Until very recently, prostatic acid phophatase (PAP) was thought to be a secreted protein found only in the prostate and used as a diagnostic marker for prostate cancer. Little was known about the function of PAP in vivo, or which was its most relevant physiological substrate. The identity of thiamine monophosphatase (TMPase), a classic histochemical marker of small-diameter dorsal root ganglia neurons was also unknown.
An article in the journal Neuron now shows that TMPase is identical to the transmembrane isoform of PAP. The report also describes PAP knockout mice which have enhanced sensitivity in chronic inflammatory and neuropathic pain models. Further evidence of the involvement of PAP in nociception was provided when an intraspinal injection of PAP was shown to suppress pain as effectively as the opioid analgaesic, morphine, but with an effect that lasted much longer (3 days vs 5 hours). PAP suppresses pain by dephosphorylating extracellular adenosine monophosphate (AMP), liberating adenosine which then activates adenosine A1 receptors in dorsal spinal cord. High intrathecal doses of morphine and high doses of A1 receptor agonists cause motor impairment, but no such adverse effects were seen at the highest doses of PAP tested. PAP has a long half life in blood and the present results suggest that PAP is stable in the spinal cord and is capable of generating adenosine for days. The study suggests that modulating the activity of PAP may provide a new option for the treatment of chronic pain.