Differential modification of ascending spinal outputs in acute and chronic pain states
Year: 2025
Type: article
Abstract: Pain hypersensitivity arises from the plasticity of peripheral and spinal somatosensory neurons, which modifies nociceptive input to the brain and alters pain perception. We utilized chronic calcium imaging of spinal dorsal horn neurons to determine how the representation of somatosensory stimuli in the anterolateral tract, the principal pathway transmitting nociceptive signals to the brain, changes between distinct pain states. In healthy conditions, we identify stable, narrowly tuned outputs selective for cooling or warming, and a neuronal ensemble activated by intense/noxious thermal and mechanical stimuli. Induction of an acute peripheral sensitization with capsaicin selectively and transiently retunes nociceptive output neurons to encode low-intensity stimuli. In contrast, peripheral nerve injury-induced neuropathic pain results in a persistent suppression of innocuous spinal outputs coupled with activation of a normally silent population of high-threshold neurons. These results demonstrate the differential modulation of specific spinal outputs to the brain during nociceptive and neuropathic pain states.
Source: Neuron
Institutions: Boston Children's Hospital, Harvard University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Boston Children's Hospital, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, National Eye Institute, National Center for Complementary and Alternative Medicine, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Center for Complementary and Integrative Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G3000399083, G3830015915, Spinal Cord Nociceptive Circuits that Deliver Outputs to the Brain to Initiate Pain, G5923282642, Defining the generators of spontaneous trigeminal pain, G9000200862, Boston Children's Hospital/HMS Intellectual and Developmental Disabilities Research Center, Unravelling Mechanisms and Novel Therapeutic Targets for Peripheral Neuropathy and Neuropathic Pain, CORE GRANT FOR VISION RESEARCH
OpenAlex ID: W4408028207