Touch and tactile neuropathic pain sensitivity are set by corticospinal projections
Open accessAbstract
Current models of somatosensory perception emphasize transmission from primary sensory neurons to the spinal cord and on to the brain 1-4. Mental influence on perception is largely assumed to occur locally within the brain. Here we investigate whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex. Although the corticospinal tract (CST) is traditionally viewed as a primary motor pathway 5, a subset of corticospinal neurons (CSNs) originating in the primary and secondary somatosensory cortex directly innervate the spinal dorsal horn via CST axons. Either reduction in somatosensory CSN activity or transection of the CST in mice selectively impairs behavioural responses to light touch without altering responses to noxious stimuli. Moreover, such CSN manipulation greatly attenuates tactile allodynia in a model of peripheral neuropathic pain. Tactile stimulation activates somatosensory CSNs, and their corticospinal projections facilitate light-touch-evoked activity of cholecystokinin interneurons in the deep dorsal horn. This touch-driven feed-forward spinal-cortical-spinal sensitization loop is important for the recruitment of spinal nociceptive neurons under tactile allodynia. These results reveal direct cortical modulation of normal and pathological tactile sensory processing in the spinal cord and open up opportunities for new treatments for neuropathic pain.
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The Prkcg dorsal excitatory family comprised Excit-3 and Excit-4 and likely corresponded to neurons involved in light static touch and allodynic pain in pathological situations.
“The Prkcg dorsal, excitatory family was comprised of Excit-3 and Excit-4 and likely corresponded to neurons involved in light static touch and allodynic pain in pathological situations46,48–56.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [54]
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- Authors
- Liu, Y., Latremoliere, A., Li, X., Zhang, Z., Chen, M., Wang, X., Fang, C., Zhu, J., Alexandre, C., Gao, Z., Chen, B., Ding, X., Zhou, J.-Y., Zhang, Y., Chen, C., Wang, K. H., Woolf, C. J., & He, Z.
- Affiliations
- Boston Children's Hospital (US)
- National Institutes of Health (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Wang, Kuan Hong
- Woolf, Clifford J.
- He, Zhigang
- ORCID
- Venue
- Nature
- Published
- 2018-09
- Volume
- 561
- Issue
- 7724
- Pages
- 547-550
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6163083
- OpenAlex
- W2890125899
- Cited by
- 276
- References
- 44
- Citations by year
- 2026: 21 · 2025: 49 · 2024: 35 · 2023: 46 · 2022: 35 · 2021: 37 · 2020: 27 · 2019: 24 · 2018: 2
- FWCI
- 15.44
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (Z01MH002897)
- National Eye Institute (P30EY012196)
- National Institute of Neurological Disorders and Stroke (R01NS096294, R01NS038253, R35NS105076)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD090255, P30HD018655)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Tactile and Sensory Interactions
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- corticospinal tract, corticospinal neurons, mechanical allodynia, neuropathic pain, tactile sensitivity, dorsal horn, cholecystokinin interneurons, nociceptive sensitization, somatosensory cortex, spinal nociceptive neurons
- MeSH terms
- Animals, Axons, Cholecystokinin, Female, Hindlimb, Hyperalgesia, Interneurons, Male, Neural Pathways, Neuralgia, Pyramidal Tracts, Somatosensory Cortex, Touch, Mice, Nociception, Spinal Cord Dorsal Horn
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