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Papers of the Week

Papers: 29 Jun 2024 - 5 Jul 2024

2024 Jul 04

Mol Neurobiol


Activation of 5-HT Receptors in the Ventrolateral Orbital Cortex Produces Anti-Anxiodepressive Effects in a Rat Model of Neuropathic Pain.


Zhao YL, Yi HY, Baba SS, Guo YX, Yuan XC, Hou XM, Liang LL, Huo FQ


The comorbidity of anxiety and depression frequently occurs in patients with neuropathic pain. The ventrolateral orbital cortex (VLO) plays a critical role in mediating neuropathic pain and anxiodepression in rodents. Previous studies suggested that 5-HT receptors in the VLO are involved in neuropathic pain. Strong evidence supports a close link between 5-HT receptors and affective disorders such as depression and anxiety disorders. However, it remains unclear whether the 5-HT receptors in the VLO are involved in neuropathic pain-induced anxiodepression. Using a rat neuropathic pain model of spared nerve injury (SNI), we demonstrated that rats exhibited significant anxiodepression-like behaviors and the expression of VLO 5-HT receptors obviously decreased four weeks after SNI surgery. Microinjection of the 5-HT receptor agonist EMD-386088 into the VLO or overexpression of VLO 5-HT receptors alleviated anxiodepression-like behaviors. These effects were blocked by pre-microinjection of a selective 5-HT receptor antagonist (SB-258585) or inhibitors of AC (SQ-22536), PKA (H89), and MEK1/2 (U0126) respectively. Meanwhile, the expression of p-ERK, p-CREB, and BDNF in the VLO decreased four weeks after SNI surgery. Furthermore, administration of EMD-386088 upregulated the expression of BDNF, p-ERK, and p-CREB in the VLO of SNI rats, which were reversed by pre-injection of SB-258585. These findings suggest that activating 5-HT receptors in the VLO has anti-anxiodepressive effects in rats with neuropathic pain via activating AC-cAMP-PKA-MERK-CREB-BDNF signaling pathway. Accordingly, 5-HT receptor in the VLO could be a potential target for the treatment of the comorbidity of neuropathic pain and anxiodepression.