TY - JOUR
T1 - Evidence for the participation of peripheral α5 subunit-containing GABAA receptors in GABAA agonists-induced nociception in rats
AU - Bravo-Hernández, Mariana
AU - Feria-Morales, Luis Alberto
AU - Torres-López, Jorge Elías
AU - Cervantes-Durán, Claudia
AU - Delgado-Lezama, Rodolfo
AU - Granados-Soto, Vinicio
AU - Rocha-González, Héctor Isaac
N1 - Funding Information:
Authors greatly appreciate the technical assistance of Guadalupe C. Vidal Cantú. This work was part of the M.Sc. dissertation of Luis Alberto Feria-Morales. Mariana Bravo-Hernández and Claudia Cervantes-Durán are Conacyt fellows. Partially supported by Conacyt CB-2012/179294 (VG-S), Conacyt 154880 (HIR-G) and SIP-20140107 (HIR-G) grants.
PY - 2014/7/5
Y1 - 2014/7/5
N2 - The activation of GABAA receptor by γ-amino butyric acid (GABA) in primary afferent fibers produces depolarization. In normal conditions this depolarization causes a reduction in the release of neurotransmitters. Therefore, this depolarization remains inhibitory. However, previous studies have suggested that in inflammatory pain, GABA shifts its signaling from inhibition to excitation by an increased GABA-induced depolarization. The contribution of peripheral α5 subunit-containing GABA A receptors to the inflammatory pain is unknown. The purpose of this study was to investigate the possible pronociceptive role of peripheral α5 subunit-containing GABAA receptors in the formalin test. Formalin (0.5%) injection into the dorsum of the right hind paw produced flinching behavior in rats. Ipsilateral local peripheral pre-treatment (-10 min) with exogenous GABA (0.003-0.03 μg/paw) or common GABAA receptor agonists muscimol (0.003-0.03 μg/paw), diazepam (0.017-0.056 μg/paw) or phenobarbital (1-100 μg/paw) significantly increased 0.5% formalin-induced nociceptive behavior. The pronociceptive effects of GABA (0.03 μg/paw), muscimol (0.03 μg/paw), diazepam (0.056 μg/paw) and phenobarbital (100 μg/paw) were prevented by either the GABAA receptor antagonist bicuculline (0.01-0.1 μg/paw) or selective α5 subunit-containing GABAA receptor inverse agonist L-655,708 (0.017-0.17 μg/paw). The α5 subunit-containing GABAA receptor protein was expressed in dorsal root ganglion (DRG) and dorsal spinal cord of naïve rats. The formalin injection did not modify α5 subunit-containing GABAA receptor expression. Overall, these results suggest that peripheral α5 subunit-containing GABAA receptors play a pronociceptive role in the rat formalin test.
AB - The activation of GABAA receptor by γ-amino butyric acid (GABA) in primary afferent fibers produces depolarization. In normal conditions this depolarization causes a reduction in the release of neurotransmitters. Therefore, this depolarization remains inhibitory. However, previous studies have suggested that in inflammatory pain, GABA shifts its signaling from inhibition to excitation by an increased GABA-induced depolarization. The contribution of peripheral α5 subunit-containing GABA A receptors to the inflammatory pain is unknown. The purpose of this study was to investigate the possible pronociceptive role of peripheral α5 subunit-containing GABAA receptors in the formalin test. Formalin (0.5%) injection into the dorsum of the right hind paw produced flinching behavior in rats. Ipsilateral local peripheral pre-treatment (-10 min) with exogenous GABA (0.003-0.03 μg/paw) or common GABAA receptor agonists muscimol (0.003-0.03 μg/paw), diazepam (0.017-0.056 μg/paw) or phenobarbital (1-100 μg/paw) significantly increased 0.5% formalin-induced nociceptive behavior. The pronociceptive effects of GABA (0.03 μg/paw), muscimol (0.03 μg/paw), diazepam (0.056 μg/paw) and phenobarbital (100 μg/paw) were prevented by either the GABAA receptor antagonist bicuculline (0.01-0.1 μg/paw) or selective α5 subunit-containing GABAA receptor inverse agonist L-655,708 (0.017-0.17 μg/paw). The α5 subunit-containing GABAA receptor protein was expressed in dorsal root ganglion (DRG) and dorsal spinal cord of naïve rats. The formalin injection did not modify α5 subunit-containing GABAA receptor expression. Overall, these results suggest that peripheral α5 subunit-containing GABAA receptors play a pronociceptive role in the rat formalin test.
KW - Bicuculline
KW - GABA
KW - Inflammatory pain
KW - L-655,708
UR - http://www.scopus.com/inward/record.url?scp=84898716808&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2014.03.051
DO - 10.1016/j.ejphar.2014.03.051
M3 - Artículo
C2 - 24726872
SN - 0014-2999
VL - 734
SP - 91
EP - 97
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -