Zahn Peter K, Straub Heidrun, Wenk Manuel, Pogatzki-Zahn Esther M
Department for Anaesthesiology and Operative Intensive Care, University of Muenster, Muenster, Germany.
Anesthesiology. 2007 Nov;107(5):797-806. doi: 10.1097/01.anes.0000286982.36342.3f.
Activation of A1 adenosine receptors (A1Rs) causes antinociception after nerve injury and inflammation. However, the role of A2a adenosine receptors (A2aRs) for pain processing is less clear. In the current study, the authors investigated the role of spinal adenosine A1Rs and A2aRs for the maintenance of mechanical hyperalgesia in an animal model for postoperative pain.
Rats with intrathecal catheters were anesthetized and underwent plantar incision. Spontaneous pain behavior and withdrawal threshold to punctuate stimulation were measured before and after administration of intrathecal R-phenylisopropyl-adenosine (R-PIA; A1R agonist), 2-w p-2-carbonyl-ethyl-phenylethylaminox-5X-N-ethylcarboxami-doadenosine (CGS21680; A2aR agonist), or vehicle. In separate groups of animals, the effects of pertussis toxin, forskolin, glibenclamide, 4-aminopyridine, tetraethylammonium, apamin, charybdotoxin, or margatoxin on R-PIA-induced antinociception were examined.
Intrathecal administration of 5 nmol R-PIA but not 10 nmol CGS21680 decreased nonevoked spontaneous pain behavior. Furthermore, intrathecal administration of R-PIA but not of CGS21680 increased withdrawal thresholds after incision. Pretreatment with pertussis toxin and administration of forskolin, glibenclamide, 4-aminopyridine, and tetraethylammonium inhibited R-PIA-induced antinociception. In addition, intrathecal administration of apamin, charybdotoxin, or margatoxin did not modify mechanical hypoalgesia mediated by R-PIA.
Spinal A1Rs but not A2aRs play an important role in the maintenance of nonevoked and evoked pain behaviors after an incision. Furthermore, A1R-induced spinal antinociception is mediated by interactions with pertussis toxin-sensitive G proteins. In addition, the opening of adenosine triphosphate-sensitive K channels but not of calcium-activated potassium channels and voltage-gated Kv1.3 or Kv1.6 channels contribute to the antinociceptive effect of A1R agonists.
A1腺苷受体（A1Rs）激活可在神经损伤和炎症后引起抗伤害感受。然而，A2a腺苷受体（A2aRs）在疼痛处理中的作用尚不清楚。在本研究中，作者在术后疼痛动物模型中研究了脊髓腺苷A1Rs和A2aRs在维持机械性痛觉过敏中的作用。
将带有鞘内导管的大鼠麻醉后行足底切口。在鞘内注射R-苯异丙基腺苷（R-PIA；A1R激动剂）、2-对-2-羰基-乙基-苯乙胺氧基-5-X-N-乙基羧酰胺腺苷（CGS21680；A2aR激动剂）或赋形剂前后，测量自发疼痛行为和对点状刺激的撤针阈值。在单独的动物组中，检测百日咳毒素、福斯高林、格列本脲、4-氨基吡啶、四乙铵、蜂毒明肽、蝎毒素或玛格毒素对R-PIA诱导的抗伤害感受的影响。
鞘内注射5 nmol R-PIA而非10 nmol CGS21680可减少非诱发性自发疼痛行为。此外，鞘内注射R-PIA而非CGS21680可提高切口后的撤针阈值。百日咳毒素预处理以及福斯高林、格列本脲、4-氨基吡啶和四乙铵的给药可抑制R-PIA诱导的抗伤害感受。此外，鞘内注射蜂毒明肽、蝎毒素或玛格毒素不会改变R-PIA介导的机械性痛觉减退。
脊髓A1Rs而非A2aRs在切口后非诱发性和诱发性疼痛行为的维持中起重要作用。此外，A1R诱导的脊髓抗伤害感受是通过与百日咳毒素敏感的G蛋白相互作用介导的。此外，三磷酸腺苷敏感性钾通道的开放而非钙激活钾通道以及电压门控Kv1.3或Kv1.6通道的开放有助于A1R激动剂的抗伤害感受作用。
