Dexmedetomidine Ameliorates Pain-Depression Comorbidity and Downregulates TAZ Expression in Spinal Microglia in Rats

Han ZENG; Can AN; Wenfeng LI; Mingyuan LIU; Shixiang ZHAO; Zhigui LI; Jiayu CHEN; Na LI

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Article Navigation > Journal of Kunming Medical University > 2026 > Accepted Manuscript

Han ZENG, Can AN, Wenfeng LI, Mingyuan LIU, Shixiang ZHAO, Zhigui LI, Jiayu CHEN, Na LI. Dexmedetomidine Ameliorates Pain-Depression Comorbidity and Downregulates TAZ Expression in Spinal Microglia in Rats[J]. Journal of Kunming Medical University.

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Dexmedetomidine Ameliorates Pain-Depression Comorbidity and Downregulates TAZ Expression in Spinal Microglia in Rats

1.
School of Clinical Medicine，Dali University，Dali Yunnan 671003
2.
Graduate School，Kunming Medical University ，Kunming Yunnan 650500
3.
Department of Anesthesiology，920th Hospital of Joint Logistics Support Force，Kunming Yunnan 650032
4.
Department of Orthopedics，The First People's Hospital of Yunnan Province，Kunming Yunnan 650032，China

Received Date: 2026-04-27

Abstract

Abstract

Objective To investigate whether dexmedetomidine （DEX） improves neuropathic pain （NP） and comorbid depression, and whether changes in spinal dorsal horn microglial activation and TAZ expression after DEX treatment occur in parallel with behavioral improvement. Methods A rat model of NP–depression comorbidity was established using chronic constriction injury （CCI） of the sciatic nerve. Rats were divided into a sham-operated group （Sham, n = 9）, a model group （CCI, n = 27）, and a post-modeling DEX treatment group （CCI+DEX, n = 27）. The CCI+DEX group received daily intramuscular DEX （80 μg/kg） from surgery to day 13. Mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） were measured before surgery and on postoperative days 3, 7, and 14 to assess pain. Forced swim test （FST）, open field test （OFT）, and sucrose preference test （SPT） were performed on postoperative days 7 and 14 to assess depression-like behavior. Immunofluorescence and Western blotting were used to assess Iba1 （a microglial marker） in the spinal dorsal horn, and immunofluorescence was used to assess TAZ expression. Results Compared with the Sham group, CCI rats showed reduced postoperative MWT[Sham day 3 （13.89±2.2） g; Sham day 7 （14.44±1.67） g; Sham day 14 （12.56±2.96） g; CCI day 3 （7.83±0.98） g; CCI day 7 （5.11±1.05） g; CCI day 14 （2.20±1.39） g] （P < 0.0001）, shortened TWL [Sham day 3 （12.07±1.11） s; Sham day 7 （12.45±0.75） s; Sham day 14 （12.69±0.82） s; CCI day 3 （8.77±0.65） s; CCI day 7 （7.72±1.47） s; CCI day 14 （7.67±0.78） s] （P < 0.0001）, decreased sucrose preference [Sham day 14 （0.77±0.05）; CCI day 14 （0.58±0.13）] （P < 0.0001）, prolonged immobility time in the FST [Sham day 14 （34±5.50） s; CCI day 14 （60.33±9.21） s] （P < 0.001）, and fewer entries into the center zone in the OFT [Sham day 14 （7.44±1.51）; CCI day 14 （3.78±1.39）] （P < 0.0001）, indicating successful model establishment. Compared with the CCI group, the DEX-treated group showed increased MWT [CCI day 3 （7.83±0.98） g; CCI day 7 （5.11±1.05） g; CCI day 14 （2.20±1.39） g; CCI+DEX day 3 （12.79±1.42） g; CCI+DEX day 7 （8.44±1.67） g; CCI+DEX day 14 （8.22±2.33） g] and TWL [CCI day 3 （8.77±0.65） s; CCI day 7 （7.72±1.47） s; CCI day 14 （7.67±0.78） s; CCI+DEX day 3 （9.96±1.54） s; CCI+DEX day 7 （10.08±0.92） s; CCI+DEX day 14 （10.51±1.11） s] （both P < 0.001）, increased sucrose preference [CCI day 14 （0.58±0.13）; CCI+DEX day 14 （0.71±0.08）] （P < 0.05）, reduced immobility time [CCI day 14 （60.33±9.21） s; CCI+DEX day 14 （47.89±5.53） s] （P < 0.05）, and more entries into the center zone [CCI day 14 （3.78±1.39）; CCI+DEX day 14 （6.22±1.39）] （P < 0.01）. Immunofluorescence showed that expression of Iba1 [Sham （1±0.34）; CCI day 14 （3.01±0.46）] and TAZ [Sham （1.0±0.20）; CCI day 3 （4.96±2.82）] in the spinal dorsal horn was significantly increased in the CCI group （P < 0.001 or P < 0.0001）. TAZ expression peaked on postoperative day 3, whereas Iba1 expression continued to increase through day 14. After DEX treatment, expression of both Iba1 [CCI day 14 （3.01±0.46）; CCI+DEX day 14 （1.41±0.59）] （P < 0.01） and TAZ [CCI day 3 （4.96±2.82）; CCI+DEX day 3 （2.09±0.45）] （P < 0.001） was significantly reduced. Conclusion Dexmedetomidine improves pain and depressive-like behavior in CCI rats, accompanied by inhibition of microglial activation and downregulation of TAZ expression in the spinal dorsal horn. The early increase of TAZ may participate in microglia-driven neuroinflammatory process, and the effects of DEX may be related to regulation of TAZ.

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