Neuropharmacology
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Cholinergic interneurons (ChIs) of dorsal striatum play a key role in motor control and in behavioural learning. Neuropeptides regulate cholinergic transmission and mu opioid receptor (MOR) activation modulates striatal acetylcholine release. However, the mechanisms underlying this effect are yet uncharacterized. ⋯ No cross-effect was observed, suggesting that the two receptors act independently. Our findings demonstrate a postsynaptic inhibitory modulation by MOR on ChIs excitability. Such opioidergic regulation of cholinergic transmission might contribute to shape information processing in basal ganglia circuits, and represent a potential target for pharmacological intervention.
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The majority of patients with metastatic bone disease experience moderate to severe pain. Bone cancer pain is usually progressive as the disease advances, and is very difficult to treat due to the poor understanding of the underlying mechanisms. Recent studies demonstrated that synaptic plasticity induces spinal cord sensitization and contributes to bone cancer pain. ⋯ In the present study, we showed that Protocadherin20 was significantly increased in the dorsal horn of cancer-bearing rats, while knockdown of Protocadherin20 with RNAi lentivirus reversed bone cancer-induced pain behaviors and decreased excitatory synaptogenesis in ipsilateral dorsal horn. In an in vitro study, we showed that knockdown of Protocadherin20 inhibited neurite outgrowth and excitatory synapse formation of dorsal neurons. These findings indicate that Protocadherin20 is required for the development of bone cancer pain probably by promoting the excitability synaptogenesis.