Adenosine release may mediate spinal analgesia by morphine

Spinal analgesia produced by morphine is blocked by methylxanthine adenosine receptor antagonists. In biochemical studies, morphine releases adenosine from spinal cord synaptosomes prepared from the dorsal spinal cord, as well as from the intact spinal cord in vivo. Adenosine release is reduced by intrathecal and neonatal pretreatment with capsaicin but not by intrathecal pretreatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine, indicating that adenosine originates from small-diameter primary afferent neurons but not descending monoaminergic pathways. In this Viewpoint Jana Sawynok and colleagues review the evidence supporting the hypothesis that the spinal analgesic action of morphine is due to the release of adenosine from primary afferent nerve terminals and subsequent activation of A₁ and A₂ adenosine receptors.