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A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain.

Hu J, Wang Z, Guo YY, Zhang XN, Xu ZH, Liu SB, Guo HJ, Yang Q, Zhang FX, Sun XL, Zhao MG - Mol Pain (2009)

Bottom Line: Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA) caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered.PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats.Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. hujing2@fmmu.edu.cn

ABSTRACT
The midbrain periaqueductal grey (PAG) is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA) caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp), one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

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Immunostaining of NMDA receptors in PAG. Immunostaining was performed in the coronal midbrain slices containing the PAG. (A) Expression of NR2A in saline control, CFA, and CFA + Hyp treated mice. (B) Expression of NR2B in saline control, CFA, and CFA + Hyp treated mice. Scalebar (in B): A, B, 500 μM. DMPAG: Dorsomed periaqueductal gray; LPAG: Lateral periaqueductal gray.
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Figure 2: Immunostaining of NMDA receptors in PAG. Immunostaining was performed in the coronal midbrain slices containing the PAG. (A) Expression of NR2A in saline control, CFA, and CFA + Hyp treated mice. (B) Expression of NR2B in saline control, CFA, and CFA + Hyp treated mice. Scalebar (in B): A, B, 500 μM. DMPAG: Dorsomed periaqueductal gray; LPAG: Lateral periaqueductal gray.

Mentions: To further confirm the selective changes of NMDA receptor subunits in PAG after CFA-injection, we performed immunostaining in the midbrain sections containing the PAG in mice. As shown in Fig. 2, expression of NR2B subunit was significantly increased in the LPAG of CFA-injected mice (n = 5) as compared with control mice (n = 6). Contrary to the NR2B, NR2A subunit was not significantly changed (n = 5). Administration of Hyp (100 mg/kg, i.g. twice daily for 3 days) reversed up-regulation of NR2B subunit in the LPAG of CFA-injected mice.


A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain.

Hu J, Wang Z, Guo YY, Zhang XN, Xu ZH, Liu SB, Guo HJ, Yang Q, Zhang FX, Sun XL, Zhao MG - Mol Pain (2009)

Immunostaining of NMDA receptors in PAG. Immunostaining was performed in the coronal midbrain slices containing the PAG. (A) Expression of NR2A in saline control, CFA, and CFA + Hyp treated mice. (B) Expression of NR2B in saline control, CFA, and CFA + Hyp treated mice. Scalebar (in B): A, B, 500 μM. DMPAG: Dorsomed periaqueductal gray; LPAG: Lateral periaqueductal gray.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803476&req=5

Figure 2: Immunostaining of NMDA receptors in PAG. Immunostaining was performed in the coronal midbrain slices containing the PAG. (A) Expression of NR2A in saline control, CFA, and CFA + Hyp treated mice. (B) Expression of NR2B in saline control, CFA, and CFA + Hyp treated mice. Scalebar (in B): A, B, 500 μM. DMPAG: Dorsomed periaqueductal gray; LPAG: Lateral periaqueductal gray.
Mentions: To further confirm the selective changes of NMDA receptor subunits in PAG after CFA-injection, we performed immunostaining in the midbrain sections containing the PAG in mice. As shown in Fig. 2, expression of NR2B subunit was significantly increased in the LPAG of CFA-injected mice (n = 5) as compared with control mice (n = 6). Contrary to the NR2B, NR2A subunit was not significantly changed (n = 5). Administration of Hyp (100 mg/kg, i.g. twice daily for 3 days) reversed up-regulation of NR2B subunit in the LPAG of CFA-injected mice.

Bottom Line: Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA) caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered.PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats.Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. hujing2@fmmu.edu.cn

ABSTRACT
The midbrain periaqueductal grey (PAG) is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA) caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp), one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

Show MeSH
Related in: MedlinePlus