PAPupuncture has localized and long-lasting antinociceptive effects in mouse models of acute and chronic pain

• Main Authors: Hurt Julie K (Author), Zylka Mark J (Author)
• Format: Book
• Published: SAGE Publishing, 2012-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1744-8069-8-28; 1744-8069
• Keywords: Prostatic acid phosphatase; Adenosine A1 receptor; Acupuncture; Nociception; Ectonucleotidase; Popliteal fossa; Regional anesthesia; Phospholipase C; Pathology; RB1-214
• Source: Molecular Pain, Vol 8, Iss 1, p 28 (2012)

<p>Abstract</p> <p>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 <it>in vivo</it> 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.</p>