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Direct application of the TNF-alpha inhibitor, etanercept, does not affect CGRP expression and phenotypic change of DRG neurons following application of nucleus pulposus onto injured sciatic nerves in rats.
Spine (Phila Pa 1976). 2008 Oct 15; 33(22):2403-8.S

Abstract

STUDY DESIGN

Immunohistological and behavioral analysis of the effect of a tumor necrosis factor alpha (TNF-alpha) inhibitor in an injured-nerve model.

OBJECTIVE

To examine the effect of direct application of a TNF-alpha inhibitor (etanercept) on injured-nerve pain caused by nucleus pulposus.

SUMMARY AND BACKGROUND DATA

TNF-alpha is thought to play a crucial role in radicular pain. Calcitonin gene-related peptide (CGRP) is an inflammatory neuropeptide found in small sensory neurons. We have reported that CGRP appears in medium and large dorsal root ganglion (DRG) neurons that transmit proprioception in physiologic conditions. The purpose of the current study was to examine the change in behavior and phenotypic change of CGRP-immunoreactive DRG neurons by the TNF-alpha inhibitor, etanercept, in a disc herniation model.

METHODS

For the injured-nerve model, nucleus pulposus was applied to the sciatic nerve and the sciatic nerve pinched. Saline (10 microL; n = 10), as a control, or etanercept (150 microg: n = 10) were applied to sciatic nerves simultaneously. Mechanical allodynia was examined. Immunohistochemistry was used to examine CGRP expression in L5 DRGs.

RESULTS

Significant mechanical allodynia for 10 days was seen in the injured-nerve group compared with sham-operated animals. Etanercept ameliorated the mechanical allodynia slightly on day 2; however, there was no effect on other days. CGRP immunoreactivity was upregulated in the L5 DRG neurons of injured-nerve groups compared with the sham-operated group (P < 0.01). However, etanercept did not affect CGRP expression after nerve injury (P > 0.05). Proportions of CGRP- immunoreactive medium and large neurons were not significantly different in the nerve injury + saline group compared with the injury + etanercept group (P > 0.05).

CONCLUSION

Our results indicate that direct application of a TNF-alpha inhibitor had a small effect on acute pain behavior and may not be effective for suppression of inflammatory peptides in the current disc-herniation model.

Authors+Show Affiliations

Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.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 availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18824950

Citation

Norimoto, Masaki, et al. "Direct Application of the TNF-alpha Inhibitor, Etanercept, Does Not Affect CGRP Expression and Phenotypic Change of DRG Neurons Following Application of Nucleus Pulposus Onto Injured Sciatic Nerves in Rats." Spine, vol. 33, no. 22, 2008, pp. 2403-8.
Norimoto M, Ohtori S, Yamashita M, et al. Direct application of the TNF-alpha inhibitor, etanercept, does not affect CGRP expression and phenotypic change of DRG neurons following application of nucleus pulposus onto injured sciatic nerves in rats. Spine (Phila Pa 1976). 2008;33(22):2403-8.
Norimoto, M., Ohtori, S., Yamashita, M., Inoue, G., Yamauchi, K., Koshi, T., Suzuki, M., Orita, S., Eguchi, Y., Sugiura, A., Ochiai, N., Takaso, M., & Takahashi, K. (2008). Direct application of the TNF-alpha inhibitor, etanercept, does not affect CGRP expression and phenotypic change of DRG neurons following application of nucleus pulposus onto injured sciatic nerves in rats. Spine, 33(22), 2403-8. https://doi.org/10.1097/BRS.0b013e31818441a2
Norimoto M, et al. Direct Application of the TNF-alpha Inhibitor, Etanercept, Does Not Affect CGRP Expression and Phenotypic Change of DRG Neurons Following Application of Nucleus Pulposus Onto Injured Sciatic Nerves in Rats. Spine (Phila Pa 1976). 2008 Oct 15;33(22):2403-8. PubMed PMID: 18824950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct application of the TNF-alpha inhibitor, etanercept, does not affect CGRP expression and phenotypic change of DRG neurons following application of nucleus pulposus onto injured sciatic nerves in rats. AU - Norimoto,Masaki, AU - Ohtori,Seiji, AU - Yamashita,Masaomi, AU - Inoue,Gen, AU - Yamauchi,Kazuyo, AU - Koshi,Takana, AU - Suzuki,Munetaka, AU - Orita,Sumihisa, AU - Eguchi,Yawara, AU - Sugiura,Ai, AU - Ochiai,Nobuyasu, AU - Takaso,Masashi, AU - Takahashi,Kazuhisa, PY - 2008/10/1/pubmed PY - 2008/12/17/medline PY - 2008/10/1/entrez SP - 2403 EP - 8 JF - Spine JO - Spine (Phila Pa 1976) VL - 33 IS - 22 N2 - STUDY DESIGN: Immunohistological and behavioral analysis of the effect of a tumor necrosis factor alpha (TNF-alpha) inhibitor in an injured-nerve model. OBJECTIVE: To examine the effect of direct application of a TNF-alpha inhibitor (etanercept) on injured-nerve pain caused by nucleus pulposus. SUMMARY AND BACKGROUND DATA: TNF-alpha is thought to play a crucial role in radicular pain. Calcitonin gene-related peptide (CGRP) is an inflammatory neuropeptide found in small sensory neurons. We have reported that CGRP appears in medium and large dorsal root ganglion (DRG) neurons that transmit proprioception in physiologic conditions. The purpose of the current study was to examine the change in behavior and phenotypic change of CGRP-immunoreactive DRG neurons by the TNF-alpha inhibitor, etanercept, in a disc herniation model. METHODS: For the injured-nerve model, nucleus pulposus was applied to the sciatic nerve and the sciatic nerve pinched. Saline (10 microL; n = 10), as a control, or etanercept (150 microg: n = 10) were applied to sciatic nerves simultaneously. Mechanical allodynia was examined. Immunohistochemistry was used to examine CGRP expression in L5 DRGs. RESULTS: Significant mechanical allodynia for 10 days was seen in the injured-nerve group compared with sham-operated animals. Etanercept ameliorated the mechanical allodynia slightly on day 2; however, there was no effect on other days. CGRP immunoreactivity was upregulated in the L5 DRG neurons of injured-nerve groups compared with the sham-operated group (P < 0.01). However, etanercept did not affect CGRP expression after nerve injury (P > 0.05). Proportions of CGRP- immunoreactive medium and large neurons were not significantly different in the nerve injury + saline group compared with the injury + etanercept group (P > 0.05). CONCLUSION: Our results indicate that direct application of a TNF-alpha inhibitor had a small effect on acute pain behavior and may not be effective for suppression of inflammatory peptides in the current disc-herniation model. SN - 1528-1159 UR - https://www.unboundmedicine.com/medline/citation/18824950/Direct_application_of_the_TNF_alpha_inhibitor_etanercept_does_not_affect_CGRP_expression_and_phenotypic_change_of_DRG_neurons_following_application_of_nucleus_pulposus_onto_injured_sciatic_nerves_in_rats_ L2 - https://doi.org/10.1097/BRS.0b013e31818441a2 DB - PRIME DP - Unbound Medicine ER -