TY - JOUR
T1 - Subcutaneous, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia in the rat
AU - Caram-Salas, Nadia L.
AU - Reyes-García, Gerardo
AU - Bartoszyk, Gerd D.
AU - Araiza-Saldaña, Claudia I.
AU - Ambriz-Tututi, Mónica
AU - Rocha-González, Héctor I.
AU - Arreola-Espino, Rosaura
AU - Cruz, Silvia L.
AU - Granados-Soto, Vinicio
N1 - Funding Information:
Authors greatly appreciate the technical assistance of Guadalupe C. Vidal-Cantú and Isaí Méndez-Ocaña and bibliographic assistance of Héctor Vázquez. We kindly appreciate the technical support of Dr. Claudia González-Espinosa in the RT-PCR experiments. Nadia L. Caram-Salas, Héctor I. Rocha-González, Rosaura Arreola-Espino, Claudia I. Araiza-Saldaña and Mónica Ambriz-Tututi are CONACYT fellows. In addition, Nadia L. Caram-Salas and Claudia I. Araiza-Saldaña are the recipients of the “Apoyos Integrales para la Formación de Doctores en Ciencias” fellowship. This work is part of the Ph.D. dissertation of Nadia L. Caram-Salas. Partially supported by Conacyt grant M-43604 (SLC).
PY - 2007/11/14
Y1 - 2007/11/14
N2 - The purpose of this study was to assess the possible antiallodynic effect of asimadoline ([N-methyl-N-[1S)-1-phenyl)-2-(13S))-3-hydroxypyrrolidine-1-yl)-ethyl]-2 ,2-diphenylacetamide HCl]) and ICI-20448 ([2-[3-(1-(3,4-Dichlorophenyl-N-methylacetamido)-2-pyrrolidinoethyl)-phe noxy]acetic acid HCl]), two peripheral selective κ opioid receptor agonists, after subcutaneous, spinal and periaqueductal grey administration to neuropathic rats. Twelve days after spinal nerve ligation tactile allodynia was observed, along with an increase in κ opioid receptor mRNA expression in dorsal root ganglion and dorsal horn spinal cord. A non-significant increase in periaqueductal grey was also seen. Subcutaneous (s.c.) administration of asimadoline and ICI-204448 (1-30 mg/kg) dose-dependently reduced tactile allodynia. This effect was partially blocked by s.c., but not intrathecal, naloxone. Moreover, intrathecal administration of asimadoline or ICI-204448 (1-30 μg) reduced tactile allodynia in a dose-dependent manner and this effect was completely blocked by intrathecal naloxone. Microinjection of both κ opioid receptor agonists (3-30 μg) into periaqueductal grey also produced a naloxone-sensitive antiallodynic effect in rats. Our results indicate that systemic, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia. This effect may be a consequence of an increase in κ opioid receptor mRNA expression in dorsal root ganglion, dorsal horn spinal cord and, to some extent, in periaqueductal grey. Finally, our data suggest that these drugs could be useful to treat neuropathic pain in human beings.
AB - The purpose of this study was to assess the possible antiallodynic effect of asimadoline ([N-methyl-N-[1S)-1-phenyl)-2-(13S))-3-hydroxypyrrolidine-1-yl)-ethyl]-2 ,2-diphenylacetamide HCl]) and ICI-20448 ([2-[3-(1-(3,4-Dichlorophenyl-N-methylacetamido)-2-pyrrolidinoethyl)-phe noxy]acetic acid HCl]), two peripheral selective κ opioid receptor agonists, after subcutaneous, spinal and periaqueductal grey administration to neuropathic rats. Twelve days after spinal nerve ligation tactile allodynia was observed, along with an increase in κ opioid receptor mRNA expression in dorsal root ganglion and dorsal horn spinal cord. A non-significant increase in periaqueductal grey was also seen. Subcutaneous (s.c.) administration of asimadoline and ICI-204448 (1-30 mg/kg) dose-dependently reduced tactile allodynia. This effect was partially blocked by s.c., but not intrathecal, naloxone. Moreover, intrathecal administration of asimadoline or ICI-204448 (1-30 μg) reduced tactile allodynia in a dose-dependent manner and this effect was completely blocked by intrathecal naloxone. Microinjection of both κ opioid receptor agonists (3-30 μg) into periaqueductal grey also produced a naloxone-sensitive antiallodynic effect in rats. Our results indicate that systemic, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia. This effect may be a consequence of an increase in κ opioid receptor mRNA expression in dorsal root ganglion, dorsal horn spinal cord and, to some extent, in periaqueductal grey. Finally, our data suggest that these drugs could be useful to treat neuropathic pain in human beings.
KW - Asimadoline
KW - ICI-204448
KW - Neuropathic pain
KW - Periaqueductal grey
KW - Spinal cord
KW - κ opioid receptor agonists
UR - http://www.scopus.com/inward/record.url?scp=34848866915&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2007.06.034
DO - 10.1016/j.ejphar.2007.06.034
M3 - Artículo
C2 - 17643411
SN - 0014-2999
VL - 573
SP - 75
EP - 83
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -