Alteration in sensitivity of ionotropic glutamate receptors and tachykinin receptors in spinal cord contribute to development and maintenance of nerve injury-evoked neuropathic pain.
Allodynia or hyperalgesia induced by peripheral nerve injury may be involved in changes in the sensitivity of neurotransmitters at the spinal cord level. In order to clarify the functional role of neurotransmitters in peripheral nerve injury, we used rats with nerve injury induced by chronic constriction of the sciatic nerve (CCI rat model) and estimated the effects of the intrathecal injection of drugs known to affect glutamate and tachykinin receptors. In sham-operated rats, the NMDA receptor agonist NMDA and AMPA-kinate receptor agonist RS-(5)-bromowillardin reduced withdrawal latency. The non-competitive NMDA receptor antagonist MK-801, competitive NMDA receptor antagonist AP-5 and AMPA-kinate receptor antagonist NBQX increased withdrawal latency. Substance P (SP) increased the withdrawal latency but only transitorily. The NK1 receptor antagonist RP67580 increased withdrawal latency, but the NK2 receptor antagonist SR48968 did not show an effect. In CCI rats, RS-(5)-bromowillardin reduced withdrawal latency, but NMDA did not show an effect. NBQX increased withdrawal latency, while MK-801 and AP-5 showed little or no effect. SP reduced withdrawal latency, and both RP67580 and SR48968 increased it. These results indicate that the alteration in sensitivity of ionotropic glutamate receptors and tachykinin receptors in the spinal cord contribute to development and maintenance of nerve injury-evoked neuropathic pain.
Yoshimura
Masakazu
M
Central Research Laboratory of Maruishi Pharmaceutical Co Ltd, 2-2-18 Imazunaka, Osaka, Japan.
Yonehara
Norifumi
N
D000409:Alanine / Q000031:analogs & derivatives / Q000378:metabolism; D000700:Analgesics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001549:Benzamides / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D054833:Isoindoles; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism; D010146:Pain / Q000378:metabolism*; D010147:Pain Measurement; D010880:Piperidines / Q000378:metabolism; D011810:Quinoxalines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018039:Receptors, Tachykinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism / Q000601:surgery; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives / Q000378:metabolism
D000409:Alanine; D000700:Analgesics; D001549:Benzamides; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D054833:Isoindoles; D016202:N-Methylaspartate; D010880:Piperidines; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018039:Receptors, Tachykinin; D013373:Substance P; D014633:Valine; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C068592:5-bromowillardiine; C073839:SR 48968; C056639:2-amino-5-phosphopentanoic acid