在10月9日的《神经元》（Neuron）杂志上，Zylka等人研究发现，TMPase与前列腺酸性磷酸酶（PAP）的跨膜型异构体相同，不过人们对于PAP的分子结构和生理功能也不清楚。

      Zylka小组的研究表明，敲除PAP基因的小鼠有正常的急性疼痛的敏感性，而慢性炎症和神经性疼痛反应的疼痛敏感性增强。在疼痛-功能的相互关联的研究中发现：椎管注射PAP蛋白有较强的镇痛和抗痛觉过敏作用，这种作用可以延长阿片类镇痛吗啡的作用时间。PAP通过作用外-5'-核苷酸酶来抑制疼痛，具体来说，PAP可以去除外磷酸腺苷（AMP）的腺苷后激活脊髓中的A1腺苷受体。

     至此，Zylka等阐明了PAP在嘌呤核苷酸代谢和疼痛之间的分子机制和生理功能，从而提出了一种新的应用PAP治疗慢性疼痛的方法。（生物谷Bioon.com）

生物谷推荐原始出处：

Neuron，Volume 60, Issue 1, 111-122, 9 October 2008，Mark J. Zylka, Pirkko Vihko

Prostatic Acid Phosphatase Is an Ectonucleotidase and Suppresses Pain by Generating Adenosine

Mark J. Zylka1,5,,,Nathaniel A. Sowa1,5,Bonnie Taylor-Blake1,Margaret A. Twomey1,Annakaisa Herrala2,Vootele Voikar3andPirkko Vihko2,4,

1 Department of Cell and Molecular Physiology, UNC Neuroscience Center, University of North Carolina, CB #7545, Chapel Hill, NC 27599, USA
2 Department of Biological and Environmental Sciences, Division of Biochemistry, P.O. Box 56, FI-00014, University of Helsinki, Finland
3 Neuroscience Center, P.O. Box 56, FI-00014, University of Helsinki, Finland
4 Biocenter Oulu and Research Center for Molecular Endocrinology, P.O. Box 5000, FI-90014, University of Oulu, Finland

        Thiamine monophosphatase (TMPase, also known as fluoride-resistant acid phosphatase) is a classic histochemical marker of small-diameter dorsal root ganglia neurons. The molecular identity of TMPase is currently unknown. We found that TMPase is identical to the transmembrane isoform of prostatic acid phosphatase (PAP), an enzyme with unknown molecular and physiological functions. We then found that PAP knockout mice have normal acute pain sensitivity but enhanced sensitivity in chronic inflammatory and neuropathic pain models. In gain-of-function studies, intraspinal injection of PAP protein has potent antinociceptive, antihyperalgesic, and antiallodynic effects that last longer than the opioid analgesic morphine. PAP suppresses pain by functioning as an ecto-5-nucleotidase. Specifically, PAP dephosphorylates extracellular adenosine monophosphate (AMP) to adenosine and activates A₁-adenosine receptors in dorsal spinal cord. Our studies reveal molecular and physiological functions for PAP in purine nucleotide metabolism and nociception and suggest a novel use for PAP in the treatment of chronic pain.