ZJU Scientists report a new circuit and molecular mechanisms underlying pain regulation

How is the feeling of pain generated? And what is our body going through when we are in pain? “Words are in vain when a patient is trying to describe the feeling to a doctor” said by Virginia Woolf, British author. Similarly, it remains a challenge for neuroscientists to come up with felicitous scientific mechanisms to help people understand pain.

Researchers from Prof. LI Xiaoming’s lab, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, have been dedicated to studies regarding emotions and behaviors for years with several breakthroughs achieved. A newly published research provides critical insights underlying pain by describing a new circuit and molecular mechanisms in detail. This research findings are published in Neuron, on June 4th. 

The novel research finding from LI’s Lab shows that when the body is subjected to pain-like traumatic stimulation, an alarming signal from the nerve endings reports it to the cerebral cortex via the circuit. Meanwhile, cannabinoids in a specific region of the thalamus blocks the upstream transmission of pain in this circuit, resulting inpain relieving. Further exploration of how the mechanisms underlying pain processing work as a whole brings much to be continued, which is what the LI's team has conducted regarding to this “black box”.

Previously, abnormal neural activity in both the zona incerta (ZI) and posterior complex of the thalamus (Po) are implicated in neuropathic pain, but their exact roles remain unclear. In particular, the precise cell-types involved and molecular mechanisms of the ZI-Po circuit that regulate nociception are largely uncharacterized.

The recent work identified that parvalbumin (PV)-positive neuronal projections from the ventral ZI (ZIv) to the Po (ZIv-Po) are critical for promoting pain behaviors, whereas selectively inhibiting ZIv-Po activity reduces painful sensory withdrawal responses.

(ZIv-Po circuit and CB1Rs expression in Po)

“This study is very comprehensive, using an impressive combination of different methodologies. The experiments were well designed, and executed with high quality. commented reviewers of Neuron. “The results are novel, revealing a new circuit of pain regulation and a potential central anatomical locus of cannabinoids analgesic action.”