Altered sensory behaviors in mice following manipulation of endogenous spinal adenosine neurotransmission.
Adenosine or adenosine analogs injected intrathecally (i.t.) induce significant antinociception. Recent studies support the existence of an endogenous spinal system that can modulate nociceptive input by releasing adenosine. Inhibition of adenosine metabolism by administration of an adenosine kinase inhibitor, in the present study, decreased behavior induced by putative pain neurotransmitters providing additional support for an endogenous purinergic system. Conversely, administration of high doses of methylxanthines (i.t.), adenosine receptor antagonists, induced behavior similar to that induced by pain neurotransmitters. Methylxanthine (i.t.)-induced behavior was partially inhibited by antagonists of receptors for pain neurotransmitters. These observations are consistent with the hypothesis that an endogenous purinergic system tonically modulates nociceptive input involving a variety of chemical mediators. Preliminary studies also revealed methylxanthine-induced allodynia and suggested spinal purinergic systems may have a broader role in discriminating sensory input.
College of Pharmacy, Oregon State University, Corvallis 97331, USA. g.keil@utoronto.ca
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DeLander
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D003839:Deoxyadenosines / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D003839:Deoxyadenosines; D018377:Neurotransmitter Agents; C057928:5'-amino-5'-deoxyadenosine; D013373:Substance P; C048599:N(6)-cyclopentyladenosine; C042867:spantide; D013806:Theophylline; D000241:Adenosine