TY - JOUR
T1 - Effect of K+ channel modulators on the antiallodynic effect of gabapentin
AU - Mixcoatl-Zecuatl, Teresa
AU - Medina-Santillán, Roberto
AU - Reyes-García, Gerardo
AU - Vidal-Cantú, Guadalupe C.
AU - Granados-Soto, Vinicio
N1 - Funding Information:
This work was partially supported by an UMSNH grant. Teresa Mixcoatl-Zecuatl is a CONACYT fellow. Authors greatly appreciate the technical and bibliographic assistance of Shelle Malkmus (Anesthesiology Department, UCSD) and Hector Vázquez, respectively. Vinicio Granados-Soto is the recipient of a sabbatical fellowship from CONACYT.
PY - 2004/1/26
Y1 - 2004/1/26
N2 - The effect of K+ channel inhibitors on the antiallodynic activity induced by spinal gabapentin was assessed in rats. Ligation of L5 and L6 spinal nerves made the rats allodynic, whereas that intrathecal administration of gabapentin (25-200 μg) reduced tactile allodynia in a dose-dependent manner. Spinal pretreatment with glibenclamide (12.5-50 μg, ATP-sensitive K+ channel inhibitor), charybdotoxin (0.01-1 ng) or apamin (0.1-3 ng, large-and small-conductance Ca2+-activated K + channel blockers, respectively), but not margatoxin (0.01-10 ng, voltage-dependent K+ channel inhibitor), significantly prevented gabapentin-induced antiallodynia. Pinacidil (1-30 μg, K+ channel opener) significantly reduced nerve ligation-induced allodynia. Intrathecal glibenclamide (50 μg), charybdotoxin (1 ng) and apamin (3 ng), but not margatoxin (10 ng), significantly reduced pinacidil-induced antiallodynia. K+ channel inhibitors alone did not modify allodynia produced by spinal nerve ligation. Results suggest that gabapentin and pinacidil may activate Ca2+-activated and ATP-sensitive K+ channels in order to produce part of its spinal antiallodynic effect in the Chung model.
AB - The effect of K+ channel inhibitors on the antiallodynic activity induced by spinal gabapentin was assessed in rats. Ligation of L5 and L6 spinal nerves made the rats allodynic, whereas that intrathecal administration of gabapentin (25-200 μg) reduced tactile allodynia in a dose-dependent manner. Spinal pretreatment with glibenclamide (12.5-50 μg, ATP-sensitive K+ channel inhibitor), charybdotoxin (0.01-1 ng) or apamin (0.1-3 ng, large-and small-conductance Ca2+-activated K + channel blockers, respectively), but not margatoxin (0.01-10 ng, voltage-dependent K+ channel inhibitor), significantly prevented gabapentin-induced antiallodynia. Pinacidil (1-30 μg, K+ channel opener) significantly reduced nerve ligation-induced allodynia. Intrathecal glibenclamide (50 μg), charybdotoxin (1 ng) and apamin (3 ng), but not margatoxin (10 ng), significantly reduced pinacidil-induced antiallodynia. K+ channel inhibitors alone did not modify allodynia produced by spinal nerve ligation. Results suggest that gabapentin and pinacidil may activate Ca2+-activated and ATP-sensitive K+ channels in order to produce part of its spinal antiallodynic effect in the Chung model.
KW - Apamin
KW - Charybdotoxin
KW - Gabapentin
KW - Glibenclamide
KW - K channel
KW - Pinacidil
UR - http://www.scopus.com/inward/record.url?scp=1642464887&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2003.11.022
DO - 10.1016/j.ejphar.2003.11.022
M3 - Artículo
C2 - 14744604
AN - SCOPUS:1642464887
SN - 0014-2999
VL - 484
SP - 201
EP - 208
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -