strychnine and 8-(4-sulfophenyl)theophylline

We have previously reported a vibration-induced, adenosine-mediated inhibition of nociceptive dorsal horn neurons in the cat spinal cord. The present study was conducted to investigate the mechanisms of this inhibition. In vivo intracellular recording was obtained from dorsal horn neurons in the lower lumbar segments of the anaesthetized cat. Vibration (80-250 Hz for 2-3 s every 15-20 s) was applied to the glabrous skin of the toes of the hind foot using a feedback-controlled mechanical stimulator. In 32 of 43 neurons tested, vibration produced a pronounced hyperpolarization of the membrane potential. This hyperpolarization peaked at -10 mV and decayed throughout the period of the application of vibration. It was associated with a decrease in membrane resistance, had a reversal potential negative to the resting membrane potential and was Cl(-)-independent, suggesting that it was due to an increase in a K+ conductance, properties typical of the response to adenosine. This inhibitory postsynaptic potential was unaffected by intravenous administration of bicuculline, strychnine and naloxone but was blocked by iontophoretic administration of 8-sulphophenyltheophylline, a P1-purinergic receptor antagonist. These results confirm our previous finding that vibration-induced inhibition of nociceptive dorsal horn neurons is mediated via the release of an endogenous purine compound and further suggests that this inhibition involves a postsynaptic inhibitory mechanism.

Topics: Adenosine; Adenosine Monophosphate; Animals; Bicuculline; Cats; Evoked Potentials; Iontophoresis; Membrane Potentials; Naloxone; Neurons; Pain; Physical Stimulation; Purinergic Antagonists; Spinal Cord; Strychnine; Synapses; Theophylline; Vibration

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.

Topics: Adenosine; Animals; Bicuculline; Blood Pressure; Caffeine; Cats; Dipyridamole; Injections, Intravenous; Iontophoresis; Naloxone; Neurons; Spinal Cord; Strychnine; Theophylline; Vibration