Involvement of adenosine in antinociception produced by spinal or supraspinal receptor-selective opioid agonists: Dissociation from gastrointestinal effects in mice

G. E. DeLander, H. I. Mosberg, Frank Porreca

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Abstract

Possible involvement of adenosine, as a secondary neurotransmitter, in opioid modulation of nociception and gastrointestinal function was investigated in mice. Inhibitory actions of theophylline, a nonselective adenosine receptor antagonist, were evaluated against effects evoked by opioid receptor-selective agonists administered at spinal or supraspinal sites. Intrathecal administration of theophylline significantly inhibited antinociceptive actions produced by intrathecal (i.th.) injections of morphine, [D-Ala2, NMPhe4, Gly-ol] enkephalin (DAMGO), [D-Pen2, D-Pen5] enkephalin (DPDPE) and β-endorphin as measured with the warm water tail- flick assay. The rank order of rightward displacement of i.th. agonist dose- response curves by theophylline (i.th.) was DPDPE (greatest) > DAMGO > morphine > β-endorphin. Theophylline was less effective as an inhibitor in the hot-plate assay. Additionally, i.th. administration of theophylline inhibited antinociceptive effects evoked by i.c.v. administration of opioids. The rank order of rightward displacement of dose-response curves after i.c.v. opioid administration was DAMGO (greatest) > β-endorphin > morphine > DPDPE. In contrast to the effectiveness of theophylline administered i.th., theophylline coadministered i.c.v. with opioid agonists did not inhibit opioid-induced antinociception. Neither i.th. nor i.c.v. theophylline altered inhibitory effects on gastric emptying and gastrointestinal propulsion produced by i.th. or i.c.v. administration of selective opioid agonists. These data provide additional support for involvement of spinal adenosine as a secondary neurotransmitter in opioid antinociceptive processes associated with local spinal reflexes as well as in descending antinociceptive processes. Adenosine was not involved in modulation of opioid-activated gastrointestinal outflow pathways at either spinal or supraspinal levels.

Original languageEnglish (US)
Pages (from-to)1097-1104
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume263
Issue number3
Publication statusPublished - 1992
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology

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