Effects of a novel piperazine derivative (CGP 29030A) on nociceptive dorsal horn neurons in the rat.
In anaesthetized rats and cats, the effects of the piperazine derivative CGP 29030A on the discharges of functionally identified dorsal horn neurons and gamma-motoneurons was studied. The compound exhibited a marked inhibitory action on presumably nociceptive dorsal horn neurons that processed input from high-threshold mechanosensitive receptors in the skin and deep somatic tissues (muscle, tendon, joint). Significant effects were obtained at a dose of 10 mg/kg p.o. and higher; the onset of action was fast (approximately 10 min). In contrast to presumably nociceptive dorsal horn neurons, cells having input from low-threshold mechanosensitive receptors in the skin and deep tissues were not affected by the compound. Thus CGP 29030A has a quite specific action on dorsal horn neurons that probably mediate pain. Systemic effects on the blood pressure and on the activity of sympathetic efferent fibres did not occur. The lack of effect of CGP 29030A on nociceptive neurons in spinalized animals suggests that the site of action is not the segmental spinal cord but the supraspinal CNS. gamma-motoneurons supplying the gastrocnemius-soleus muscle were likewise inhibited by the compound but at a higher dose (equal to and exceeding 30 mg/kg). The data show that CGP 29030A is a compound with marked and specific analgesic action. As it also inhibits gamma-motoneurons, CGP 29030A may be of benefit in the treatment of painful disorders which are complicated by increased motor activity (cramp, spasm).
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Institute for Anatomy and Cell Biology, Heidelberg University, Germany.
Hoheisel
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Mense
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D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects*; D006801:Humans; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D010879:Piperazines; C082998:CGP 29030A