Pain in the Nervous System

How the Brain Handles Pain

Woman sitting on bed rubbing neck, eyes closed
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Treating chronic pain isn’t easy, and can be frustrating for both patients and physicians.  Pain is difficult to measure reliably, forcing doctors to rely on patients' descriptions, and there’s notoriously little relationship between subjective pain and actual tissue damage.  Some people feel almost no pain though their back looks terrible on X-rays, and others suffer from terrible back pain though their X-ray looks fine.

 

Still, helping people with pain has always been a priority for doctors.  For this reason, pain in the nervous system has been well-studied.  We know quite a bit about both how pain signals travel in the body, and how our body normally tries to control those signals.

Pain Signals In the Body

The body has certain nerves, called nociceptors, that send painful signals to the spinal cord.  There are different nerves for different types of pain—for example, one type sends information about sharp pain, and another about burning.  Pain fibers enter the spinal cord, where they may go up or down a level and synapse with other cells in the posterior horn.  From there they cross over to the other side of the cord, and run along the spinothalamic tract to the thalamus. 

The thalamus then relays painful information to the cerebral cortex.  There are multiple cortical areas that correlate with an individual’s subjective report of pain, including the anterior cingulate cortex, the somatosensory cortex, and the insula.

 Because there are multiple cortical areas that deal with pain, cortical damage doesn’t usually neutralize pain unless the lesion is very large.

Natural Pain Control

One of the best-known ways to control pain is with pain medications such as opiates.  In the 1970s, neuroscientists discovered that our body produces its own opiates, called endogenous opiates.

  This allows our body a degree of control over the amount of pain we feel.  The brain can send signals down the spinal cord to suppress pain signals traveling up the spine.

A strong example of how the brain controls pain can be demonstrated with a placebo, an inert substance such as a sugar pill that somehow has beneficial medicinal effects.  For example, in a study done with people whose wisdom teeth had just been pulled, placebos were able to provide a degree of pain control.  If given naloxone, a drug that blocks both endogenous and exogenous opiates, placebos can lose their effectiveness.  Functional MRI studies of people given placebos find changes in the hypothalamus, periaqueductal grey, and medulla, supporting the theory that these structures are involved with endogenous pain control.

Further research has shown that pain in the spinal cord involves two different types of cells, some of which are activated with pain and others that shut off.  Opiates turn on “off” cells, and pain stimulates “on” cells.

  This allows the brain to adjust our experience of pain even at the level of the spinal cord. 

How the Brain Controls Pain

The purpose of pain is to motivate us to escape injury, and to help us to learn to avoid situations likely to injure us in the future.  For example, if rats have a painful experience in a room, they’re more likely to avoid that room in the future.

That may sound simple enough, but often life forces us to make a decision about whether to ignore pain or to take action.  For example, if cheese is placed in a room where a rat has had an unpleasant experience, the animal has an internal conflict, and has to make a decision.  Understanding that decision helps us to understand chronic pain.

In 1984, researchers fed rats on a hot plate that was turned off.  Rats would either get regular rat chow or a chocolate covered graham cracker (which apparently rats enjoy).  After two weeks, the hot plate was turned on.  The rats, of course, jumped off.  The interesting thing is that the rats who got a chocolate covered graham cracker were slower to leave the hot plate—they would endure more pain in hopes of the reward.  Even more interesting was that the rats “mental toughness” went away entirely with naloxone, suggesting that endogenous opiates were what allowed them to tough it out on the hotplate in expectation of chocolate covered graham cracker goodness. 

The question remains, what in the brain allows the brain to make this decision of how to respond to pain?  What stimulates the brain to activate those endogenous opioids, and what causes the brain to respond to the pain and jump off the plate? 

The details are still being worked on, but briefly, response to pain, instead of activating the reward system, involves our limbic system—a region known to modulate learning and emotion. This is how we learn to avoid pain in the future.  Interestingly, neuroscientists have begun to find changes in these brain areas in people with chronic pain.  The hope is that with better understanding, new therapies may treat the pain at its true source, the brain, rather than continuing to hunt unsuccessfully for other causes.

Sources:  

Amanzio M, Benedetti F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. The Journal of neuroscience : the official journal of the Society for Neuroscience 1999;19:484-494.

Dum J, Herz A. Endorphinergic modulation of neural reward systems indicated by behavioral changes. Pharmacology, biochemistry, and behavior 1984;21:259-266.

Hughes J, Smith TW, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR. Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 1975;258:577-580.

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