| First Author | Yin G | Year | 2024 |
| Journal | Neuron | PubMed ID | 39406237 |
| Mgi Jnum | J:358141 | Mgi Id | MGI:7779506 |
| Doi | 10.1016/j.neuron.2024.09.014 | Citation | Yin G, et al. (2024) Central control of opioid-induced mechanical hypersensitivity and tolerance in mice. Neuron |
| abstractText | Repetitive use of morphine (MF) and other opioids can trigger two major pain-related side effects: opioid-induced hypersensitivity (OIH) and analgesic tolerance, which can be subclassified as mechanical and thermal. The central mechanisms underlying mechanical OIH/tolerance remain unresolved. Here, we report that a brain-to-spinal opioid pathway, starting from mu-opioid receptor (MOR)-expressing neuron in the lateral parabrachial nucleus (lPBN(MOR+)) via dynorphin (Dyn) neuron in the paraventricular hypothalamic nucleus (PVH(Dyn+)) to kappa-opioid receptor (KOR)-expressing GABAergic neuron in the spinal dorsal horn (SDH(KOR-GABA)), controls repeated systemic administration of MF-induced mechanical OIH and tolerance in mice. The above effect is likely mediated by disruption of dorsal horn gate control for MF-resistant mechanical pain via silencing of the Dyn-positive GABAergic neurons in the SDH (lPBN(MOR+) --> PVH(Dyn+) --> SDH(KOR-GABA) --> SDH(Dyn-GABA)). Repetitive binding of MF to MORs during repeated MF administration disrupted the above circuits. Targeting the above brain-to-spinal opioid pathways rescued repetitive MF-induced mechanical OIH and tolerance. |
