神経科学研究部 訪問研究員の山本純偉です。以下の論文を紹介します。よろしくお願いいたします。
Central control of opioid-induced mechanical hypersensitivity and tolerance in mice.
Yin G, Duan K, Dong D, Du F, Guo C, Zhang C, Liu X, Sun Y, Huang T, Cui G, Cheng L.
Neuron. 2024 Dec 4;112(23):3897-3923.e10. doi: 10.1016/j.neuron.2024.09.014. Epub 2024 Oct 14.PMID: 39406237
Abstract
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 μ-opioid receptor (MOR)-expressing neuron in the lateral parabrachial nucleus (lPBNMOR+) via dynorphin (Dyn) neuron in the paraventricular hypothalamic nucleus (PVHDyn+) to κ-opioid receptor (KOR)-expressing GABAergic neuron in the spinal dorsal horn (SDHKOR-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 (lPBNMOR+ → PVHDyn+ → SDHKOR-GABA → SDHDyn-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.