Modulation of formalin‐induced pain‐related behaviour by clonidine and yohimbine in the Speke's hinged tortoise (Kiniskys spekii)

Abstract

The study was designed to investigate the involvement of noradrenergic and serotonergic receptor systems in the modulation of formalin-induced pain-related behaviour in the Speke's hinged tortoise. Intradermal injection of 100 μL of formalin at a dilution of 12.5% caused pain-related behaviour (hindlimb withdrawal) that lasted for a mean time of 19.28 min (monophasic response). Intrathecal administration of clonidine (α -adrenergic receptor agonist) and yohimbine (α -adrenergic receptor antagonist) at a dose of 40 μg/kg and 37.5 μg/kg or 50 μg/kg, respectively, caused a highly significant reduction in the duration of the formalin-induced pain-related behaviour. The effect of clonidine was reversed by intrathecal administration of yohimbine at a dose of 26.7 μg/kg. The effect of yohimbine at a dose of 50 μg/kg was reversed by intrathecal injection of 20 μg/kg of the serotonergic receptor antagonist methysergide maleate. When performing antagonistic reactions, the administration of the antagonist was followed immediately by that of the agonist. The study indicates that for experimental purposes, intrathecal route of drug administration through the atlanto-occipital joint is effective in tortoises. The data also suggest that testudines have noradrenergic and serotonergic systems that appear to play a role in the modulation of pain in this species.

Effects of α2A Adrenoceptors on Norepinephrine Secretion from the Locus Coeruleus during Chronic Stress-Induced Depression

“…Moreover, damage or loss of LC noradrenergic neurons could result in the decrease of NE in the central nervous system (Marien et al, 2004 ; Rommelfanger and Weinshenker, 2007 ; Weinshenker, 2008 ). In our study, we found yohimbine, α 2 -AR antagonist (Makau et al, 2016 ), significantly increased the peak value of elicited NE release from noradrenergic nerve fibers in the PVN evoked by electrical stimulation in LC in the CUMS rats. It is generally recognized that the α2-adrenergic receptors are coupled with the inhibitory guanosine triphosphate (GTP)-binding protein, which may be involved in the receptor-mediated transmembrane signaling by regulating adenylate cyclase activity (Tsuda et al, 2003 ).…”

Investigation of noradrenergic receptor system in anti-nociception using formalin test in the naked mole rat (Heterocephalus glaber)

“…Intraperitoneal administration of clonidine under formalin test responds in a similar dose dependent manner in mice and rats ( Yoon et al., 2015 ; Fukuda et al., 2006 ). Clonidine administration intrathecally also shows similar dose dependent responses under formalin test in the African marsh terrapin ( Pelomedusa subrufa ) and Speke's hinged tortoise ( Makau et al., 2014 , 2016 ); mice ( Kanui et al., 1993 ), and Sprague-Dawley rats ( Yoon et al., 2009 ).…”

“…In the current study, administration of 30 μg/kg yohimbine significantly reversed the effects of 3 μg/kg clonidine during the late phase of formalin test. Yohimbine is reported to show similar antagonistic effects to clonidine even in humans ( Charney et al., 1983 ), rats ( Normansell and Panksepp, 1985 ), marsh terrapins ( Makau et al., 2014 ) and tortoises ( Makau et al., 2016 ). Yohimbine acts by presynaptically inhibiting alpha-2 adrenergic receptors ( Mekkaw and Al-Badr, 1987 ).…”

“…Biphasic responses have been reported in monkeys ( Sharma et al., 1993 ), guinea pigs ( Leite-Panissi et al., 2001 ), mice and rats ( Kanui et al., 1993 ; Kariuki et al., 2012 ), African toad ( Ajao et al., 2007 ), and zebra fish ( Francisco et al., 2017 ). However some animals like rabbits ( Esmaeal, 2010 ), Speke's hinged tortoise ( Wambugu et al., 2010 ; Makau et al., 2016 ), marsh terrapins ( Makau et al., 2014 ), and crocodile ( Kanui et al., 1990 ) have been reported to show a monophasic response.…”

“…In African marsh terrapins ( Pelomedusa subrufa ), administration of clonidine causes a significant reduction in formalin induced pain-related behavior that is reversible with administration of its specific antagonist yohimbine ( Makau et al., 2014 ). In Speke's hinged tortoises ( Kiniskys spekii ), administration of clonidine also causes a significant reduction in the duration of formalin induced pain-related behavior ( Makau et al., 2016 ).…”