Adenosine-A1 receptor agonist induced hyperalgesic priming type II. Issue 3 (March 2016)

• Record Type: Journal Article
• Authors: Araldi, Dioneia; Ferrari, Luiz F.; Levine, Jon D.
• Is Part Of: Pain. Volume 157:Issue 3(2016)
• Publication Date: 2016-03
• Subjects: Hyperalgesic priming -- Hyperalgesia -- A1-adenosine receptor -- αi subunit -- Chronic pain; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000000421
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: We have recently shown that repeated exposure of the peripheral terminal of the primary afferent nociceptor to the mu-opioid receptor (MOR) agonist DAMGO ([D-Ala 2, N-Me-Phe 4, Gly 5 -ol]-enkephalin acetate salt) induces a model of transition to chronic pain that we have termed type II hyperalgesic priming. Similar to type I hyperalgesic priming, there is a markedly prolonged response to subsequent administration of proalgesic cytokines, prototypically prostaglandin E2 (PGE2 ). However, type II hyperalgesic priming differs from type I in being rapidly induced, protein kinase A (PKA), rather than PKCε dependent, not reversed by a protein translation inhibitor, occurring in female as well as in male rats, and isolectin B4-negative neuron dependent. We report that, as with the repeated injection of a MOR agonist, the repeated administration of an agonist at the A1-adenosine receptor, also a Gi-protein coupled receptor, N 6 -cyclopentyladenosine (CPA), also produces priming similar to DAMGO-induced type II hyperalgesic priming. In this study, we demonstrate that priming induced by repeated exposure to this A1-adenosine receptor agonist shares the same mechanisms, as MOR-agonist induced priming. However, the prolongation of PGE2 hyperalgesia induced by repeated administration of CPA depends on G-protein αi subunit activation, differently from DAMGO-induced type II priming, in which it depends on the β/γ subunit. These data implicate a novel form of Gi-protein signaling pathway in the type II hyperalgesic priming induced by repeated administration of an agonist at A1-adenosine receptor to the peripheral terminal of the nociceptor. Abstract : The current study investigates the intracellular mechanism involved in the neuron plastic change in nociceptors produced by repeated activation of A1-adenosine Gi-protein coupled receptor, a preclinical model of chronic pain.