Department of Cell and Molecular Physiology, UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Trends Mol Med. 2011 Apr;17(4):188-96. doi: 10.1016/j.molmed.2010.12.006. Epub 2011 Jan 13.
Adenosine receptor agonists have potent antinociceptive effects in diverse preclinical models of chronic pain. By contrast, the efficacy of adenosine and adenosine receptor agonists in treating pain in humans is unclear. Two ectonucleotidases that generate adenosine in nociceptive neurons were recently identified. When injected spinally, these enzymes have long-lasting adenosine A(1) receptor-dependent antinociceptive effects in inflammatory and neuropathic pain models. Furthermore, recent findings indicate that spinal adenosine A(2A) receptor activation can enduringly inhibit neuropathic pain symptoms. Collectively, these studies suggest the possibility of treating chronic pain in humans by targeting specific adenosine receptor subtypes in anatomically defined regions with agonists or with ectonucleotidases that generate adenosine.
腺嘌呤核苷受体激动剂在多种慢性疼痛的临床前模型中具有很强的镇痛作用。相比之下，腺嘌呤核苷和腺嘌呤核苷受体激动剂在治疗人类疼痛方面的疗效尚不清楚。最近发现了两种在伤害性神经元中产生腺嘌呤核苷的细胞外核苷酸酶。当向椎管内注射这些酶时，它们在炎症和神经病理性疼痛模型中具有持久的、依赖于腺嘌呤 A(1)受体的镇痛作用。此外，最近的研究结果表明，脊髓腺苷 A(2A)受体的激活可以持久地抑制神经病理性疼痛症状。总的来说，这些研究表明，通过在解剖学上定义的区域用激动剂或产生腺嘌呤核苷的细胞外核苷酸酶靶向特定的腺嘌呤核苷受体亚型，有可能治疗人类的慢性疼痛。
