title: Caffeine prevents antihyperalgesic effect of gabapentin in an animal model of CRPS-I: evidence for the involvement of spinal adenosine A1 receptor.
abstract: This study was designed to determine whether 3 weeks of gabapentin treatment is effective in alleviating neuropathic pain-like behavior in animal models of complex regional pain syndrome type-I and partial sciatic nerve ligation (PSNL). We investigated the contribution of adenosine subtypes to the antihyperalgesic effect of gabapentin by examining the effect of caffeine, a non-selective adenosine A1 and A2 receptor antagonist or 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A1 subtype receptor antagonist on this effect. Neuropathic pain was produced by unilateral prolonged hind paw ischemia and reperfusion (I/R) or PSNL procedures which resulted in stimulus-evoked mechanical hyperalgesia. After procedures, animals received gabapentin (10, 30, or 100 mg/kg intraperitoneal, respectively), caffeine (10 mg/kg intraperitoneal or 150 nmol intrathecally) or DPCPX (3 µg intrathecally) alone or in combination. Mice were tested for tactile mechanical hyperalgesia at 1, 2, and 3 weeks following procedures. Gabapentin produced dose-related inhibition of mechanical hyperalgesia over a 3-week period, and this effect was blocked by concomitant caffeine or DPCPX administration 1 week after injuries. The results of this study demonstrated that the mechanism through which gabapentin produces its effect may involve the activation of adenosine A1 subtype receptor.
authors.affiliation: Post-Graduate Program of Health Sciences, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.|Experimental Neuroscience Laboratory, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.|Undergraduate Course of Medicine, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Martins
authors.affiliation: Experimental Neuroscience Laboratory, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.|Undergraduate Course of Medicine, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.
authors.forename: Marcos R B
authors.initials: MR
authors.lastname: Prado
authors.affiliation: Experimental Neuroscience Laboratory, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.|Undergraduate Course of Medicine, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Daruge-Neto
authors.affiliation: Experimental Neuroscience Laboratory, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Batisti
authors.affiliation: Post-Graduate Program of Health Sciences, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.|Experimental Neuroscience Laboratory, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.
authors.forename: Aline A
authors.initials: AA
authors.lastname: Emer
authors.affiliation: Department of Morphological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Leidiane
authors.initials: L
authors.lastname: Mazzardo-Martins
authors.affiliation: Neurobiology Laboratory of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
authors.affiliation: Post-Graduate Program of Health Sciences, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.|Experimental Neuroscience Laboratory, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.|Undergraduate Course of Medicine, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Piovezan
mesh_terms: D000588:Amines / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000077206:Gabapentin; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D012019:Reflex Sympathetic Dystrophy / Q000188:drug therapy / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D002110:Caffeine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
keywords: adenosine receptors; chronic pain; complex regional pain syndrome; neuropathic pain; partial sciatic nerve ligation