MAKE IT STOP
Imagine a life without pain. No pounding headache after a hellish day at the office. No cricked back after that awful night on Aunt Millie’s lumpy sofa bed. No pangs from injuries, childbirth or food poisoning--no pangs, either, to impel us to yank a finger from a flame, rest a broken leg or refrain from romping through poison oak.
Put that way, life without pain would be bad. And short. Once in a blue moon, a child is born without pain-sensing nerves and sets about exploring the world without the cautionary lesson of pain. As the years go by, the injuries pile up--from self-mutilation, damaged joints, infected wounds--until one of them finally proves fatal.
Pain, in other words, is incredibly useful from a survival point of view--a fact that is of no comfort whatsoever to anyone suffering from pain that just keeps coming and coming, for months, years, even decades.
Chronic pain--from arthritis, from cancers invading the body, from damaged nerves and tissues, or mysterious causes that doctors don’t understand--creates untold misery in the world, as well as untold hours lost from work. Headaches. Back pain. Facial pain. Intractable pain, sometimes, responding poorly to today’s drugs, leaving many sufferers demoralized and despairing.
“When a pain’s of short duration, you can cope with it,” says Dennis Turk, professor of anesthesiology at the University of Washington, Seattle. “But what do you do when there’s no end--when it’s 365 days a year, 24 hours a day? It’s no surprise that these people get depressed.”
What has been a surprise, though, are recent discoveries that could change the way scientists and doctors view pain.
“Pain is not just a symptom of an injury,” says Allan Basbaum, chairman of the department of anatomy at UC San Francisco. “Under some conditions, it’s really a disease of the nervous system.”
What Basbaum is saying is that pain nerves, when we’re injured, seem to subtly change--and those changes, if they stick around, can set people up for longer-term misery. Misery that might be avoided if the initial pain were nipped in the bud.
Such nipping should be easier in the future. For years, pain management has relied largely on two groups of drugs: opioids, derived from morphine; and nonsteroidal anti-inflammatory drugs (NSAIDs), a class of painkillers that includes aspirin and ibuprofen. Both groups, while immensely useful, have side effects, such as addictive potential and constipation for opioids, and stomach irritation for the NSAIDs. And they don’t work for all types of pain.
Today, though, scientists have homed in on a dizzying array of molecules our bodies use in the pain response. Many of them--including glutamate, substance P and the painful-even-to-pronounce tetrodotoxin-resistant sodium channel--offer different ways to interfere with the pain pathway.
Pain and Our Ability to Fight It
What is pain, anyway? This seems like a really stupid question. (Jab a pin in yourself, it hurts and you go, “yow!” right?) Yet a band of pain scientists didn’t think so back in the ‘70s, when they went into seclusion to properly define the term.
Pain, they agreed, is more than just the relay of a “something bad is happening” message from some part of our body.
Those messages are a huge part of pain, of course. Damaged tissue--from a cut or a scrape, or arthritis--dumps a slew of chemicals onto the special, pain-sensing nerves that run through our bodies. Many of those chemicals can activate the nerves--as can a rude slap or a hand on a hot stove. The nerves then zap electrical messages to the spinal cord and thence to the brain, where the message gets interpreted. What kind of pain? How much? And where in the body did it come from?
But sensing the pain is not the same as getting upset by it. In an operation that’s rarely performed nowadays--a cingulumotomy--nerves are cut in a region of the brain involved in the pain response. The result? A chronic pain patient who will now smile at you, and tell you, “I feel the pain. It just doesn’t hurt anymore.”
And even people who don’t opt for this procedure will vary greatly in how much they feel an incoming pain sensation. Certain cultures accept pain more readily. Certain people just don’t let pain get to them as easily. Plus, if people are focused on some tricky task, or if they’re excited, they’ll feel pain less.
