Central control of opioid-induced mechanical hypersensitivity and tolerance in mice

Authors
Guangjuan Yin, Kaifang Duan, Dong Dong, Feng Du, Chao Guo, Changyi Zhang, Xi Liu, Yuanjie Sun, Tianwen Huang, Guangfu Cui, Longzhen Cheng


Lab

Journal
Neuron

Abstract

Summary

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 -opioid receptor (MOR)-expressing neuron in the lateralparabrachial nucleus (lPBNMOR+) via dynorphin (Dyn) neuron in the paraventricular hypothalamic nucleus (PVHDyn+) to k-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+ to SDHKOR-GABA to 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.

Keywords/Topics
opioid; morphine; OIH; analgesic tolerance ;mechanical MOR ;Dyn KOR ;parabrachial nucleus; hpothalamus

BIOSEB Instruments Used:
Cold Hot Plate Test (BIO-CHP)

Source :

https://www.cell.com/neuron/fulltext/S0896-6273(24)00662-7?uuid=uuid%3Aef882ba8-20b1-48fd-9a88-b3280b700cf9

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