The effects of pretreatment with tachykinin antagonists and galanin on the development of spinal cord hyperexcitability following sciatic nerve section in the rat.
The effects of acute section of the sciatic nerve on the excitability of the flexor reflex was examined in decerebrate, spinalized, unanaesthetized rats. In control experiments without drugs, the excitability of the flexor reflex was dramatically increased in two phases following axotomy. An early intense, brief reflex hyperexcitability was followed by a less intense, prolonged period of facilitation. The selective NK1 tachykinin receptor antagonist CP-96,345 injected intrathecally at lower (1.2-2.4 nmol) and higher (12 nmol) doses blocked both components of spinal sensitization. The selective NK2 tachykinin receptor antagonist Men 10376 at a dose of 2.4 nmol also reduced both response components, as did the same dose of the inhibitory neuropeptide galanin. Thus, antagonists of excitatory neuropeptides released during and after nerve section, such as substance P and neurokinin A, can block the spinal response to peripheral nerve injury. Furthermore, the inhibitory neuropeptide galanin also reduced spinal cord sensitization.
Luo
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Karolinska Institute, Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Wiesenfeld-Hallin
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D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002422:Causalgia / Q000503:physiopathology*; D004558:Electric Stimulation; D005260:Female; D019004:Galanin; D006987:Hypesthesia / Q000503:physiopathology; D007278:Injections, Spinal; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000187:drug effects* / Q000502:physiology; D012021:Reflex, Abnormal / Q000187:drug effects*; D012584:Sciatic Nerve / Q000293:injuries*; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D015320:Tachykinins / Q000037:antagonists & inhibitors*
D001713:Biphenyl Compounds; D010446:Peptide Fragments; D010455:Peptides; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D015288:Neurokinin A; D019004:Galanin; C066892:CP 96345