Involvement of spinal NK2 and NMDA receptors in aversive behavior induced by intra-arterial injection of capsaicin.
The spinal processing by which intra-arterial injection of capsaicin (CAP) induces vocalization response (VOR) was investigated in guinea pigs. Intrathecal pre-treatment with CP-96,345 (a selective NK(1) receptor antagonist, 50 nmol) did not affect the CAP-induced VOR. However, significant attenuation of the VOR was observed by intrathecal pre-treatment with a selective NK(2) receptor antagonist MEN-10,376 (40 nmol) accompanied with a significant change in the response modality. MK-801 [an N-methyl-D-aspartate (NMDA) receptor antagonist, 20 and 40 nmol] inhibited the CAP-induced VOR dose-dependently without affecting the response modalities. Furthermore, intrathecal co-treatment with 40-nmol MEN-10,376 and 40-nmol MK-801 resulted in a marked inhibitory effect on the VOR followed by a significant alteration of response modalities. Intrathecal pre-treatment with neurokinin A (NKA; a tachykinin NK(2) receptor agonist, 1 nmol) enhanced the CAP-induced VOR. These behavioral results suggested that spinal NK(2) and NMDA receptors might have priority over NK(1) receptors in the spinal processing of nociceptive information from the CAP-sensitive nociceptor.
Ando
R
R
Center for Laboratory Animal Science, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan. rando@tohoku-pharm.ac.jp
Watanabe
C
C
Kawamura
S
S
Yonezawa
A
A
Sakurada
T
T
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005263:Femoral Artery; D006168:Guinea Pigs; D006614:Hindlimb / Q000294:innervation / Q000502:physiology; D007269:Injections, Intra-Arterial; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000503:physiopathology* / Q000523:psychology; D010446:Peptide Fragments / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D014828:Vocalization, Animal / Q000187:drug effects
D001713:Biphenyl Compounds; D018691:Excitatory Amino Acid Antagonists; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D018041:Receptors, Neurokinin-2; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D016291:Dizocilpine Maleate; D015288:Neurokinin A; D002211:Capsaicin; C066892:CP 96345