title: Adenosine-A1 receptor agonist induced hyperalgesic priming type II.
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, N-Me-Phe, Gly-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-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.
authors.affiliation: Departments of Medicine and Oral Surgery, and Division of Neuroscience, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Dioneia
authors.initials: D
authors.lastname: Araldi
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Ferrari
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000633:toxicity; D058907:Adenosine A1 Receptor Agonists / Q000633:toxicity*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000633:toxicity; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*
chemical_list: D058907:Adenosine A1 Receptor Agonists; D043682:Receptor, Adenosine A1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine