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Effect of etanercept, a tumor necrosis factor-alpha inhibitor, on neuropathic pain in the rat chronic constriction injury model.
Spine (Phila Pa 1976). 2008 Feb 01; 33(3):227-34.S

Abstract

STUDY DESIGN

The effects of a low, local dose of a tumor necrosis factor-alpha (TNF-alpha) inhibitor on neuropathic pain behaviors in a rat chronic constriction injury model were evaluated.

OBJECTIVE

To investigate whether a peripherally implanted polymer drug depot can deliver a dose of etanercept sufficient to reduce thermal hyperalgesia and mechanical allodynia in a rat model of neuropathic pain.

SUMMARY OF BACKGROUND DATA

TNF-alpha inhibitors reduce pain-associated behavior in experimental models of neuropathic pain. Moreover, systemic injections of TNF-alpha inhibitors have suggested some efficacy in treating sciatic pain in limited, off-label clinical studies. Improvements in these results may be obtained by optimal dosing via targeted, sustained delivery at the site of disc-induced inflammation.

METHODS

Unilateral chronic constriction injury was applied to the sciatic nerve of 56 male, Wistar rats. Four groups of animals (n = 7) received 0.5 mL phosphate-buffered saline every 3 days, 0.3 or 3 mg/kg etanercept every 3 days, or gabapentin (60 mg/kg) 1 hour before each behavioral test all via subcutaneous injection. Two groups of animals received 1.5 or 3.0 microg/h etanercept delivered by poly(lactic-co-glycolic acid) (PLGA) millicylinders (1 mm diameter x 10 mm long) implanted near the injured sciatic nerve. One group received a PLGA millicylinder implanted near the injured sciatic nerve. The final group received 3.0 microg/h etanercept via PLGA millicylinder implanted next to the uninjured, contralateral sciatic nerve.

RESULTS

A low, local dose of etanercept (approximately 3 microg/h) delivered by a polymer depot significantly reduced (P < 0.05) thermal hyperalgesia for 57 days as compared to polymer depot without drug or an etanercept-loaded depot implanted near the contralateral sciatic nerve, and equivalent to a 10-fold higher dose delivered by repeat subcutaneous injection.

CONCLUSION

This preclinical study indicates that delivering TNF-alpha inhibitors by means of a locally administered polymeric formulation provides long-lasting analgesia in an inflammatory neuropathic pain model.

Authors+Show Affiliations

Medtronic, Spinal and Biologics, Memphis, TN 38132, USA. john.zanella@medtronic.comNo 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

18303453

Citation

Zanella, John M., et al. "Effect of Etanercept, a Tumor Necrosis Factor-alpha Inhibitor, On Neuropathic Pain in the Rat Chronic Constriction Injury Model." Spine, vol. 33, no. 3, 2008, pp. 227-34.
Zanella JM, Burright EN, Hildebrand K, et al. Effect of etanercept, a tumor necrosis factor-alpha inhibitor, on neuropathic pain in the rat chronic constriction injury model. Spine (Phila Pa 1976). 2008;33(3):227-34.
Zanella, J. M., Burright, E. N., Hildebrand, K., Hobot, C., Cox, M., Christoferson, L., & McKay, W. F. (2008). Effect of etanercept, a tumor necrosis factor-alpha inhibitor, on neuropathic pain in the rat chronic constriction injury model. Spine, 33(3), 227-34. https://doi.org/10.1097/BRS.0b013e318162340a
Zanella JM, et al. Effect of Etanercept, a Tumor Necrosis Factor-alpha Inhibitor, On Neuropathic Pain in the Rat Chronic Constriction Injury Model. Spine (Phila Pa 1976). 2008 Feb 1;33(3):227-34. PubMed PMID: 18303453.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of etanercept, a tumor necrosis factor-alpha inhibitor, on neuropathic pain in the rat chronic constriction injury model. AU - Zanella,John M, AU - Burright,Eric N, AU - Hildebrand,Keith, AU - Hobot,Chris, AU - Cox,Mark, AU - Christoferson,Laura, AU - McKay,William F, PY - 2008/2/28/pubmed PY - 2008/3/28/medline PY - 2008/2/28/entrez SP - 227 EP - 34 JF - Spine JO - Spine (Phila Pa 1976) VL - 33 IS - 3 N2 - STUDY DESIGN: The effects of a low, local dose of a tumor necrosis factor-alpha (TNF-alpha) inhibitor on neuropathic pain behaviors in a rat chronic constriction injury model were evaluated. OBJECTIVE: To investigate whether a peripherally implanted polymer drug depot can deliver a dose of etanercept sufficient to reduce thermal hyperalgesia and mechanical allodynia in a rat model of neuropathic pain. SUMMARY OF BACKGROUND DATA: TNF-alpha inhibitors reduce pain-associated behavior in experimental models of neuropathic pain. Moreover, systemic injections of TNF-alpha inhibitors have suggested some efficacy in treating sciatic pain in limited, off-label clinical studies. Improvements in these results may be obtained by optimal dosing via targeted, sustained delivery at the site of disc-induced inflammation. METHODS: Unilateral chronic constriction injury was applied to the sciatic nerve of 56 male, Wistar rats. Four groups of animals (n = 7) received 0.5 mL phosphate-buffered saline every 3 days, 0.3 or 3 mg/kg etanercept every 3 days, or gabapentin (60 mg/kg) 1 hour before each behavioral test all via subcutaneous injection. Two groups of animals received 1.5 or 3.0 microg/h etanercept delivered by poly(lactic-co-glycolic acid) (PLGA) millicylinders (1 mm diameter x 10 mm long) implanted near the injured sciatic nerve. One group received a PLGA millicylinder implanted near the injured sciatic nerve. The final group received 3.0 microg/h etanercept via PLGA millicylinder implanted next to the uninjured, contralateral sciatic nerve. RESULTS: A low, local dose of etanercept (approximately 3 microg/h) delivered by a polymer depot significantly reduced (P < 0.05) thermal hyperalgesia for 57 days as compared to polymer depot without drug or an etanercept-loaded depot implanted near the contralateral sciatic nerve, and equivalent to a 10-fold higher dose delivered by repeat subcutaneous injection. CONCLUSION: This preclinical study indicates that delivering TNF-alpha inhibitors by means of a locally administered polymeric formulation provides long-lasting analgesia in an inflammatory neuropathic pain model. SN - 1528-1159 UR - https://www.unboundmedicine.com/medline/citation/18303453/Effect_of_etanercept_a_tumor_necrosis_factor_alpha_inhibitor_on_neuropathic_pain_in_the_rat_chronic_constriction_injury_model_ L2 - https://doi.org/10.1097/BRS.0b013e318162340a DB - PRIME DP - Unbound Medicine ER -