Blockade of Spinal Dopamine D1/D2 Receptor Heteromers by -Corydalmine Suppressed Calcium Signaling Cascade in Spinal Neurons to Alleviate Bone Cancer Pain in Rats

Overview

Journal J Cancer

Specialty Oncology

Date 2024 Jan 17

PMID 38230224

Authors

Xiao-Nan Ma

Chang-Heng Yao

Yu-Jie Yang

Xue Li

Meng-Yuan Zhou

Jin Yang

Shen Zhang

Bo-Yang Yu

Wen-Ling Dai

Ji-Hua Liu

Affiliations

Soon will be listed here.

Abstract

Dopamine receptors have been reported to be involved in pain, while the exact effects and mechanism in bone cancer pain have not been fully explored. Bone cancer pain model was created by implanting walker 256 mammary gland carcinoma into right tibia bone cavity. Primary cultured spinal neurons were used for evaluation. FLIPR, western-blot, immunofluorescence, and Co-IP were used to detect cell signaling pathway. Our results indicated that spinal dopamine D1 receptor (D1DR) and spinal dopamine D2 receptor (D2DR) could form heteromers in TCI rats, and antagonizing spinal D1DR and D2DR reduced heteromers formation and alleviated TCI-induced bone cancer pain. Further results indicated that D1DR or D2DR antagonist induced antinociception in TCI rats could be reversed by D1DR, D2DR, and D1/D2DR heteromer agonists. And Gq, IP3, and PLC inhibitors also attenuated TCI-induced bone cancer pain. results indicated that D1DR or D2DR antagonist decreased the Ca oscillations upregulated by D1DR, D2DR, and D1/D2DR heteromer agonists in activated primary cultured spinal neurons. Moreover, inhibition of D1/D2DR heteromers induced antinociception in TCI rats was partially mediated by the CaMKII and MAPKs pathway. In addition, a natural compound -Corydalmine (CDL), could inhibit D1/D2DR heteromers and attenuate bone cancer pain. Inhibition of spinal D1/D2DR heteromers via CDL decreases excitability in spinal neurons, which might present new therapeutic strategy for bone cancer pain.

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