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Changes in peripheral HCN2 channels during persistent inflammation.
Channels (Austin). 2021 12; 15(1):165-179.C

Abstract

Nociceptor sensitization following nerve injury or inflammation leads to chronic pain. An increase in the nociceptor hyperpolarization-activated current, Ih, is observed in many models of pathological pain. Pharmacological blockade of Ih prevents the mechanical and thermal hypersensitivity that occurs during pathological pain. Alterations in the Hyperpolarization-activated Cyclic Nucleotide-gated ion channel 2 (HCN2) mediate Ih-dependent thermal and mechanical hyperalgesia. Limited knowledge exists regarding the nature of these changes during chronic inflammatory pain. Modifications in HCN2 expression and post-translational SUMOylation have been observed in the Complete Freund's Adjuvant (CFA) model of chronic inflammatory pain. Intra-plantar injection of CFA into the rat hindpaw induces unilateral hyperalgesia that is sustained for up to 14 days following injection. The hindpaw is innervated by primary afferents in lumbar DRG, L4-6. Adjustments in HCN2 expression and SUMOylation have been well-documented for L5 DRG during the first 7 days of CFA-induced inflammation. Here, we examine bilateral L4 and L6 DRG at day 1 and day 3 post-CFA. Using L4 and L6 DRG cryosections, HCN2 expression and SUMOylation were measured with immunohistochemistry and proximity ligation assays, respectively. Our findings indicate that intra-plantar injection of CFA elicited a bilateral increase in HCN2 expression in L4 and L6 DRG at day 1, but not day 3, and enhanced HCN2 SUMOylation in ipsilateral L6 DRG at day 1 and day 3. Changes in HCN2 expression and SUMOylation were transient over this time course. Our study suggests that HCN2 is regulated by multiple mechanisms during CFA-induced inflammation.

Authors+Show Affiliations

Department of Biology, Georgia State University , Atlanta, Georgia.Department of Biology, Georgia State University , Atlanta, Georgia. Neuroscience Institute, Georgia State University , Atlanta, Georgia.Department of Biology, Georgia State University , Atlanta, Georgia.Neuroscience Institute, Georgia State University , Atlanta, Georgia.Neuroscience Institute, Georgia State University , Atlanta, Georgia.Department of Biology, Georgia State University , Atlanta, Georgia. Neuroscience Institute, Georgia State University , Atlanta, Georgia.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33423595

Citation

Jansen, L-A R., et al. "Changes in Peripheral HCN2 Channels During Persistent Inflammation." Channels (Austin, Tex.), vol. 15, no. 1, 2021, pp. 165-179.
Jansen LR, Forster LA, Smith XL, et al. Changes in peripheral HCN2 channels during persistent inflammation. Channels (Austin). 2021;15(1):165-179.
Jansen, L. R., Forster, L. A., Smith, X. L., Rubaharan, M., Murphy, A. Z., & Baro, D. J. (2021). Changes in peripheral HCN2 channels during persistent inflammation. Channels (Austin, Tex.), 15(1), 165-179. https://doi.org/10.1080/19336950.2020.1870086
Jansen LR, et al. Changes in Peripheral HCN2 Channels During Persistent Inflammation. Channels (Austin). 2021;15(1):165-179. PubMed PMID: 33423595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in peripheral HCN2 channels during persistent inflammation. AU - Jansen,L-A R, AU - Forster,L A, AU - Smith,X L, AU - Rubaharan,M, AU - Murphy,A Z, AU - Baro,D J, PY - 2021/1/11/entrez PY - 2021/1/12/pubmed PY - 2021/12/24/medline KW - CFA KW - DRG KW - HCN2 KW - SUMO KW - inflammation SP - 165 EP - 179 JF - Channels (Austin, Tex.) JO - Channels (Austin) VL - 15 IS - 1 N2 - Nociceptor sensitization following nerve injury or inflammation leads to chronic pain. An increase in the nociceptor hyperpolarization-activated current, Ih, is observed in many models of pathological pain. Pharmacological blockade of Ih prevents the mechanical and thermal hypersensitivity that occurs during pathological pain. Alterations in the Hyperpolarization-activated Cyclic Nucleotide-gated ion channel 2 (HCN2) mediate Ih-dependent thermal and mechanical hyperalgesia. Limited knowledge exists regarding the nature of these changes during chronic inflammatory pain. Modifications in HCN2 expression and post-translational SUMOylation have been observed in the Complete Freund's Adjuvant (CFA) model of chronic inflammatory pain. Intra-plantar injection of CFA into the rat hindpaw induces unilateral hyperalgesia that is sustained for up to 14 days following injection. The hindpaw is innervated by primary afferents in lumbar DRG, L4-6. Adjustments in HCN2 expression and SUMOylation have been well-documented for L5 DRG during the first 7 days of CFA-induced inflammation. Here, we examine bilateral L4 and L6 DRG at day 1 and day 3 post-CFA. Using L4 and L6 DRG cryosections, HCN2 expression and SUMOylation were measured with immunohistochemistry and proximity ligation assays, respectively. Our findings indicate that intra-plantar injection of CFA elicited a bilateral increase in HCN2 expression in L4 and L6 DRG at day 1, but not day 3, and enhanced HCN2 SUMOylation in ipsilateral L6 DRG at day 1 and day 3. Changes in HCN2 expression and SUMOylation were transient over this time course. Our study suggests that HCN2 is regulated by multiple mechanisms during CFA-induced inflammation. SN - 1933-6969 UR - https://www.unboundmedicine.com/medline/citation/33423595/Changes_in_peripheral_HCN2_channels_during_persistent_inflammation_ L2 - https://www.tandfonline.com/doi/full/10.1080/19336950.2020.1870086 DB - PRIME DP - Unbound Medicine ER -