Central control of opioid-induced mechanical hypersensitivity (OIH) and tolerance in mice
The researchers found that intra-PBN injection of morphine or DAMGO paradoxically induces bilateral morphine-resistant mechanical pain hypersensitivity instead of relieving mechanical pain.
Further, they identified a brain-to-spinal opioid pathway that controls morphine-induced mechanical OIH and analgesic tolerance.
The pathway stars 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), and 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).
Targeting this opioid pathway rescued repetitive systemic morphine-induced mechanical OIH/tolerance in mice.
