they are very different processes--so different that some investigators have proposed that they be referred to by separate names, eudynia and maledynia. Chronic pain (or maledynia), unlike normal everyday pain, is a destructive disease with physical, psychological, and behavioral consequences.

Unlike patients with acute pain, those with chronic pain often appear to be depressed, or even vegetative, and many show signs of psychomotor impairment. Another characteristic of these patients is that, in the course of giving their histories, they frequently refer to events and losses that appear to be only peripherally related to the focus of their evaluation. Although this is usually interpreted as evidence of a characterologic disorder or psychiatric illness, it could be a manifestation of the neurochemical link between pain and memory.

The failure to realize that behavioral and psychologic changes can reflect pathologic changes in the nervous system often prevents patients with chronic pain from getting the timely and aggressive care that they need. The clinical take-home lesson is that we can reverse the signs and symptoms of chronic pain with proper treatment. Part two of this article will make the case that opioid medications, although broadly feared and highly restricted, can be the mainstay of safe, effective treatment for chronic pain disease.


Take care, Dave