Previous studies have shown that oral administration of NMDAR modulators NYX-2925 reduces pain in several animal models of neuropathic pain and this appears to be through Mpfc, but no spine, mediated mechanism. While much is known about the impact of neuropathic pain in NMDAR-mediated signaling in the spinal cord, limited studies have focused on the brain. In the current study, we estimate indicates changes associated with NMDAR-mediated plasticity in Mpfc and impact of NYX-2925 administration on normalization of the signal changes.
We found decreased levels of Src Mpfc activated in animals with chronic constriction injury (CCI) of the sciatic nerve.
While Src-mediated activation of NMDARs also decreased in animals CCI, major phosphorylation sites CAMKII NMDAR not affected. This is contrary to what has been found in the spinal cord, where both Src and activation CAMKII increased. NYX oral-2925 restored the level of Src and Src phosphorylation sites enabled on GluN2A and GluN2B in Mpfc, with no effect on the level of CAMKII activated. Analgesic effect of NYX-2925 appears dependent on activation of Src in this recovery Mpfc, as co-organizer of Src inhibitor prevents activation of NYX-2925 analgesic effect.
The NMDAR modulator NYX-2925 alleviates neuropathic pain via a Src-dependent mechanism in the mPFC.
Overall, these data suggest that NMDAR-mediated signaling plays a key role in neuropathic pain, although in a different direction in the spinal cord vs Mpfc. Additionally, the analgesic effect of NYX-2925 appears to involve the recovery of NMDAR-mediated signaling in Mpfc.
Buffer: Preservative: 0.03% Proclin 300 Constituents: 50% Glycerol, 0.01M PBS, PH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against TUBAL3. Recognizes TUBAL3 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IHC; Recommended dilution: IHC:1:20-1:200
Buffer: Preservative: 0.03% Proclin 300 Constituents: 50% Glycerol, 0.01M PBS, PH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against TUBAL3. Recognizes TUBAL3 from Human. This antibody is HRP conjugated. Tested in the following application: ELISA
Buffer: Preservative: 0.03% Proclin 300 Constituents: 50% Glycerol, 0.01M PBS, PH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against TUBAL3. Recognizes TUBAL3 from Human. This antibody is FITC conjugated. Tested in the following application: ELISA
Buffer: Preservative: 0.03% Proclin 300 Constituents: 50% Glycerol, 0.01M PBS, PH 7.4 >95%, Protein G purified
Description: A polyclonal antibody against TUBAL3. Recognizes TUBAL3 from Human. This antibody is Biotin conjugated. Tested in the following application: ELISA
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