"We used to think that when you injured yourself there was a signal sent into the nervous system, and when the injury healed, the signal stopped," explains Dr. Richard Payne, chief of pain and palliative care at Sloan-Kettering. That, it turns out, isn't always true. "If the pain is allowed to go on, it's possible for the nervous system to remodel itself," Payne continues, "to have changed itself in such a way that there is going to be ongoing pain even if the injury has healed."

What's more, say pain scientists, we now know why morphine, the standard by which all other analgesics are measured, and which blocks pain by glomming on to one type of receptor, isn't the panacea we've thought. The nervous system probably uses hundreds of different chemical messengers (neurotransmitters) and receptors (the loading docks on the surface of neurons where these messengers' pain signals are received) to convey pain sensation. (You'll soon be hearing a lot about new drugs to block both a spinal-cord receptor called NMDA and a neurotransmitter called Substance P.)

On one hand, the new knowledge explains why pain, especially long-term chronic pain, is often so hard to treat. But researchers also now have a slew of new information to work with and targets at which to aim. In the meantime, the task at hand has been to learn how to work with existing pain-treatment tools to deliver the best pain care possible while developing new ones that fit better, conceptually, with the new discoveries.

One approach that continues to gather steam is to improve the means of delivering pain killers into the system. The first example of this was patient-controlled analgesia (PCA), the now ubiquitous system that first emerged in the mid-eighties, which allows a post-op patient to manage pain relief by pushing a button that triggers the release of a bolus of morphine through his or her IV bag. PCA soon spawned other novel drug-delivery tools, including transdermal patches (some of which may soon be enhanced with electrical current, the better to drive drugs into the system more thoroughly). There are also new time-release versions of a wide range of narcotics in varying doses; tiny high-tech pumps that, when implanted under the skin, can be programmed to trickle a set dose of pain medication into the spine; a narcotic-infused lollipop (the mucosal surface lining the inside of the cheeks expresses drugs directly into the bloodstream); and the pièce de résistance, a morphine inhaler that's currently near FDA approval. The lollipop works nearly as fast as IV morphine, the inhaler faster, according to Fishman.

Another avenue for researchers is exploring new uses for existing drugs. Doctors like this approach because it gives them immediate tools -- drugs don't have to be reapproved by the FDA for such "off-label" use. The payoff thus far:

* Epilepsy drugs like gabapentin, topiramate, and carbamazepine, known to stop seizures, seem to have a similar effect on chronic pain such as that associated with diabetes and shingles.

* Clonidine, an alpha-2 agonist used to treat hypertension, binds to alpha-2 receptors and has also been useful in treating chronic pain.

* Dextromethorphan, the key ingredient in over-the-counter cough syrup, also helps block one type of receptor that seems to be associated with chronic nerve pain. It's being tested for use in a solution with morphine.

* Botulinum toxin, a diluted version of the toxin that causes botulism, has approval for treatment of dystonia, a cluster of disorders characterized by painful muscle spasms often associated with chronic pain, when it is administered by injection.

And then there are the new drugs -- those that have arrived, and those still in the pipeline. Celebrex and Vioxx, for example, which work like aspirin but without as many gastrointestinal side effects, have been a major breakthrough -- particularly for arthritis sufferers, a large component of the chronic-pain population.

A wide net also has been cast for drugs found specifically to block receptors like NMDA and neurotransmitters like Substance P. A number of prospects are either being culled from nature -- the skin of an Ecuadoran frog, for example -- or being built, molecule by molecule, in labs and are currently being tested in animals and humans. The most anticipated arrival is a new calcium-channel blocker; the as-yet-unnamed drug (code-named SNX-111), derived from a poisonous sea snail native to the Philippines, is in the last phase of clinical trials before submission for FDA approval.

There are also procedures designed for those who can't get relief by any other means. One involves giving injections that will either disable or kill problematic nerves. (Among the more popular new agents being tested is capsaicin, derived from hot chili peppers.) Other prospects use the relatively gentle electricity of radio-frequency waves. In one increasingly popular procedure, a fine wire filament is surgically inserted into the spine and connected to a pacemaker-like device implanted under the skin, then programmed to periodically buzz the wire with radio waves. "It jams the pain signals," says Fishman. "It's like what they do in wartime to the enemy's radio transmissions."