Intrathecal Injection of GRIP-siRNA Reduces Postoperative Synaptic Abundance of Kainate Receptor GluK2 Subunits in Rat Dorsal Horns and Pain Hypersensitivity.

Abstract

The mechanisms underlying postoperative pain differ from the inflammatory or neuropathic pain. Previous studies have demonstrated that intrathecal α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) -kainate (KA) receptor antagonist inhibits the guarding pain behavior and mechanical hyperalgesia, indicating a critical role of spinal KA receptors in postoperative pain hypersensitivity. However, how the functional regulations of spinal KA receptor subunits are involved in the postoperative pain hypersensitivity remains elusive. Therefore, in the current study, we investigated the synaptic delivery of spinal KA receptor subunits and the interaction between KA receptor subunits and glutamate receptor-interacting protein (GRIP) during the postoperative pain. Our data indicated that plantar incision induced the synaptic delivery of GluK2, but not GluK1 or GluK3 in ipsilateral spinal cord dorsal horns. The co-immunoprecipitation showed an increased GluK2 -GRIP interaction in ipsilateral dorsal horn neurons at 6 h post-incision. Interestingly, Intrathecal pretreatment of GRIP siRNA increased the paw withdrawal thresholds to mechanical stimuli and decreased the cumulative pain scores in the paws ipsilateral to the incision at 6 h post-incision. Additionally, Intrathecal pretreatment of GRIP siRNA reduced the synaptic abundance of GluK2 in ipsilateral spinal dorsal horn at 6 h after plantar incision. In general, our data have demonstrated that the GluK2- GRIP interaction-mediated synaptic abundance of GluK2 in dorsal horn neurons plays an important role in the postoperative pain hypersensitivity. Disrupting the GluK2- GRIP interaction may provide a new approach for relieving postoperative pain.

• Authors: Ruijuan Guo, Huili Li, Rong Shi, Yun Wang
• Journal: Neurochemical research (Neurochem Res) Vol. 46 Issue 7 Pg. 1771-1780 (Jul 2021) ISSN: 1573-6903 [Electronic] United States
• PMID: 33847855 (Publication Type: Journal Article)

Chemical References

• Grip1 protein, rat
• Intracellular Signaling Peptides and Proteins
• Nerve Tissue Proteins
• RNA, Small Interfering
• Receptors, Kainic Acid

Topics

• Animals
• Dermatologic Surgical Procedures
• Down-Regulation (drug effects)
• Foot (surgery)
• Forelimb (surgery)
• Injections, Spinal
• Intracellular Signaling Peptides and Proteins (metabolism)
• Nerve Tissue Proteins (metabolism)
• Pain, Postoperative (drug therapy)
• Posterior Horn Cells (drug effects, metabolism)
• RNA, Small Interfering (administration & dosage, therapeutic use)
• Rats
• Receptors, Kainic Acid (metabolism)
• Skin (drug effects)
• Spinal Cord Dorsal Horn (cytology, metabolism)
• Synapses (drug effects, metabolism)
• GluK2 Kainate Receptor