A pathway from midcingulate cortex to posterior insula gates nociceptive hypersensitivity

• Published in: Nature neuroscience Vol. 20; no. 11; pp. 1591 - 1601
• Main Authors: Tan, Linette Liqi, Pelzer, Patric, Heinl, Céline, Tang, Wannan, Gangadharan, Vijayan, Flor, Herta, Sprengel, Rolf, Kuner, Thomas, Kuner, Rohini
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2017; Nature Publishing Group
• Subjects: 13/1; 13/51; 14/19; 631/378/3920; 692/699/375/1692; 9/30; 9/74; Afferent Pathways - chemistry; Afferent Pathways - pathology; Afferent Pathways - physiology; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedicine; Cerebral Cortex - chemistry; Cerebral Cortex - pathology; Cerebral Cortex - physiology; Cingulate cortex; Circuits; Conditioning; Cortex (cingulate); Cortex (somatosensory); Cortex (temporal); Gyrus Cinguli - chemistry; Gyrus Cinguli - pathology; Gyrus Cinguli - physiology; Hypersensitivity; Male; Medical examination; Mice; Mice, Inbred C57BL; Neural circuitry; Neurobiology; Neurosciences; Nociception; Optogenetics - methods; Organ Culture Techniques; Pain; Pain - pathology; Pain - physiopathology; Pain Measurement - methods; Pain perception; Physiological aspects; Sensory neurons; Spinal cord
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.4645

The authors identify the midcingulate cortex as a region that gates nociceptive plasticity without modulating basal nociception or the affective component of acute pain in mice. They identify a novel pathway from the midcingulate cortex to the posterior insula that recruits descending serotonergic projections to facilitate nociception. The identity of cortical circuits mediating nociception and pain is largely unclear. The cingulate cortex is consistently activated during pain, but the functional specificity of cingulate divisions, the roles at distinct temporal phases of central plasticity and the underlying circuitry are unknown. Here we show in mice that the midcingulate division of the cingulate cortex (MCC) does not mediate acute pain sensation and pain affect, but gates sensory hypersensitivity by acting in a wide cortical and subcortical network. Within this complex network, we identified an afferent MCC–posterior insula pathway that can induce and maintain nociceptive hypersensitivity in the absence of conditioned peripheral noxious drive. This facilitation of nociception is brought about by recruitment of descending serotonergic facilitatory projections to the spinal cord. These results have implications for our understanding of neuronal mechanisms facilitating the transition from acute to long-lasting pain.