Identification of spinal circuits involved in touch-evoked dynamic mechanical pain
Open accessAbstract
Mechanical hypersensitivity is a debilitating symptom for millions of chronic pain patients. It exists in distinct forms, including brush-evoked dynamic and filament-evoked punctate hypersensitivities. We reduced dynamic mechanical hypersensitivity induced by nerve injury or inflammation in mice by ablating a group of adult spinal neurons defined by developmental co-expression of VGLUT3 and Lbx1 (VT3 Lbx1 neurons): the mice lost brush-evoked nocifensive responses and conditional place aversion. Electrophysiological recordings show that VT3 Lbx1 neurons form morphine-resistant polysynaptic pathways relaying inputs from low-threshold Aβ mechanoreceptors to lamina I output neurons. The subset of somatostatin-lineage neurons preserved in VT3 Lbx1-neuron-ablated mice is largely sufficient to mediate morphine-sensitive and morphine-resistant forms of von Frey filament-evoked punctate mechanical hypersensitivity. Furthermore, acute silencing of VT3 Lbx1 neurons attenuated pre-established dynamic mechanical hypersensitivity induced by nerve injury, suggesting that these neurons may be a cellular target for treating this form of 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 [51]
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References 59 · Cited by 240
- Authors
- Cheng, L., Duan, B., Huang, T., Zhang, Y., Chen, Y., Britz, O., Garcia-Campmany, L., Ren, X., Vong, L., Lowell, B. B., Goulding, M., Wang, Y., & Ma, Q.
- Affiliations
- Harvard University (US)
- Wannan Medical College (CN)
- Fudan University (CN)
- Salk Institute for Biological Studies (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Wang, Yun
- Ma, Qiufu
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2017-04-24
- Volume
- 20
- Issue
- 6
- Pages
- 804-814
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5470641
- OpenAlex
- W2609684457
- Cited by
- 240
- References
- 59
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 36 · 2023: 23 · 2022: 37 · 2021: 19 · 2020: 22 · 2019: 29 · 2018: 21 · 2017: 3
- FWCI
- 15.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057521, R01DK075632, R01DK089044, P30DK046200, R01DK111401, R01DK096010)
- National Institute of Neurological Disorders and Stroke (P01NS072040, R01NS086372, P30NS072031)
- National Institute of Dental and Craniofacial Research (R01DE018025)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- mechanical hypersensitivity, VGLUT3, Lbx1, neuropathic pain, somatostatin neurons, lamina I, nerve injury, place aversion, gene ablation, chronic pain
- MeSH terms
- Action Potentials, Animals, Avoidance Learning, Clozapine, Diphtheria Toxin, Female, Hyperalgesia, Male, Mice, Transgenic, Morphine, Muscle Proteins, Neural Pathways, Neurons, Pain Measurement, Somatostatin, Spinal Cord, Touch, Amino Acid Transport Systems, Acidic, Nerve Fibers, Unmyelinated, Mice, Gene Knock-In Techniques, Heparin-binding EGF-like Growth Factor
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