“It’s the parable of the soldier who looks down after the fighting has stopped, sees blood on his boots and yells for the medic,” says Dr. John Loeser, professor of neurological surgery and anesthesiology at the University of Washington. “Or the athlete that fractured a bone but felt no pain.”
Our body’s pain-fighting system is responsible. Sometimes, when the brain’s got other pressing things to think about (like running away from a man-eating tiger or solving a differential equation), it shushes the pain signals, using several chemicals (including our body’s natural painkillers, the endorphins) to relay its “Be quiet!” message back down the spinal cord.
Why Does the Hurt Persist?
But in any case, pain at the time of an injury is one thing. What makes pain persist for years? With a condition like arthritis, the answer’s pretty simple: The injury doesn’t leave, so the pain doesn’t leave. Sometimes, though, pain remains even after an injury has healed. And in those cases, pangs are often due to changes wrought on the nervous system.
Some of those changes made perfectly rational sense when the tissue damage was there. For instance, pain sensitivity goes way up at the site of an injury--and that’s useful. If things that didn’t hurt before--such as simply walking--now become torture, you’re sure to keep weight off that sprain and let it heal.
But sometimes, nerves remain changed long after visible signs of healing. And there you are, still super-sensitive to stuff you once wouldn’t have cared about. Great.
What this means, say pain scientists, is that treating pain promptly could ward off trouble down the road.
“I believe there’s no reason to be stoic,” Basbaum says. “All the data--ours and others’--says that the persistence of pain is bad.”
Our nervous system can do other crazy things as well. Say you damaged some nerves in your original injury--and lots of chronic pains, such as pain in diabetes and many lower back pains, involve nerve damage. Now that the spinal cord doesn’t have those pain nerves coming in, it sometimes gets uppity and sends its own “I don’t care! I hurt anyway!” message to the brain.
Or sometimes, when tissues are damaged, other, non-pain nerves--like a regular old touch nerve, or a nerve that makes your blood vessels dilate when you’re excited--start growing where they shouldn’t. The result? Now your nervous system sends scrambled messages to the brain. Every time you’re touched at a particular place, or you get excited by something, you feel pain.
The list of ways the body can turn rogue and make you hurt goes on and on. Sometimes, damage from a stroke can make the brain think the body is hurting somewhere when it’s not. Sometimes, we can end up feeling pain at a different site from the actual source of a pain.
But luckily, the list of new drugs being explored is getting longer as well, though the ones found to work may take years to come to market. These drugs are getting more and more sophisticated, says Dr. Jack Berger, assistant professor of anesthesia at USC.
“As we learn more about the biology of pain, our drugs become more specific, and hopefully they’ll do just the good things, and not the bad things that the old drugs did,” he says.
Aspirin and the other NSAIDs, for instance, cut off pain by preventing the production of a key pain chemical, prostaglandin. But prostaglandins in other parts of the body, such as the gut, are beneficial. Thus taking NSAIDs does more than dull the pain; it can also cause stomach irritation, even ulcers. A new class of drugs--called COX-2 inhibitors--stomps just on the pain prostaglandins, so it doesn’t have that drawback. (COX stands for cyclooxygenase.)
Other drug development is aimed at helping the brain do its pain-damping job more efficiently, or stomping the pain signal from the get go, in a variety of ways. And there’s more and more interest in figuring out ways to stop those touch nerves and “excitement” nerves from growing where they shouldn’t. There’s increasing evidence, too, that women and men respond differently to the same medications.
What will all this knowledge and drug designing give us? A world not without pain, but at least without the long-term chronic pain that messes up far too many peoples’ lives?
The drugs will surely help, reckons Turk. But they won’t repair all the havoc that long-term pain can wreak.
“By the time the average patient comes to a pain specialist, they’ve had a seven-year history of pain, during which time they’ve had major changes in their lives,” he says. “It’s not only affected them physically. It’s affected them socially. Recreationally. Maritally. Emotionally. I doubt if there’s going to be any new magic pill that will take care of all those problems.”
