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Depletion of capsaicin-sensitive afferents prevents lamina-dependent increases in spinal N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation associated with thermal hyperalgesia in neuropathic rats.
Eur J Pain. 2008 Jul; 12(5):552-63.EJ

Abstract

Phosphorylation of the N-methyl-D-aspartate (NMDA) receptor NR1 subunit (pNR1) in the spinal cord is associated with increased neuronal responsiveness, which underlies the process of central sensitization. Because of the importance of NR1 in central sensitization, the first goal of this study was to examine both time- and lamina-dependent changes in spinal NR1 and pNR1 expression in a chronic constriction injury (CCI) model of neuropathic pain. Increased excitability of capsaicin sensitive primary afferents (CSPAs), which express TRPV1 receptors, also contributes to central sensitization. Thus, we next examined whether the depletion of CSPAs with resiniferatoxin (RTX) modified the change of spinal NR1 and pNR1 expression induced by CCI. Experimental rats were euthanized at 1, 3, 7, 14, and 28 days post-CCI surgery and spinal cords processed for NR1 or pNR1 immunostaining. The number of NR1 or pNR1-immunoreactive neurons was significantly increased in all lamina (I-VI) of the ipsilateral L4/L5 dorsal horn from 1 or 7 days post-CCI, respectively. Pretreatment with RTX (0.3mg/kg, s.c. in the scruff of the neck or intraplantar) 2 days prior to CCI completely prevented induction of thermal hyperalgesia, but not mechanical allodynia in neuropathic rats. Interestingly, RTX treatment significantly attenuated the CCI-induced upregulation of NR1 and pNR1 in spinal laminae I-II and V-VI, but not laminae III-IV as compared with that of vehicle-treated CCI rats. These findings demonstrate that the increased expression of NR1 and pNR1 in spinal laminae I-II and V-VI is dependent on activation of CSPAs, which ultimately contribute to the development of thermal hyperalgesia in neuropathic rats.

Authors+Show Affiliations

Department of Veterinary Physiology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17933570

Citation

Roh, Dae-Hyun, et al. "Depletion of Capsaicin-sensitive Afferents Prevents Lamina-dependent Increases in Spinal N-methyl-D-aspartate Receptor Subunit 1 Expression and Phosphorylation Associated With Thermal Hyperalgesia in Neuropathic Rats." European Journal of Pain (London, England), vol. 12, no. 5, 2008, pp. 552-63.
Roh DH, Kim HW, Yoon SY, et al. Depletion of capsaicin-sensitive afferents prevents lamina-dependent increases in spinal N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation associated with thermal hyperalgesia in neuropathic rats. Eur J Pain. 2008;12(5):552-63.
Roh, D. H., Kim, H. W., Yoon, S. Y., Seo, H. S., Kwon, Y. B., Han, H. J., Beitz, A. J., & Lee, J. H. (2008). Depletion of capsaicin-sensitive afferents prevents lamina-dependent increases in spinal N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation associated with thermal hyperalgesia in neuropathic rats. European Journal of Pain (London, England), 12(5), 552-63.
Roh DH, et al. Depletion of Capsaicin-sensitive Afferents Prevents Lamina-dependent Increases in Spinal N-methyl-D-aspartate Receptor Subunit 1 Expression and Phosphorylation Associated With Thermal Hyperalgesia in Neuropathic Rats. Eur J Pain. 2008;12(5):552-63. PubMed PMID: 17933570.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Depletion of capsaicin-sensitive afferents prevents lamina-dependent increases in spinal N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation associated with thermal hyperalgesia in neuropathic rats. AU - Roh,Dae-Hyun, AU - Kim,Hyun-Woo, AU - Yoon,Seo-Yeon, AU - Seo,Hyoung-Sig, AU - Kwon,Young-Bae, AU - Han,Ho-Jae, AU - Beitz,Alvin J, AU - Lee,Jang-Hern, Y1 - 2007/10/22/ PY - 2007/04/15/received PY - 2007/08/17/revised PY - 2007/09/03/accepted PY - 2007/10/16/pubmed PY - 2008/9/27/medline PY - 2007/10/16/entrez SP - 552 EP - 63 JF - European journal of pain (London, England) JO - Eur J Pain VL - 12 IS - 5 N2 - Phosphorylation of the N-methyl-D-aspartate (NMDA) receptor NR1 subunit (pNR1) in the spinal cord is associated with increased neuronal responsiveness, which underlies the process of central sensitization. Because of the importance of NR1 in central sensitization, the first goal of this study was to examine both time- and lamina-dependent changes in spinal NR1 and pNR1 expression in a chronic constriction injury (CCI) model of neuropathic pain. Increased excitability of capsaicin sensitive primary afferents (CSPAs), which express TRPV1 receptors, also contributes to central sensitization. Thus, we next examined whether the depletion of CSPAs with resiniferatoxin (RTX) modified the change of spinal NR1 and pNR1 expression induced by CCI. Experimental rats were euthanized at 1, 3, 7, 14, and 28 days post-CCI surgery and spinal cords processed for NR1 or pNR1 immunostaining. The number of NR1 or pNR1-immunoreactive neurons was significantly increased in all lamina (I-VI) of the ipsilateral L4/L5 dorsal horn from 1 or 7 days post-CCI, respectively. Pretreatment with RTX (0.3mg/kg, s.c. in the scruff of the neck or intraplantar) 2 days prior to CCI completely prevented induction of thermal hyperalgesia, but not mechanical allodynia in neuropathic rats. Interestingly, RTX treatment significantly attenuated the CCI-induced upregulation of NR1 and pNR1 in spinal laminae I-II and V-VI, but not laminae III-IV as compared with that of vehicle-treated CCI rats. These findings demonstrate that the increased expression of NR1 and pNR1 in spinal laminae I-II and V-VI is dependent on activation of CSPAs, which ultimately contribute to the development of thermal hyperalgesia in neuropathic rats. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/17933570/Depletion_of_capsaicin_sensitive_afferents_prevents_lamina_dependent_increases_in_spinal_N_methyl_D_aspartate_receptor_subunit_1_expression_and_phosphorylation_associated_with_thermal_hyperalgesia_in_neuropathic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1090-3801(07)00650-7 DB - PRIME DP - Unbound Medicine ER -