The cast immobilization induces sensory hypersensitivity via upregulation of postsynaptic dopamine D2 receptors in the nucleus accumbens of rats

Yukie kawahara, Yuki Kishikawa, Yoshinori Ohnishi, Naoki Sotogaku, Tomoko Koeda, Hiroshi Kawahara, Akinori Nishi
Purpose:

Despite the importance of the mesolimbic dopamine system in chronic pain, there is no direct evidence of altered dopamine neurotransmission in the NAc under immobilization-induced hypersensitivity. Therefore, we investigated the role of dopamine neurotransmission in the NAc of rats with chronic cast immobilization. 

Methods:

The present study investigated the role of dopamine neurotransmission in the NAc of rats with cast immobilization-induced mechanical hypersensitivity using in vivo microdialysis. In addition, we performed real-time PCR to confirm the upregulation of D2 receptors in the nucleus accumbens.

Results:

Mechanical stimulation of the cast-immobilized hind limb induced a decrease in dopamine in the NAc, and this decrease was mediated through the upregulation of presynaptic D2 receptors. A D2 receptor antagonist infused into the NAc reversed the decrease in PWT in rats with cast immobilization, whereas a D2 receptor agonist infused into the NAc induced a decrease in PWT in control rats. In addition, the expression of the D2 receptor (Drd2) mRNA in the NAc was increased by cast immobilization. Importantly, systemic administration of the D2 receptor antagonist reversed the decrease in PWT in rats with cast immobilization. 

Conclusion(s):

These results suggest that immobilization-induced mechanical hypersensitivity is attributable to the upregulation of postsynaptic D2 receptors in the NAc. 

Implications:

Blockade of D2 receptors in the NAc is a potential therapeutic strategy for immobilization-induced hypersensitivity.

Funding acknowledgements:
This research was supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (Grant Number: 21K17465).
Keywords:
Hyperalgesia
D2 receptor
Microdialysis
Primary topic:
Neurology
Second topic:
Pain and pain management
Third topic:
Basic science including molecular and cellular health
Did this work require ethics approval?:
Yes
Name the institution and ethics committee that approved your work:
The protocols were approved by the Institutional Animal Care and Use Committee of Kurume University School of Medicine.
Provide the ethics approval number:
2021-015
Has any of this material been/due to be published or presented at another national or international conference prior to the World Physiotherapy Congress 2025?:
No

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