Chronic pain is both one of the world’s most costly medical
problems, affecting 1 in every 5 people, and one of the most mysterious. In the
past two decades, however, discoveries about the crucial role played by glia —
a set of nervous system cells once thought to be mere supports for neurons —
have rewritten chronic pain science.
اضافة اعلان
These findings have given patients and doctors a hard-science
explanation that chronic pain previously lacked. By doing so, this emerging
science of chronic pain is beginning to influence care — not by creating new
treatments, but by legitimizing chronic pain so that doctors take it more
seriously.
Although glia are scattered throughout the nervous system and
take up almost half its space, they long received far less scientific attention
than neurons, which do the majority of signaling in the brain and body. Some
types of glia resemble neurons, with roughly starfish-like bodies, while others
look like structures built with Erector sets, their long, straight structural
parts joined at nodes.
When first discovered in the mid-1800s, glia — from the Greek
word for glue — were thought to be just connective tissue holding neurons
together. Later
they were rebranded as the nervous system’s janitorial staff, as they were
found to feed neurons, clean up their waste and take out their dead. In the
1990s they were likened to secretarial staff when it was discovered they also
help neurons communicate. Research over the past 20 years, however, has shown
that glia don’t just support and respond to neuronal activity like pain signals
— they often direct it, with enormous consequences for chronic pain.
If you’re hearing this for the first time and you’re one of the
billion-plus people on Earth who suffer from chronic pain (meaning pain lasting
beyond three to six months that has no apparent cause or has become independent
of the injury or illness that caused it), you might be tempted to say that your
glia are botching their pain-management job.
And you’d be right. For in chronic pain, researchers now
believe, glia drive a healthy pain network into a dysregulated state, sending
false and destructive pain signals that never end. Pain then becomes not a
warning of harm, but a source of it; not a symptom, but, as Stanford pain
researcher Elliot Krane puts it, “its own disease.”
How the pain system works — and goes awry.
The pain system generally works in three distinct stages.
First, when an injury or ailment causes damage — let’s say you
just touched a hot pan — long nerve fibers in your finger sense the damage and
shoot a pain message toward your brain. In the second stage, those signals
enter your spinal column and, in a handoff monitored and sometimes tweaked by
nearby glia, jump to other neurons within the spinal cord. Finally, in this
alarm system’s third stage, those spinal cord neurons carry the signals to a
spot in your cerebral cortex related to your fingertip and create the sensation
of burning pain. You curse.
The first part of this alarm system — carrying the pain signal
toward the central nervous system — runs largely on a highly efficient
autopilot. Its main players are the long pain-sensitive neurons that run from finger
to spinal cord and quickly trigger a reflex that makes you jerk back your hand.
In stage two, when these signals approach the brain and spinal
cord, however, things get tangly. It is here, at the handoff from peripheral to
central nervous system, that a profusion of glia heavily regulate pain signals
by, say, amplifying or decreasing their intensity or duration. And it’s here
that things can go amiss and trigger chronic pain. As a flood of recent
research has shown, chronic pain develops because the glia accelerate the pain
system into an endless inflammatory loop that provokes the nerves into
generating a perpetual pain alarm.
It’s still not clear exactly how or why this glial mismanagement
develops. It can emerge either after an injury or seemingly out of nowhere.
Pain from one or even multiple injuries, as in a car wreck, ordinarily lasts
days or weeks and then tapers off to nothing. But sometimes the glia’s
regulatory system continues the pain signals after the tissue heals. These may
even spread to other areas, causing yet more pain.
Glia can create a tough mess to untangle.
In theory, identifying glia as chronic pain’s culprits should
make it easier to find a solution. Unfortunately it hasn’t, at least not yet.
You can’t just knock glia out — they’re too important — and current painkillers
don’t help because they target neurons, not glia.
And glia are ludicrously versatile. They transmit information
through dozens of communication pathways. “Pretty much every way that neurons
communicate,” said Doug Fields, a glia researcher with the National Institutes
of Health, “glia also use.” In a kinder world, these pathways would offer
targets for drugs or other treatments. But in the dauntingly complex systems in
which glia operate, those targets have so far proved fruitless. No treatment
has yet made it from bench to bedside.
This shouldn’t surprise us, said Fields: “Neuroscientists have
studied neurons for over a century, but they are playing catch-up with glia.”
David Clark, a Stanford pain researcher and clinician at the
Palo Alto Veteran’s Affairs hospital, suspected that part of the problem lies
in the pain system’s built-in redundancy. Glia seem to have so many ways to
transmit pain signals that even if a treatment blocks one, they promptly find
another. Clark believes that outwitting this vast system of glial regulation
may require novel strategies.
“This is not going to offer up a target you can just hit with a
drug or a genetic switch. It may require something wholly new, like figuring
out how to turn off an entire family of genes
at some crucial spot,” Clark said.
Your pain has a source.
The realization over the past 20 years that glia underlie
chronic pain does offer two substantial sources of comfort.
For one, scientists now at least have some idea where to seek a
solution — the glia. They haven’t yet found easily detectable biomarkers that
could demonstrate in a live person that glia (or other elements) are causing
chronic pain. But the underlying science is robust and steadily growing more
so.
For pain sufferers, this is a welcome validation of their
reality. “Learning this,” said Cindy Steinberg, the national director of policy
and advocacy at the
U.S. Pain Foundation, and a chronic pain patient herself,
“is enormously helpful to those of us who suffer chronic pain.” In a
chronic-pain support group Steinberg runs, she said that people find it a huge
affirmation to learn there’s a distinct biology underlying their pain. It
confirms what they’ve long known but often see doubted by doctors and friends:
That their pain is as real as any other.
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