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Systemic and spinal administration of etanercept, a tumor necrosis factor alpha inhibitor, blocks tactile allodynia in diabetic mice.
Acta Diabetol. 2011 Jun; 48(2):135-42.AD

Abstract

Painful diabetic neuropathy is one of the most common forms of neuropathic pain syndromes. Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated as a key pain mediator in the development and maintenance of neuropathic pain conditions. Recent studies showed that endogenous TNF-alpha production was also accelerated in neural tissues and spinal cord under chronic hyperglycemia. Thus, in this study, we investigated whether pharmacological inhibition of TNF-alpha by etanercept, a TNF-alpha antagonist, could block behavioral sign of diabetic neuropathic pain. Diabetes was induced by streptozotocin (STZ) (200 mg/kg, i.p.) in Balb-c mice and behavioral tests were performed between 45 and 60 days after STZ administration. Mechanical and thermal sensitivities were measured by a series of calibrated Von Frey filaments and hot plate test, respectively. Etanercept was given by either intravenous (i.v.), intrathecal (i.th.) or intraplantar (i.pl.) routes to the diabetic mice. Tactile allodynia, but not thermal hyperalgesia, developed in diabetic mice. Both i.v. (1, 10 and 20 mg/kg) or i.th. (1, 5 and 10 μg/mouse) treatments with etanercept produced dose dependent reversal of tactile allodynia in diabetic mice. However, etanercept was found to be inactive against allodynia when given i.pl. (1, 5 and 10 μg/mouse). Our results suggest that etanercept has promising effects on diabetic neuropathic pain with antiallodynic effects when given systemically or intrathecally.

Authors+Show Affiliations

Department of Pharmacology, Gulhane Military Academy of Medicine, Etlik, Ankara, Turkey. dogrula@gata.edu.trNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21104419

Citation

Dogrul, Ahmet, et al. "Systemic and Spinal Administration of Etanercept, a Tumor Necrosis Factor Alpha Inhibitor, Blocks Tactile Allodynia in Diabetic Mice." Acta Diabetologica, vol. 48, no. 2, 2011, pp. 135-42.
Dogrul A, Gul H, Yesilyurt O, et al. Systemic and spinal administration of etanercept, a tumor necrosis factor alpha inhibitor, blocks tactile allodynia in diabetic mice. Acta Diabetol. 2011;48(2):135-42.
Dogrul, A., Gul, H., Yesilyurt, O., Ulas, U. H., & Yildiz, O. (2011). Systemic and spinal administration of etanercept, a tumor necrosis factor alpha inhibitor, blocks tactile allodynia in diabetic mice. Acta Diabetologica, 48(2), 135-42. https://doi.org/10.1007/s00592-010-0237-x
Dogrul A, et al. Systemic and Spinal Administration of Etanercept, a Tumor Necrosis Factor Alpha Inhibitor, Blocks Tactile Allodynia in Diabetic Mice. Acta Diabetol. 2011;48(2):135-42. PubMed PMID: 21104419.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systemic and spinal administration of etanercept, a tumor necrosis factor alpha inhibitor, blocks tactile allodynia in diabetic mice. AU - Dogrul,Ahmet, AU - Gul,Husamettin, AU - Yesilyurt,Ozgur, AU - Ulas,Umit H, AU - Yildiz,Oguzhan, Y1 - 2010/11/23/ PY - 2010/05/13/received PY - 2010/11/03/accepted PY - 2010/11/25/entrez PY - 2010/11/26/pubmed PY - 2011/10/1/medline SP - 135 EP - 42 JF - Acta diabetologica JO - Acta Diabetol VL - 48 IS - 2 N2 - Painful diabetic neuropathy is one of the most common forms of neuropathic pain syndromes. Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated as a key pain mediator in the development and maintenance of neuropathic pain conditions. Recent studies showed that endogenous TNF-alpha production was also accelerated in neural tissues and spinal cord under chronic hyperglycemia. Thus, in this study, we investigated whether pharmacological inhibition of TNF-alpha by etanercept, a TNF-alpha antagonist, could block behavioral sign of diabetic neuropathic pain. Diabetes was induced by streptozotocin (STZ) (200 mg/kg, i.p.) in Balb-c mice and behavioral tests were performed between 45 and 60 days after STZ administration. Mechanical and thermal sensitivities were measured by a series of calibrated Von Frey filaments and hot plate test, respectively. Etanercept was given by either intravenous (i.v.), intrathecal (i.th.) or intraplantar (i.pl.) routes to the diabetic mice. Tactile allodynia, but not thermal hyperalgesia, developed in diabetic mice. Both i.v. (1, 10 and 20 mg/kg) or i.th. (1, 5 and 10 μg/mouse) treatments with etanercept produced dose dependent reversal of tactile allodynia in diabetic mice. However, etanercept was found to be inactive against allodynia when given i.pl. (1, 5 and 10 μg/mouse). Our results suggest that etanercept has promising effects on diabetic neuropathic pain with antiallodynic effects when given systemically or intrathecally. SN - 1432-5233 UR - https://www.unboundmedicine.com/medline/citation/21104419/Systemic_and_spinal_administration_of_etanercept_a_tumor_necrosis_factor_alpha_inhibitor_blocks_tactile_allodynia_in_diabetic_mice_ L2 - https://dx.doi.org/10.1007/s00592-010-0237-x DB - PRIME DP - Unbound Medicine ER -