Mapping the Pathway of Pain

What causes our response to pain?


What makes us pull a hand away from a hot stove or flinch at a pinprick? Researchers from the National Center for Complementary and Integrative Health say they have identified activity in the brain that governs these reactions.

Alexander Chesler, PhD, senior author of the study, says we already know a lot about local spinal cord circuits for simple reflexive responses, but “the mechanisms underlying more complex behaviors remain poorly understood.”

Using heat as the source of discomfort in their experiments, the researchers found a predictable sequence of behaviors—likened to the sequence of responding to walking cautiously on a hot beach, then hopping as the heat intensifies, then running to a water source. “This kind of ‘feed-forward’ circuitry is unique because it is an upward spiral,” says Arnab Barik, PhD, one of the study authors. “The more this pathway is activated by harmful activity, the more it reacts, leading to dramatic behavioral responses.”

The experiments showed that the parts of the brainstem involved in this circuit are the parabrachial nucleus (PBNI) and the dorsal reticular formation in the medulla (MdD). Standing on a hot surface activated a group of nerve cells in the PBNI, triggering escape responses through connections to the MdD. Interestingly, the PBNI cells express a gene that codes for substances that also contribute to multiple disease processes.

“Our data provide evidence that the PBNI produces streams of information with distinct functional significance,” says Arnab Barik, PhD, one of the study authors. “The brainstem-spinal cord pathway identified in this study selectively controls pain response and elicits appropriate behaviors based on sensory input.”

Further investigation, the researchers say, can help us understand how pain is encoded in the brain. The study findings may also offer opportunities to understand how the body becomes dysregulated during chronic pain.

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