Activation of alpha 2 adrenergic receptor of cerebrospinal fluid-contacting nucleus alleviates acute incision pain behavior in rats

Abstract Purpose Studies have shown that the cerebrospinal fluid(CSF) contacting nucleus plays a role in pain modulation. Dexmedetomidine (DEX), an alpha 2-adrenergic receptor agonist, has sedative, analgesic and anti-anxiety effects. In this study, we intend to investigate whether DEX can modulate acute incision pain by activating specific receptors on CSF-contacting neurons (CSF-CN) through lateral ventricular microinjection. Methods Cholera toxin B subunit (CB)- saporin (SAP) was injected into the lateral ventricle (LV) of rats to specifically damage CSF contacting nucleus and establish CSF-contacting nucleus “knockout” model animal. The model of acute incision pain was applied in rats, and mechanical allodynia and thermal hyperalgesia were adopted to evaluate the analgesic effect of DEX injected into LV. Further, to observe whether the CSF-contacting nucleus “knockout” could abate the analgesic effect of DEX. Immunofluorescence assay was used to detect the damage effect of CB-SAP on CSF-CN and the expression of alpha 2-adrenergic receptor in the CSFCN. The level of the second messenger cAMP in the CSF-CN was detected by ELISA. Results Immunofluorescence assay showed that 1 week after CB-SAP microinjection into the LV, the CSF-CN were completely damaged in rats, which successfully established the CSF contacting nucleus “knockout” rat model. Meanwhile, immunofluorescence confirmed the presence of alpha 2 adrenergic receptors in the neuron of CSF-contacting nucleus. Microinjection of dexmedetomidine into the LV could inhibit the pain behavior of rats in dose dependent manner, and the analgesic effect of DEX was significantly attenuated in CSF-contacting nucleus “knockout” rats. Conclusion Activation of alpha 2 adrenergic receptor of cerebrospinal fluid-contacting nucleus could modulate acute incision pain behavior in rats.