Adenosine A1but Not A2aReceptor Agonist Reduces Hyperalgesia Caused by a Surgical Incision in Rats

Abstract

Background. Activation of A, adenosine receptors (A(1)Rs) causesantinociception after nerve injury and inflammation. However, the roleof A(2a) adenosine receptors (A(2a)Rs) for pain processing is lessclear. In the current study, the authors investigated the role of spinaladenosine A(1)Rs and A(2a)Rs for the maintenance of mechanicalhyperalgesia in an animal model for postoperative pain.Methods: Rats with intrathecal catheters were anesthetized and underwentplantar incision. Spontaneous pain behavior and withdrawal threshold topunctuate stimulation were measured before and after administration ofintrathecal R-phenylisopropyl-adenosine (R-PIA; A(1)R agonist), 2-wp-2carbonyl-ethyl-phenylethylaminox-5X-N-ethylcarboxami- doadenosine(CGS21680; A(2a)R agonist), or vehicle. in separate groups of animals,the effects of pertussis toxin, forskohn, glibenclamide,4-aminopyridine, tetraethylamnionium, apamin, charybdotoxin, ormargatoxin on R-PIA-induced antinockeption were examined.Results: Intrathecal administration of 5 nmol R-PIA but not 10 nmolCGS21680 decreased nonevoked spontaneous pain behavior. Furthermore,intrathecal administration of R-PIA but not of CGS21680 increasedwithdrawal thresholds after incision. Pretreatment with pertussis toxinand administration of forskolin, glibenclamide, 4-aminopyridine, andtetraethylammonium inhibited R-PIA-induced antinociception. In addition,intrathecal administration of apamin, charybdotoxin, or margatoxin didnot modify mechanical hypoalgesia mediated by R-PIA.Conclusions: Spinal A(1)Rs but not A(2a)Rs play an important role in themaintenance of nonevoked and evoked pain behaviors after an incision.Furthermore, A(1)R-induced spinal antinociception is mediated byinteractions with pertussis toxin-sensitive G proteins. In addition, theopening of adenosine triphosphatesensitive K channels but not ofcalcium-activated potassium channels and voltage-gated Kv1.3 or Kv1.6channels contribute to the antinociceptive effect of A(1)R agonists.