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Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain.
Exp Neurol. 2009 Feb; 215(2):298-307.EN

Abstract

Activation of N-methyl-d-aspartate (NMDA) receptors in the spinal dorsal horn has been shown to be essential for the initiation of central sensitization and the hyperexcitability of dorsal horn neurons in chronic pain. However, whether the spinal NR2B-containing NMDA (NMDA-2B) receptors are involved still remains largely unclear. Using behavioral test and in vivo extracellular electrophysiological recording in L5 spinal nerve-ligated (SNL) neuropathic rats, we investigate the roles of spinal cord NMDA-2B receptors in the development of neuropathic pain. Our study showed that intrathecal (i.t.) injection of Ro 25-6981, a selective NMDA-2B receptor antagonist, had a dose-dependent anti-allodynic effect without causing motor dysfunction. Furthermore, i.t. application of another NMDA-2B receptor antagonist ifenprodil prior to SNL also significantly inhibited the mechanical allodynia but not the thermal hyperalgesia. These data suggest that NMDA-2B receptors at the spinal cord level play an important role in the development of neuropathic pain, especially at the early stage following nerve injury. In addition, spinal administration of Ro 25-6981 not only had a dose-dependent inhibitory effect on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons in both normal and SNL rats, but also significantly inhibited the long-term potentiation (LTP) in the C-fiber responses of WDR neurons induced by high-frequency stimulation (HFS) applied to the sciatic nerve. These results indicate that activation of the dorsal horn NMDA-2B receptors may be crucial for the spinal nociceptive synaptic transmission and for the development of long-lasting spinal hyperexcitability following nerve injury. In conclusion, the spinal cord NMDA-2B receptors play a role in the development of central sensitization and neuropathic pain via the induction of LTP in dorsal horn nociceptive synaptic transmission. Therefore, the spinal cord NMDA-2B receptor is likely to be a target for clinical pain therapy.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Qu XX
Neuroscience Research Institute and Department of Neurobiology, Peking University, 38 Xue-Yuan Road, Beijing 100191, PR China.
Cai J
No affiliation info available
Li MJ
No affiliation info available
Chi YN
No affiliation info available
Liao FF
No affiliation info available
Liu FY
No affiliation info available
Wan Y
No affiliation info available
Han JS
No affiliation info available
Xing GG
No affiliation info available

MeSH

Action PotentialsAnalysis of VarianceAnimalsDisease Models, AnimalDose-Response Relationship, DrugElectric StimulationExcitatory Amino Acid AntagonistsHyperalgesiaLong-Term PotentiationMaleMotor ActivityNerve FibersNeuralgiaPain MeasurementPain ThresholdPhenolsPiperidinesRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSensory Receptor CellsSpinal CordTime Factors

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19046970

Citation

Qu, Xiao-Xiu, et al. "Role of the Spinal Cord NR2B-containing NMDA Receptors in the Development of Neuropathic Pain." Experimental Neurology, vol. 215, no. 2, 2009, pp. 298-307.
Qu XX, Cai J, Li MJ, et al. Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain. Exp Neurol. 2009;215(2):298-307.
Qu, X. X., Cai, J., Li, M. J., Chi, Y. N., Liao, F. F., Liu, F. Y., Wan, Y., Han, J. S., & Xing, G. G. (2009). Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain. Experimental Neurology, 215(2), 298-307. https://doi.org/10.1016/j.expneurol.2008.10.018
Qu XX, et al. Role of the Spinal Cord NR2B-containing NMDA Receptors in the Development of Neuropathic Pain. Exp Neurol. 2009;215(2):298-307. PubMed PMID: 19046970.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain. AU - Qu,Xiao-Xiu, AU - Cai,Jie, AU - Li,Ming-Jia, AU - Chi,Ye-Nan, AU - Liao,Fei-Fei, AU - Liu,Feng-Yu, AU - Wan,You, AU - Han,Ji-Sheng, AU - Xing,Guo-Gang, Y1 - 2008/11/12/ PY - 2008/08/26/received PY - 2008/10/22/revised PY - 2008/10/24/accepted PY - 2008/12/3/pubmed PY - 2009/4/9/medline PY - 2008/12/3/entrez SP - 298 EP - 307 JF - Experimental neurology JO - Exp Neurol VL - 215 IS - 2 N2 - Activation of N-methyl-d-aspartate (NMDA) receptors in the spinal dorsal horn has been shown to be essential for the initiation of central sensitization and the hyperexcitability of dorsal horn neurons in chronic pain. However, whether the spinal NR2B-containing NMDA (NMDA-2B) receptors are involved still remains largely unclear. Using behavioral test and in vivo extracellular electrophysiological recording in L5 spinal nerve-ligated (SNL) neuropathic rats, we investigate the roles of spinal cord NMDA-2B receptors in the development of neuropathic pain. Our study showed that intrathecal (i.t.) injection of Ro 25-6981, a selective NMDA-2B receptor antagonist, had a dose-dependent anti-allodynic effect without causing motor dysfunction. Furthermore, i.t. application of another NMDA-2B receptor antagonist ifenprodil prior to SNL also significantly inhibited the mechanical allodynia but not the thermal hyperalgesia. These data suggest that NMDA-2B receptors at the spinal cord level play an important role in the development of neuropathic pain, especially at the early stage following nerve injury. In addition, spinal administration of Ro 25-6981 not only had a dose-dependent inhibitory effect on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons in both normal and SNL rats, but also significantly inhibited the long-term potentiation (LTP) in the C-fiber responses of WDR neurons induced by high-frequency stimulation (HFS) applied to the sciatic nerve. These results indicate that activation of the dorsal horn NMDA-2B receptors may be crucial for the spinal nociceptive synaptic transmission and for the development of long-lasting spinal hyperexcitability following nerve injury. In conclusion, the spinal cord NMDA-2B receptors play a role in the development of central sensitization and neuropathic pain via the induction of LTP in dorsal horn nociceptive synaptic transmission. Therefore, the spinal cord NMDA-2B receptor is likely to be a target for clinical pain therapy. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/19046970/Role_of_the_spinal_cord_NR2B_containing_NMDA_receptors_in_the_development_of_neuropathic_pain_ DB - PRIME DP - Unbound Medicine ER -