The effect of intrathecal administration of gap junction blocker and GABAA agonist and/or antagonist on chemical pain behavioral responses in male rat

Authors

Abstract

 Background
and Objective: GABAergic inhibitory interneurons are distributed in spinal cord
for pain sensation, so that muscimol and bicuculline (GABAA agonist
and antagonist) reduces and enhances pain, respectively. Gap junctions (Gj) are
membrane contacts for exchanging the signaling agents and small metabolites.
Using spinal administration (i.t) of carbenoxolone (Gj blockers), this study
tried to understand the Gj and spinal GABAergic system roles on chemical pain
sensation.   Materials
ad Methods: Male Wistar rats (200-250 g) were divided into 8 groups (n=7). The drugs were
injected at 10 μl volume intrathecally including carbenoxolone (1nM), muscimol
(0.3 μg) and bicuculline (0.3 and 0.6 μg) individually or as a form of
co-treatment. Sub-plantar injection of 0.05 ml of 2.5% formalin was used and pain
related behaviors were recorded for 1 hour.   Results: Carbenoxolone and muscimol reduced pain (p < 0.01 and p < 0.05,
respectively), and bicuculline elevated
pain (p < 0.01) induced by formalin. Carbenoxolone co-treatment with muscimol reduced
pain more than each one (p < 0.05). Administration of carbenoxolone
reduced hyperalgesia induced by bicuculline (p < 0.05).    Conclusion: Muscimol
analgesic effect elevation and bicuculline hyperalgesic effect alleviation
followed by Gjs blockade might be explained when the existence of Gj is
considered between a primary inhibitory interneuron effective on a secondary
interneuron which inhibits spinal pain projection neurons. 

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