Beijing Friendship Hospital, China
Posters & Accepted Abstracts: Surgery Curr Res
Statement of the Problem: Neuroligin1 is an important synaptic cell adhesion molecule that modulates the function of synapses through protein-protein interactions. Yet, it remains unclear whether the regulation of synaptic transmission in the spinal cord by neruoligin1 contributes to the development of postoperative pain. Methodology: In a rat model of postoperative pain induced by plantar incision, we conducted Western blot study to examine changes in the expression of postsynaptic membrane of neuroligin1, postsynaptic density (PSD)-95, and α-amino-3-hydroxy5-methyl-4-isoxazole propionate (AMPA) receptor GluR1 and GluA2 subunits in the spinal cord dorsal horn after injury. The interaction between neuroligin1 and PSD-95 was further determined by using co-immunoprecipitation. Findings: Protein levels of neuroligin1 and GluR1, but not GluA2 and PSD-95, were significantly increased in the postsynaptic membrane of the ipsilateral dorsal horn at 3 h and one day after incision, as compared to that in control group (naïve). A greater amount of PSD-95 was co-immunoprecipitated with neuroligin1 at 3 h after incision than that in the control group. Intrathecal administration of small interfering RNAs (siRNAs) targeting neuroligin1 suppressed the expression of neuroligin1 in the spinal cord. Importantly, pretreatment with intrathecal neuroligin1 siRNA2497, but not scrambled siRNA or vehicle, prevented the upregulation of GluR1 expression at 3 h after incision, inhibited the enhanced neuroligin1/PSD-95 interaction, and attenuated postoperative pain. Conclusion & Significance: Current findings suggest that downregulation of spinal neuroligin1 expression may ameliorate postoperative pain through inhibiting neuroligin1/PSD-95 interaction and synaptic targeting of GluR1 subunit. Accordingly, spinal neuroligin1 may be a potential new target for postoperative pain treatment.
1. Kim J A, Kim D, Won S Y, Han K A, Park D, et al. (2017) Structural insights into modulation of neurexin-neuroligin trans-synaptic adhesion by MDGA1/Neuroligin-2 complex. Neuron 94(6): 121�??1131.
2. Wang Q, Li D, Bubula N, Campioni M R, McGehee D S, et al. (2017) Sensitizing exposure to amphetamine increases AMPA receptor phosphorylation without increasing cell surface expression in the rat nucleus accumbens. Neuropharmacology
3. Jeyifous O, Lin E I, Chen X, Antinone S E, Mastro R, et al. (2016) Palmitoylation regulates glutamate receptor distributions in postsynaptic densities through control of PSD95 conformation and orientation. Proc Natl Acad Sci. 113(52): E8482�??e8491.
4. Zhang B, Sudhof T C (2016) Neuroligins are selectively essential for NMDAR signaling in cerebellar stellate interneurons. J Neurosci. 36(35): 9070�??83.
5. Jedlicka P, Vnencak M, Krueger D D, Jungenitz T, Brose N, et al. (2015) Neuroligin-1 regulates excitatory synaptic transmission, LTP and EPSP-spike coupling in the dentate gyrus in vivo. Brain Struct Funct. 220(1): 47�??58.
Ruijuan Guo Attending doctor in Department of Anesthesiology, Beijing Friendship Hospital, Capital, Medical University, Beijing, China. Ph.D. at Capital Medical University, Beijing, China. Master of Medicine in Anesthesiology at Capital Medical University, Beijing, China. Bachelor of Medicine at Chengde Medical College, Hebei, China.