Evidence that adenosine mediates the depression of spinal dorsal horn neurons induced by peripheral vibration in the cat
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Nociceptive neurons in the dorsal horn of the cat spinal cord are depressed by vibration applied to the ipsilateral hind limb. The present study investigated the pharmacological properties of this depression because of the possibility that it represents the neural basis at the spinal level for the analgesic effects of vibration in humans. Experiments were done in cats anesthetized with sodium pentobarbital and acutely spinalized at the first lumbar level. Extracellular recordings were made from nociceptive neurons in the lower lumbar segments. The depression of these neurons induced by vibration to the hindlimb was attenuated by administration of the P1-purinergic (adenosine) receptor antagonist, caffeine (20-60 mg/kg i.v.); the maximum attenuation was 100%. Effects of caffeine began within 2 min after the start of injection (1-3 min injection period), were greatest in the 10 min period after the end of injection and lasted for up to 2 hr. Importantly, another P1-purinergic receptor antagonist, which does not cross the blood-brain barrier, 8-sulphophenyltheophylline (8-16 mg/kg), had no effect on the depression when given intravenously (n = 5); however, when administered by iontophoresis 8-sulphophenyltheophylline blocked the depression in 2 of 6 units. Dipyridamole (1.0-2.0 mg/kg i.v.), an inhibitor of adenosine uptake, potentiated the depression in 2 of 5 cases. These results prompt us to suggest that depression induced by vibration may be mediated by adenosine via the activation of P1-purinergic receptors. On the other hand, the GABAA antagonist, bicuculline, failed to attenuate vibration-induced depression when administered either intravenously (0.2-0.4 mg/kg; n = 5) or by iontophoresis (n = 10) and the glycine antagonist, strychnine (0.2-0.6 mg/kg; n = 3) and the opiate antagonist, naloxone (0.1-0.4 mg/kg; n = 4) were similarly ineffective. These findings suggest that vibration-induced depression of these units occurs without involvement of bicuculline-sensitive GABA receptors, strychnine-sensitive glycine receptors and naloxone-sensitive opiate receptors. In view of the fact that vibration-induced depression is evoked synaptically, this study is the first to demonstrate in the central nervous system a synaptic response which is mediated by adenosine. In addition, we suggest that the analgesic effects of vibration in humans may be mediated at the spinal level by activation of P1-purinergic receptors.
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