Evidence Details for Cpa1
PMID Title Journal Year Abstract
22524543 PAPupuncture has localized and long-lasting antinociceptive effects in mouse models of acute and chronic pain. Mol Pain. 2012 Apr 23;8:28. doi: 10.1186/1744-8069-8-28. 2012 Apr 23 Acupuncture has been used for millennia to treat pain, although its efficacy and duration of action is limited. Acupuncture also has brief (1-2 h) antinociceptive effects in mice and these effects are dependent on localized adenosine A(1) receptor (A(1)R) activation. Intriguingly, adenosine 5'-monophosphate (AMP) is basally elevated near acupuncture points. This finding suggested that it might be possible to inhibit nociception for a longer period of time by injecting prostatic acid phosphatase (PAP, ACPP) into acupuncture points. PAP is an ectonucleotidase that dephosphorylates extracellular AMP to adenosine, has a long half-life in vivo and is endogenously found in muscle tissue surrounding acupuncture points. Here, we found that injection of PAP into the popliteal fossa--a space behind the knee that encompasses the Weizhong acupuncture point--had dose- and A(1)R-dependent antinociceptive effects in mouse models of acute and chronic pain. These inhibitory effects lasted up to six days following a single injection, much longer than the hour-long inhibition provided by acupuncture. Antinociception could be transiently boosted with additional substrate (AMP) or transiently blocked with an A(1)R antagonist or an inhibitor of phospholipase C. This novel therapeutic approach--which we term ""PAPupuncture""--locally inhibits pain for an extended period of time (100x acupuncture), exploits a molecular mechanism that is common to acupuncture, yet does not require acupuncture needle stimulation."

Evidence Sentence: We found that CPA transiently (2 hr) inhibited noxious thermal sensitivity in the ipsilateral hindpaw of wild-type mice but did not affect thermal sensitivity in the contralateral hindpaw (Figure 1B).
Evidence Sentence: In contrast, CPA had no effect in either hindpaw of A1R-/- mice (Figure 1B).
Evidence Sentence: Additionally, CPA did not affect mechanical sensitivity in naive (non-sensitized) wild-type or A1R-/- mice (Figure 1C).
Evidence Sentence: PAPupuncture antinociception was delayed by 1-6 hr (depending on hPAP dose; Figure 5C), consistent with hPAP working through an enzymatic process and not a pharmacological process (contrast with rapid onset following CPA injection; Figure 1B).
Evidence Sentence: To test this, we injected a selective A1R agonist, N6-cyclopentyladenosine (CPA), into the popliteal fossa of wild-type mice and A1R-/- mice while monitoring noxious thermal and mechanical sensitivity.