Role of 5-HT 2A Receptor in Modulating Glutamatergic Activity in the Ventrolateral Orbital Cortex: Implication in Trigeminal Neuralgia

• Published in: Neuroscience 2022-10, Vol.502, p.107
• Main Authors: Yuan, Shanshan, Wang, Na, Yao, Yunxia, Liu, Junhong, Gao, Mingwei, Mo, Hongbing, Zhang, Shuzhuo, Su, Ruibin
• Format: Article
• Language: English
• Subjects: Animals; Ketanserin - metabolism; Mice; Pain - metabolism; Prefrontal Cortex - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A - metabolism; RNA, Small Interfering - metabolism; Serotonin - metabolism; Trigeminal Neuralgia - metabolism
• ISSN: 1873-7544
• DOI: 10.1016/j.neuroscience.2022.08.018

5-HT receptors (5-HT Rs) are widely expressed in the central nervous system, including in the ventrolateral orbital cortex (VLO). The VLO is an important cortical component for pain processing. Brain 5-HT Rs are implicated in both pro- and anti- nociceptive functions. However, the roles of 5-HT Rs in the VLO in trigeminal neuralgia and neuronal synaptic function remain to be understood. We used chronic constriction injury of infraorbital nerve (IoN-CCI) model and shRNA mediated gene knockdown in mice to investigate the role of 5-HT Rs in the VLO in trigeminal neuralgia. We found that knockdown of 5-HT Rs in the VLO aggravated spontaneous pain and mechanical allodynia in mice after IoN-CCI. At the synaptic level, decreasing 5-HT R expression by shRNA or inhibition of 5-HT R activity by its antagonist ketanserin decreased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) of the neurons in the VLO, whereas 5-HT R partial agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI) enhanced sEPSCs of the neurons in the VLO. In summary, 5-HT Rs in the VLO modulate the trigeminal pain by regulating neuronal glutamatergic activity.