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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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Changes in the PWL by Hyperoside. (A) PWL in the CFA-treated paws (ipsilateral) from the control, Hyp, CFA + saline, and CFA + Hyp treated mice. (B) PWL in the right hind paws (contralateral) from the control, Hyp, CFA + saline, and CFA + Hyp treated mice. Values (in A and B) were significantly different from saline control * p < 0.05, ** p < 0.01; from CFA-injected alone, # p < 0.05. (C) Paw volume in the CFA-treated and contralateral paws from control and Hyp treated mice. Values (in C) were significantly different from contralateral paws ** p < 0.01.
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Figure 6: Changes in the PWL by Hyperoside. (A) PWL in the CFA-treated paws (ipsilateral) from the control, Hyp, CFA + saline, and CFA + Hyp treated mice. (B) PWL in the right hind paws (contralateral) from the control, Hyp, CFA + saline, and CFA + Hyp treated mice. Values (in A and B) were significantly different from saline control * p < 0.05, ** p < 0.01; from CFA-injected alone, # p < 0.05. (C) Paw volume in the CFA-treated and contralateral paws from control and Hyp treated mice. Values (in C) were significantly different from contralateral paws ** p < 0.01.

Mentions: As illustrated in Fig. 1 and Fig. 2, administration of Hyp reversed up-regulation of NR2B receptors in the PAG of CFA-injected rats, it is reasonable to predict Hyp inhibiting the thermal hyperalgesia induced by chronic inflammation. As shown in Fig. 6, administration of Hyp (100 mg/kg, i.g. twice daily for 3 days) alone did not change PWL in hindpaw saline-injected rats. However, Hyp could significantly reverse ipsilateral PWL (from 7.2 ± 0.9 s to 11.8 ± 1.3 s; n = 8, p < 0.05 vs CFA-injected alone; Fig. 6B) and contralateral PWL (from 10.2 ± 0.6 to 12.1 ± 0.7 s; n = 8, p < 0.05 vs CFA-injected alone; Fig. 6B) in CFA-injected rats.


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)

Changes in the PWL by Hyperoside. (A) PWL in the CFA-treated paws (ipsilateral) from the control, Hyp, CFA + saline, and CFA + Hyp treated mice. (B) PWL in the right hind paws (contralateral) from the control, Hyp, CFA + saline, and CFA + Hyp treated mice. Values (in A and B) were significantly different from saline control * p < 0.05, ** p < 0.01; from CFA-injected alone, # p < 0.05. (C) Paw volume in the CFA-treated and contralateral paws from control and Hyp treated mice. Values (in C) were significantly different from contralateral paws ** p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Changes in the PWL by Hyperoside. (A) PWL in the CFA-treated paws (ipsilateral) from the control, Hyp, CFA + saline, and CFA + Hyp treated mice. (B) PWL in the right hind paws (contralateral) from the control, Hyp, CFA + saline, and CFA + Hyp treated mice. Values (in A and B) were significantly different from saline control * p < 0.05, ** p < 0.01; from CFA-injected alone, # p < 0.05. (C) Paw volume in the CFA-treated and contralateral paws from control and Hyp treated mice. Values (in C) were significantly different from contralateral paws ** p < 0.01.
Mentions: As illustrated in Fig. 1 and Fig. 2, administration of Hyp reversed up-regulation of NR2B receptors in the PAG of CFA-injected rats, it is reasonable to predict Hyp inhibiting the thermal hyperalgesia induced by chronic inflammation. As shown in Fig. 6, administration of Hyp (100 mg/kg, i.g. twice daily for 3 days) alone did not change PWL in hindpaw saline-injected rats. However, Hyp could significantly reverse ipsilateral PWL (from 7.2 ± 0.9 s to 11.8 ± 1.3 s; n = 8, p < 0.05 vs CFA-injected alone; Fig. 6B) and contralateral PWL (from 10.2 ± 0.6 to 12.1 ± 0.7 s; n = 8, p < 0.05 vs CFA-injected alone; Fig. 6B) in CFA-injected rats.

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