A novel transverse push-pull microprobe: in vitro characterization and in vivo demonstration of the enzymatic production of adenosine in the spinal cord dorsal horn.
Adenosine produces analgesia in the spinal cord and can be formed extracellularly through enzymatic conversion of adenine nucleotides. A transverse push-pull microprobe was developed and characterized to sample extracellular adenosine concentrations of the dorsal horn of the rat spinal cord. Samples collected via this sampling technique reveal that AMP is converted to adenosine in the dorsal horn. This conversion is decreased by the ecto-5'-nucleotidase inhibitor, alpha,beta-methylene ADP. Related behavioral studies demonstrate that AMP administered directly to the spinal cord can reverse the secondary mechanical hyperalgesia characteristic of the intradermal capsaicin model of inflammatory pain. The specific adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) inhibits the antihyperalgesia produced by AMP. This research introduces a novel microprobe that can be used as an adjunct sampling technique to microdialysis and push-pull cannulas. Furthermore, we conclude that AMP is converted to adenosine in the dorsal horn of the spinal cord by ecto-5'-nucleotidase and subsequently may be one source of adenosine, acting through adenosine A(1) receptors in the dorsal horn of the spinal cord, which produce antihyperalgesia.
Patterson
S L
SL
Neuroscience Graduate Program, The University of Iowa, Iowa City, Iowa 52242, USA.
Sluka
K A
KA
Arnold
M A
MA
D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000032:analysis* / Q000096:biosynthesis; D000249:Adenosine Monophosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000295:instrumentation* / Q000379:methods; D009596:Nitrophenols; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009596:Nitrophenols; D058915:Purinergic P1 Receptor Antagonists; C053907:8-cyclopentyl-1,3-dimethylxanthine; D000249:Adenosine Monophosphate; D013806:Theophylline; D015720:5'-Nucleotidase; D000241:Adenosine; D002211:Capsaicin; C024836:4-nitrophenol