期刊
NEURON
卷 60, 期 1, 页码 111-122出版社
CELL PRESS
DOI: 10.1016/j.neuron.2008.08.024
关键词
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资金
- UNC
- The Sloan Foundation
- The Searle Scholars Program
- The Klingenstein Foundation
- The Whitehall Foundation
- Rita Allen Foundation
- NINDS [R01NS060725, F30NS063507]
- The Sigrid Juselius Foundation
- The Finnish Cancer Foundation
- The Research Council for Medicine of the Academy of Finland
- NICHD [P30NS045892]
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, anti hyperalgesic, 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 A(1)-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.
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