title: PAPupuncture has localized and long-lasting antinociceptive effects in mouse models of acute and chronic pain.
abstract: 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 A₁ receptor (A₁R) 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 A₁R-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 A₁R 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.
authors.affiliation: Department of Cell and Molecular Physiology, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, CB #7545, Chapel Hill, NC 27599, USA.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Hurt
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Zylka
mesh_terms: D000135:Acid Phosphatase; D015669:Acupuncture Points; D015670:Acupuncture Therapy / Q000379:methods*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy* / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010147:Pain Measurement; D017027:Protein Tyrosine Phosphatases / Q000627:therapeutic use; D043682:Receptor, Adenosine A1 / Q000378:metabolism
chemical_list: D043682:Receptor, Adenosine A1; D000249:Adenosine Monophosphate; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases