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Intrathecal injection of the sigma(1) receptor antagonist BD1047 blocks both mechanical allodynia and increases in spinal NR1 expression during the induction phase of rodent neuropathic pain.
Anesthesiology. 2008 Nov; 109(5):879-89.A

Abstract

BACKGROUND

Selective blockade of spinal sigma(1) receptors (Sig-1R) suppresses nociceptive behaviors in the mouse formalin test. The current study was designed to verify whether intrathecal Sig-1R antagonists can also suppress chronic neuropathic pain.

METHODS

Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. The Sig-1R antagonist BD1047 was administered intrathecally twice daily from postoperative days 0 to 5 (induction phase of neuropathic pain) or from days 15 to 20 (maintenance phase). Western blot and immunohistochemistry were performed to determine changes in Sig-1R expression and to examine the effect of BD1047 on N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation in spinal cord dorsal horn from neuropathic rats.

RESULTS

BD1047 administered on postoperative days 0-5 significantly attenuated CCI-induced mechanical allodynia, but not thermal hyperalgesia, and this suppression was blocked by intrathecal administration of the Sig-1R agonist PRE084. In contrast, BD1047 treatment during the maintenance phase of neuropathic pain had no effect on mechanical allodynia. Sig-1R expression significantly increased in the ipsilateral spinal cord dorsal horn from days 1 to 3 after CCI. Importantly, BD1047 (30 nmol) administered intrathecally during the induction, but not the maintenance phase, blocked the CCI-induced increase in N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation.

CONCLUSIONS

These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain.

Authors+Show Affiliations

College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, Republic of Korea.No affiliation info availableNo affiliation info availableNo 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

18946301

Citation

Roh, Dae-Hyun, et al. "Intrathecal Injection of the Sigma(1) Receptor Antagonist BD1047 Blocks Both Mechanical Allodynia and Increases in Spinal NR1 Expression During the Induction Phase of Rodent Neuropathic Pain." Anesthesiology, vol. 109, no. 5, 2008, pp. 879-89.
Roh DH, Kim HW, Yoon SY, et al. Intrathecal injection of the sigma(1) receptor antagonist BD1047 blocks both mechanical allodynia and increases in spinal NR1 expression during the induction phase of rodent neuropathic pain. Anesthesiology. 2008;109(5):879-89.
Roh, D. H., Kim, H. W., Yoon, S. Y., Seo, H. S., Kwon, Y. B., Kim, K. W., Han, H. J., Beitz, A. J., Na, H. S., & Lee, J. H. (2008). Intrathecal injection of the sigma(1) receptor antagonist BD1047 blocks both mechanical allodynia and increases in spinal NR1 expression during the induction phase of rodent neuropathic pain. Anesthesiology, 109(5), 879-89. https://doi.org/10.1097/ALN.0b013e3181895a83
Roh DH, et al. Intrathecal Injection of the Sigma(1) Receptor Antagonist BD1047 Blocks Both Mechanical Allodynia and Increases in Spinal NR1 Expression During the Induction Phase of Rodent Neuropathic Pain. Anesthesiology. 2008;109(5):879-89. PubMed PMID: 18946301.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrathecal injection of the sigma(1) receptor antagonist BD1047 blocks both mechanical allodynia and increases in spinal NR1 expression during the induction phase of rodent neuropathic pain. AU - Roh,Dae-Hyun, AU - Kim,Hyun-Woo, AU - Yoon,Seo-Yeon, AU - Seo,Hyoung-Sig, AU - Kwon,Young-Bae, AU - Kim,Kee-Won, AU - Han,Ho-Jae, AU - Beitz,Alvin J, AU - Na,Heung-Sik, AU - Lee,Jang-Hern, PY - 2008/10/24/pubmed PY - 2008/11/19/medline PY - 2008/10/24/entrez SP - 879 EP - 89 JF - Anesthesiology JO - Anesthesiology VL - 109 IS - 5 N2 - BACKGROUND: Selective blockade of spinal sigma(1) receptors (Sig-1R) suppresses nociceptive behaviors in the mouse formalin test. The current study was designed to verify whether intrathecal Sig-1R antagonists can also suppress chronic neuropathic pain. METHODS: Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. The Sig-1R antagonist BD1047 was administered intrathecally twice daily from postoperative days 0 to 5 (induction phase of neuropathic pain) or from days 15 to 20 (maintenance phase). Western blot and immunohistochemistry were performed to determine changes in Sig-1R expression and to examine the effect of BD1047 on N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation in spinal cord dorsal horn from neuropathic rats. RESULTS: BD1047 administered on postoperative days 0-5 significantly attenuated CCI-induced mechanical allodynia, but not thermal hyperalgesia, and this suppression was blocked by intrathecal administration of the Sig-1R agonist PRE084. In contrast, BD1047 treatment during the maintenance phase of neuropathic pain had no effect on mechanical allodynia. Sig-1R expression significantly increased in the ipsilateral spinal cord dorsal horn from days 1 to 3 after CCI. Importantly, BD1047 (30 nmol) administered intrathecally during the induction, but not the maintenance phase, blocked the CCI-induced increase in N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation. CONCLUSIONS: These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain. SN - 1528-1175 UR - https://www.unboundmedicine.com/medline/citation/18946301/Intrathecal_injection_of_the_sigma_1__receptor_antagonist_BD1047_blocks_both_mechanical_allodynia_and_increases_in_spinal_NR1_expression_during_the_induction_phase_of_rodent_neuropathic_pain_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/ALN.0b013e3181895a83 DB - PRIME DP - Unbound Medicine ER -