NOV 19, 2018 11:47 PM PST

Researchers identify neural pathways that control behavioral responses to noxious stimuli

Behavioral responses to the pain could range from the reflexive withdrawal to more complex behaviors to avoid or decrease the pain. Neurons in the lateral division of the parabrachial nucleus (PBNI) are deemed to be the primary responders to various noxious stimuli. However, information on the subtypes of neurons within the PBNI that respond to pain have not yet been explored.

View this video that animates the five phases of nociceptive pain.

Decerbrated preclinical animal studies showed that supra-spinal hindbrain circuits also play a critical role in pain perception. As with the PBNI, neuronal substrates within this circuit, that individually respond to noxious stimuli remain unknown.

Image Credit: SUN Yangang's lab, University of Chinese Academy of Sciences, China

Study published in Neuron by researchers from the National Center for Complementary and Integrative Health (NCCIH), an intramural division of NIH, identified a small group of Tachykinin(Tac-1) positive neurons in PBNI, that receive monosynaptic input from the dorsal spinal cord and make excitatory connections with the dorsal reticular formation in the medulla (MdD) in response to noxious heat stimuli.

 “Much is known about local spinal cord circuits for simple reflexive responses, but the mechanisms underlying more complex behaviors remain poorly understood,” said Alexander T. Chesler, Ph.D., a Stadtman Investigator at NCCIH and senior author of the study. “We set out to describe the brain pathway that controls motor responses and involuntary behaviors when the body is faced with painful experiences.”

The gene Tac1 encodes tachykinin peptide hormones, which are known to induce behavioral responses and function as vasodilators and secretagogues.  Racing of the neurons within PBNI showed their projections to MdD. Further chemogenetic activation of PBNI neurons using DREADD in 6 mice showed that when presented with noxious heat stimulus, escape like jumping behavior was seen. This response was absent when the heat below pain threshold was introduced confirming the role of PBNI neurons in painful somatosensory signaling.

Further, ablation of the PBNI Tac1 neurons showed no jumping behavior in response to a painful heat stimulus. Tracing of the PBNI Tac1 neurons also revealed that they receive input from two primary anterograde targets, MdD and central nucleus of the amygdala (CeA) with MdD as the most crucial target. Additionally, a subset of Tac1 expression neurons was also found in MdD with protections to dorsal spinal cord and PBN. Together, PBNI and MdD Tac1 neurons create a pronociceptive Tac1 brainstem-spinal circuit that regulates the behavioral responses to noxious stimulus.

 “Our data provide evidence that the PBNI produces streams of information with distinct functional significance,” said Arnab Barik, Ph.D., a postdoctoral fellow at NCCIH and one of the study’s authors. “The brainstem-spinal cord pathway identified in this study selectively controls pain response and elicits appropriate behaviors based on sensory input.”

Added Chesler, “This kind of feed-forward circuitry is unique because it is an upward spiral. The more this pathway is activated by harmful activity, the more it reacts, leading to dramatic behavioral responses.”

These findings are just the tip of the iceberg. Tac1 expressing neurons might be the gatekeepers but how this information trickles down to complex behavioral responses in the presence of other biological demands warrants more research. Understanding these complex pain pathways might help us understand how homeostasis is affected during chronic pain.

Sources: Neuron, Neuroscience News

About the Author
  • Aswini Kanneganti is an experienced research scientist from Dallas, Texas. Her interests include neuroscience, medical devices, and neuromodulation.
You May Also Like
SEP 20, 2019
Drug Discovery & Development
SEP 20, 2019
Anticholinergic Drugs and Dementia?
A link between anticholinergic drug use and cognitive impairment was recently observed from observational studies on randomized clinical trials. Regenstrie...
SEP 20, 2019
Genetics & Genomics
SEP 20, 2019
Anorexia is Caused by Genetics and Gut Bacteria
Although usually considered a purely psychiatric disorder, recent research has uncovered that anorexia nervosa may have other underlying causes. From genet...
SEP 20, 2019
Genetics & Genomics
SEP 20, 2019
Motor Neurone Disease is 52% Genetic
In a new study, researchers at Trinity College Dublin have found 1 in every 347 men and 1 in every 436 women are likely to develop motor neurone disease (M...
SEP 20, 2019
Health & Medicine
SEP 20, 2019
New drug to treat opioid use disorder during pregnancy is favorable for mom, and baby
On average, a baby is born in withdrawal from opioids every 15 minutes in the U.S., according to recent research. Opioid use during pregnancy can result in...
SEP 20, 2019
Technology
SEP 20, 2019
Online Brain Games Enable 'Cognitive Youth'
A recent study by researchers in the University of California, Irvine—have found that online brain game activities have a positive effect on extendin...
SEP 20, 2019
Drug Discovery & Development
SEP 20, 2019
Does Adderall Really Work for People without ADHD?
Adderall is a popular stimulant. Known to treat Attention Deficit Disorder (ADHD), those without the condition also use it to increase attention, focus and...
Loading Comments...