Abstract | BACKGROUND: OBJECTIVE: In the present study, we tested whether PAP could alleviate the pain symptoms induced by bone cancer in a rat model. STUDY DESIGN: A randomized, double blind, and controlled rat animal trial. METHODS: We first established a rat CIBP model and observed the spinal expression of PAP by immunofluorescence histochemistry and Western blot. Then, PAP (0.1, 0.3, or 1 μg) was intrathecally administered in the CIBP rats in a repeated manner from 15 to 18 days (once per day) after inoculation of tumor cells. On postoperative day (POD) 18, the mechanical paw withdrawal threshold was tested for checking the dose-effect curve and ED50 of the antinociceptive effect of PAP. In an another test, a single dose of ED50 of PAP was intrathecally injected on POD 15 to observe the time course of its effect. Furthermore, 8-cyclopentyl-1,3-dipropylxanthine ( DPCPX) (3 mg/kg), an adenosine A1 receptor antagonist, or dipyridamole (DIP) (10 μg), a nucleoside transporter inhibitor, was administered to the CIBP rats for exploring the analgesic mechanisms of PAP. The concentration of extracellular adenosine was also detected by microdialysis method after intrathecal injection of PAP (0.57 μg) and DIP (10 μg) in the CIBP rats. Finally, an in vivo electrophysiological study of the CIBP rats was performed to observe whether the electrically evoked response of spinal wide-dynamic-range (WDR) neurons could be affected by PAP (0.57 μg), DIP (10 μg), or DPCPX (10 μg). RESULTS: LIMITATIONS: It's not clear whether PAP's antinociceptive effect is mediated by other signaling molecules besides the adenosine A1 receptor. In addition, the long-term antinociceptive effect of intrathecal PAP is still not clear. CONCLUSIONS: Our study demonstrated that PAP was involved in the maintenance of CIBP and could effectively suppress central sensitization by increasing spinal extracellular adenosine concentrations to exert a significant antinociceptive effect via the adenosine A1 receptor in CIBP rats. Therefore, our experiments suggest that the endogenous enzyme PAP may be a promising candidate for CIBP treatment.
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Authors | Lei Chen, Ling Zhu, Kun Wang, Wei Wang, Xiao-Peng Mei, Tao Liu, Fu-Xing Zhang, Wen Wang, Tao Chen, Yun-Qing Li |
Journal | Pain physician
(Pain Physician)
2013 Nov-Dec
Vol. 16
Issue 6
Pg. 533-46
ISSN: 2150-1149 [Electronic] United States |
PMID | 24284839
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acid Phosphatase
- prostatic acid phosphatase
- Protein Tyrosine Phosphatases
- Adenosine
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Topics |
- Acid Phosphatase
- Adenosine
(biosynthesis)
- Animals
- Blotting, Western
- Bone Neoplasms
(metabolism, pathology)
- Bone and Bones
(pathology)
- Disease Models, Animal
- Female
- Fluorescent Antibody Technique
- Injections, Spinal
- Pain
(etiology, metabolism, pathology)
- Protein Tyrosine Phosphatases
(administration & dosage)
- Rats
- Rats, Sprague-Dawley
- Spinal Cord
(drug effects, metabolism)
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