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A distinct role for transient receptor potential ankyrin 1, in addition to transient receptor potential vanilloid 1, in tumor necrosis factor α-induced inflammatory hyperalgesia and Freund's complete adjuvant-induced monarthritis.
Arthritis Rheum. 2011 Mar; 63(3):819-29.AR

Abstract

OBJECTIVE

To investigate the involvement of transient receptor potential ankyrin 1 (TRPA1) in inflammatory hyperalgesia mediated by tumor necrosis factor α(TNFα) and joint inflammation.

METHODS

Mechanical hyperalgesia was assessed in CD1 mice, mice lacking functional TRP vanilloid 1 (TRPV1-/-) or TRPA1 (TRPA1-/-), or respective wildtype (WT) mice. An automated von Frey system was used, following unilateral intraplantar injection of TNFα or intraarticular injection of Freund's complete adjuvant (CFA). Knee swelling and histologic changes were determined in mice treated with intraarticular injections of CFA.

RESULTS

TNFα induced cyclooxygenase-independent bilateral mechanical hyperalgesia in CD1 mice. The selective TRPV1 receptor antagonist SB-366791 had no effect on mechanical hyperalgesia when it was coinjected with TNFα, but intrathecally administered SB- 366791 attenuated bilateral hyperalgesia, indicating the central but not peripheral involvement of TRPV1 receptors. A decrease in pain sensitivity was also observed in TRPV1-/- mice. Intraplantar coadministration of the TRPA1 receptor antagonist AP-18 with TNFα inhibited bilateral hyperalgesia. Intrathecal treatment with AP-18 also reduced TNFα-induced hyperalgesia. CFA-induced mechanical hyperalgesia in CD1 mice was attenuated by AP-18 (administered by intraarticular injection 22 hours after the administration of CFA). Furthermore, intraarticular CFA–induced ipsilateral mechanical hyperalgesia was maintained for 3 weeks in TRPA1 WT mice. In contrast, TRPA1-/- mice exhibited mechanical hyperalgesia for only 24 hours after receiving CFA.

CONCLUSION

Evidence suggests that endogenous activation of peripheral TRPA1 receptors plays a critical role in the development of TNFα-induced mechanical hyperalgesia and in sustaining the mechanical hyperalgesia observed after intraaarticular injection of CFA. These results suggest that blockade of TRPA1 receptors may be beneficial in reducing the chronic pain associated with arthritis.

Authors+Show Affiliations

King's College London British Heart Foundation Centre of Excellence, Waterloo Campus, London, UK.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 available

Pub Type(s)

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

Language

eng

PubMed ID

21360511

Citation

Fernandes, Elizabeth S., et al. "A Distinct Role for Transient Receptor Potential Ankyrin 1, in Addition to Transient Receptor Potential Vanilloid 1, in Tumor Necrosis Factor Α-induced Inflammatory Hyperalgesia and Freund's Complete Adjuvant-induced Monarthritis." Arthritis and Rheumatism, vol. 63, no. 3, 2011, pp. 819-29.
Fernandes ES, Russell FA, Spina D, et al. A distinct role for transient receptor potential ankyrin 1, in addition to transient receptor potential vanilloid 1, in tumor necrosis factor α-induced inflammatory hyperalgesia and Freund's complete adjuvant-induced monarthritis. Arthritis Rheum. 2011;63(3):819-29.
Fernandes, E. S., Russell, F. A., Spina, D., McDougall, J. J., Graepel, R., Gentry, C., Staniland, A. A., Mountford, D. M., Keeble, J. E., Malcangio, M., Bevan, S., & Brain, S. D. (2011). A distinct role for transient receptor potential ankyrin 1, in addition to transient receptor potential vanilloid 1, in tumor necrosis factor α-induced inflammatory hyperalgesia and Freund's complete adjuvant-induced monarthritis. Arthritis and Rheumatism, 63(3), 819-29. https://doi.org/10.1002/art.30150
Fernandes ES, et al. A Distinct Role for Transient Receptor Potential Ankyrin 1, in Addition to Transient Receptor Potential Vanilloid 1, in Tumor Necrosis Factor Α-induced Inflammatory Hyperalgesia and Freund's Complete Adjuvant-induced Monarthritis. Arthritis Rheum. 2011;63(3):819-29. PubMed PMID: 21360511.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A distinct role for transient receptor potential ankyrin 1, in addition to transient receptor potential vanilloid 1, in tumor necrosis factor α-induced inflammatory hyperalgesia and Freund's complete adjuvant-induced monarthritis. AU - Fernandes,Elizabeth S, AU - Russell,Fiona A, AU - Spina,Domenico, AU - McDougall,Jason J, AU - Graepel,Rabea, AU - Gentry,Clive, AU - Staniland,Amelia A, AU - Mountford,David M, AU - Keeble,Julie E, AU - Malcangio,Marzia, AU - Bevan,Stuart, AU - Brain,Susan D, PY - 2011/3/2/entrez PY - 2011/3/2/pubmed PY - 2013/1/25/medline SP - 819 EP - 29 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 63 IS - 3 N2 - OBJECTIVE: To investigate the involvement of transient receptor potential ankyrin 1 (TRPA1) in inflammatory hyperalgesia mediated by tumor necrosis factor α(TNFα) and joint inflammation. METHODS: Mechanical hyperalgesia was assessed in CD1 mice, mice lacking functional TRP vanilloid 1 (TRPV1-/-) or TRPA1 (TRPA1-/-), or respective wildtype (WT) mice. An automated von Frey system was used, following unilateral intraplantar injection of TNFα or intraarticular injection of Freund's complete adjuvant (CFA). Knee swelling and histologic changes were determined in mice treated with intraarticular injections of CFA. RESULTS: TNFα induced cyclooxygenase-independent bilateral mechanical hyperalgesia in CD1 mice. The selective TRPV1 receptor antagonist SB-366791 had no effect on mechanical hyperalgesia when it was coinjected with TNFα, but intrathecally administered SB- 366791 attenuated bilateral hyperalgesia, indicating the central but not peripheral involvement of TRPV1 receptors. A decrease in pain sensitivity was also observed in TRPV1-/- mice. Intraplantar coadministration of the TRPA1 receptor antagonist AP-18 with TNFα inhibited bilateral hyperalgesia. Intrathecal treatment with AP-18 also reduced TNFα-induced hyperalgesia. CFA-induced mechanical hyperalgesia in CD1 mice was attenuated by AP-18 (administered by intraarticular injection 22 hours after the administration of CFA). Furthermore, intraarticular CFA–induced ipsilateral mechanical hyperalgesia was maintained for 3 weeks in TRPA1 WT mice. In contrast, TRPA1-/- mice exhibited mechanical hyperalgesia for only 24 hours after receiving CFA. CONCLUSION: Evidence suggests that endogenous activation of peripheral TRPA1 receptors plays a critical role in the development of TNFα-induced mechanical hyperalgesia and in sustaining the mechanical hyperalgesia observed after intraaarticular injection of CFA. These results suggest that blockade of TRPA1 receptors may be beneficial in reducing the chronic pain associated with arthritis. SN - 1529-0131 UR - https://www.unboundmedicine.com/medline/citation/21360511/A_distinct_role_for_transient_receptor_potential_ankyrin_1_in_addition_to_transient_receptor_potential_vanilloid_1_in_tumor_necrosis_factor_α_induced_inflammatory_hyperalgesia_and_Freund's_complete_adjuvant_induced_monarthritis_ L2 - https://doi.org/10.1002/art.30150 DB - PRIME DP - Unbound Medicine ER -