Imbalance of nociceptive homeostasis drives spinal cord injury pain
Exp Neurol. 2026 Apr 16:115786. doi: 10.1016/j.expneurol.2026.115786. Online ahead of print.
ABSTRACT
Somatosensory synaptic transmission is an adapting phenomenon according to changes of synaptic environments composed of neurons and glial cells. Synaptic architecture in the spinal dorsal horn well recognizes and identifies sensory modalities, such as nociceptive and non-nociceptive, however, sensory neurons do not identify only single modality, therefore, synaptic transmission is dynamic and phasic events. More importantly, maladaptive synaptic plasticity developed chronically and critically drives the new setup of synaptic environments that results in enhanced or decreased synaptic transmission, which is called loss of synaptic homeostasis or newly developed synaptic homeostasis. Overall, the synaptic homeostasis critically controls distinct painful and non-painful sensory signals from peripheral to the higher nervous system via the discrimination of sensory modality. After neurotrauma, such as spinal cord injury, new set of synaptic environments reveal the tendency of excitatory signaling rather than inhibitory and directly correlated with neuropathic pain-like behaviors (hypersensitivity) with enhanced neuronal activity (hyperexcitability) in the spinal dorsal horn neurons. A newly developed imbalance of excitatory and inhibitory persists rather than returning to normal and contributing to the development of sensorimotor, cognition, motivation, and chronic pain. Taken together, understanding the imbalance between excitatory and inhibitory in synaptic transmission is essential to develop the therapeutic strategy for SCI pathophysiology. In this review, we address the basic mechanism to how SCI leads to the imbalance of excitatory and inhibitory followed by development of new synaptic environments in the injured spinal dorsal horn that results in chronic neuronal hyperexcitability and neuropathic pain.
PMID:41999832 | DOI:10.1016/j.expneurol.2026.115786