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Published on: July 16, 2014
Pharmacological Inhibition of Tropomyosin Receptor Kinase B Reverses Remifentanil-Induced Postoperative Hyperalgesia
Lijun Yang1, Yu Huang1, Bo Long2
1Department of Anesthesiology,Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, People's Republic of China.
Purpose:
This study investigated the contributions of tropomyosin receptor kinase B (TrkB) signaling to behavioral hyperalgesia and associated spinal synaptic and dendritic remodeling in the rat remifentanil-induced hyperalgesia (RIH) model.
Methods:
Forty rats were randomly assigned to four treatment groups (n = 10/group): normal saline + TrkB inhibitor (NS + ANA), surgical incision of the hind paw (I), remifentanil + incision (IR), and remifentanil + incision + TrkB inhibitor (IR + ANA). Paw mechanical withdrawal threshold (PMWT), expression levels of Brain-derived neurotrophic factor (BDNF), TrkB, and synaptic proteins, and dendritic morphology were compared among groups.
Results:
Rats in the IR group exhibited significantly reduced mechanical pain thresholds and elevated expression levels of BDNF, TrkB, the glutamate receptor 1 subunit (GluR1), postsynaptic density protein 95 (PSD-95), and synapsin compared to the I group at 48 h post-surgery. In addition, IR rats had longer spinal dendrites with greater branching complexity. Administration of a TrkB inhibitor (IR + ANA group) reversed all these changes, with the exception of upregulated BDNF expression.
Conclusion:
This study provides molecular and morphological evidence that TrkB inhibition reverses synaptic structural remodeling in RIH, suggesting TrkB as a potential therapeutic target. The feasibility of TrkB inhibitors for human postoperative hyperalgesia warrants further investigation.
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