Antinociceptive and modulatory effect of pathoplastic changes in spinal glia of a TLR4/CD14 blocking molecule in two models of pain in rat - 27/05/22
Abstract |
The role of spinal glia in the development and maintenance of chronic pain has become over the last years a subject of increasing interest. In this regard, toll-like receptor 4 (TLR4) signaling has been proposed as a major trigger mechanism. Hence, in this study we explored the implications of TLR4 inhibition in the periphery and primarily in the CNS, focusing on the impact this inhibition renders in pain development and glia activation in the dorsal horn in two models of pain. Making use of a synthetic cluster of differentiation 14 (CD14)/TLR4 antagonist, the effect of TLR4 blockade on tactile allodynia and heat hyperalgesia was evaluated in osteoarthritic and postoperative rat models. An in vitro parallel artificial membrane permeation assay was performed to determine the proneness of the drug to permeate the blood-brain barrier prior to systemic and central administration. Findings suggest a dominant role of peripheral TLR4 in the model of incisional pain, whilst both peripheral and central TLR4 seem to be responsible for osteoarthritic pain. That is, central and peripheral TLR4 may be differently involved in the etiopathology of diverse types of pain what potentially seems a promising approach in the management of pain.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Glia is involved in the development and maintenance of chronic pain. |
• | TLR4 receptors could be the trigger that initiates glial activation. |
• | Central and peripheral TLR4 receptors participate differently in the etiology of pain. |
• | Peripheral and central TLR4 appear to be involved in osteoarthritic pain. |
• | Peripheral TLR4 appear to be involved in incisional pain. |
Abbreviations : TLR4, MD-2, PAMPA-BBB, CD14, OA, MIA, i.a., PO, TLR4-A1, BBB, PBS, PBL, i.p., i.t., Iba-1, GFAP, DAB, CNS, BL
Keywords : Osteoarthritic pain, Postoperative pain, Monosodium Iodoacetate (MIA), Incision, Toll-like receptor 4 (TLR4), Astrocytes, Microglia, Rat
Plan
☆ | This research was funded by the Ministry of Economy and Competitiveness of Spain [Grant SAF2012-40075-C02-02]. Synthesis of TLR4-A1 was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (MICINN, Programa Estatal de I+D+i Orientada a los Retos de la Sociedad [Projects PID2019-105117RR-C22 and PID2019-104070RB-C21]). The PAMPA assay was performed with a grant from the Spanish Ministry of Science, Innovation and Universities, and General Council for Research and Innovation of the Community of Madrid [Grants RTI2018-093955-B-C21, B2017/BMD-3827] (both with European Structural Funds, to María Isabel Rodríguez-Franco). |
Vol 150
Article 112986- juin 2022 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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