Systemic agmatine attenuates tactile allodynia in two experimental neuropathic pain models in rats

Karadağ, Çetin Hakan; Ulugöl, Ahmet; Tamer, Melek; İpçi, Yeşim; Dökmeci, İsmet

doi:10.1016/s0304-3940(02)01456-8

Cited by 41 publications

(35 citation statements)

References 15 publications

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“…However several reports found that NOS is not related to allodynia in neuropathic pain models. 30,31) Lee et al 30) reported that a potent neuronal NOS inhibitor did not reduce mechanical sensitivity in spinal nerve ligated rats, and that neither the anti-allodynic nor the preemptive effects of L-NAME were mediated by NOS inhibition.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Agmatine on GABA_AReceptor Antagonist-induced Tactile Allodynia

Lee

Ishikawa

2008

Korean J Pain

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Background: The intrathecal (IT) GABAA receptor antagonist, bicuculline (BIC), results in tactile allodynia (TA) through disinhibition in the spinal cord. Such disinhibition is considered to be an important mechanism for neuropathic pain. Agmatine, an endogenous polyamine, has a neuro-protective effect in the central nervous system. We investigated the analgesic effects and mechanisms of agmatine action on BIC-induced TA.Methods: Male Sprague-Dawley rats, weighting 250−300 g, were subjected to implantations of PE-10 into the lumbar subarachnoid space for IT drug injection. Five days after surgery, either 10μl of normal saline (NS) or agmatine (30μg or 10μg) in 10μl NS were injected 10 min prior to BIC (10μg) or NMDA (5μg). We assessed the degree of TA (graded 0: no response, 1: mild response, 2: moderate response, 3: strong response) every 5 min for 30 min. Areas under curves and degree of TA were expressed as mean ± SEM. Results were analyzed using one-way ANOVA followed by a Tukey test for multiple comparisons. P ＜ 0.05 was considered significant.Results: IT BIC-induced strong TA reached its peak and plateaued between 10 to 15 min. IT NS-NMDA induced mild transient TA for up to 15 min. Preemptive IT AG attenuated IT BIC-induced TA dose dependently and preemptive IT AG10 completely abolished the IT NMDA-induced TA.Conclusions: Preemptive IT AG attenuated the IT BIC-induced TA through inhibitory actions on postsynaptic NMDA receptor activation. AG might be a viable therapeutic option in the treatment of neuropathic pain. (Korean J Pain 2008; 21: 173-178)

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Section: Discussionmentioning

confidence: 99%

“…Additionally, Karadag et al 31) reported that agmatine reduced mechanical allodynia at high doses, but that MK-801 and the NOS inhibitors, such as N(G)-nitro-L-arginine methyl ester and 7-nitroindazole, did not influence the antiallodynic effects of agmatine. These results suggest that agmatine has a non-neuronal action site.…”

Section: Discussionmentioning

confidence: 99%

Effects of Agmatine on GABA_AReceptor Antagonist-induced Tactile Allodynia

Lee

Ishikawa

2008

Korean J Pain

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“…Likewise, no effect of AG was reported in naive animals stimulated with von Frey filaments (Karadag et al, 2003) and in the warm water tail-immersion test or against substance P-evoked nociceptive behavior or in response to thermal stimulus of noninflamed paw in carrageenan-treated rats (Horvà th et al, 1999). However, a previously published study (Hou et al, 2003) indicates that similar i.t.…”

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confidence: 94%

“…Antinociceptive properties of AG were also reported in both acute and chronic pain models, in particular, neuropathic pain. Karadag et al (2003) showed that AG reversed tactile allodynia in spinal nerve ligation and in streptozocin (STZ)-induced diabetes models. Fairbanks et al (2000) also reported the antiallodynic and antihyperalgesic effect of AG in rats with ligated spinal nerve.…”

Section: Introductionmentioning

confidence: 99%

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Agmatine Induces Antihyperalgesic Effects in Diabetic Rats and a Superadditive Interaction with R(–)-3-(2-Carboxypiperazine-4-yl)-propyl-1-phosphonic Acid, a N-Methyl-d-aspartate-Receptor Antagonist

Courteix

Privat

Hernández³

et al. 2007

J Pharmacol Exp Ther

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Agmatine, an endogenous cationic amine resulting from the decarboxylation of L-arginine, produces antihyperalgesic and antiallodynic effects in animal models of chronic neuropathic and inflammatory pain. We examined the effect of agmatine on tactile and thermal allodynia and on mechanical hyperalgesia in streptozocin-induced diabetic rats. To determine its mechanism of action and the potential interest of some of its combinations, the antihyperalgesic effect of agmatine was challenged with ␣ 2 -adrenergic imidazoline and opioid-receptor antagonists, and its interaction with the opioid-receptor agonist morphine, the competitive N-methyl-D-aspartate receptor antagonist D-CPP [R(Ϫ)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid], and the nitric-oxide synthase inhibitor L-NAME (L-N G -nitro-L-arginine methyl ester) were examined. When intrathecally (i.t.) injected (4.4 to 438 nmol/rat), agmatine was ineffective in normal rats but suppressed tactile allodynia (von Frey hair test), thermal allodynia (tail immersion test), and mechanical hyperalgesia (paw-pressure test) in diabetic rats. This spinal antihyperalgesic effect was suppressed by idazoxan (40 mol/rat i.t.) but not by yohimbine (40 mol/rat i.t.) or naloxone (0.69 mol/rat i.v.). In diabetic rats, an isobolographic analysis showed that combinations of i.t. agmatine with i.v. L-NAME or with i.t. morphine resulted in an additive antihyperalgesic effect, whereas the agmatine/D-CPP i.t. combination was superadditive. In summary, the present findings reveal that spinal agmatine produces antiallodynic and antihyperalgesic effects in diabetic neuropathic pain involving, at least for its antihyperalgesic effect, the imidazoline receptors. Moreover, agmatine combined with D-CPP produces an antinociceptive synergy in experimental neuropathy, opening opportunities in the development of new strategies for pain therapy.Agmatine (AG; 4-(aminobutyl) guanidine) is an endogenous cationic amine obtained from the decarboxylation of L-arginine by the enzyme arginine decarboxylase. The distribution of AG-containing neurons is concentrated in brain regions involved in pain processing (Reis and Regunathan, 2000) and in all areas of the spinal cord gray matter . AG was described as a neuroprotective agent in experimental models of neurotrauma and excitotoxic disorders (Gilad et al., 1996;Fairbanks et al., 2000;Yu et al., 2000). Antinociceptive properties of AG were also reported in both acute and chronic pain models, in particular, neuropathic pain. Karadag et al. (2003) showed that AG reversed tactile allodynia in spinal nerve ligation and in streptozocin (STZ)-induced diabetes models. Fairbanks et al. (2000) also reported the antiallodynic and antihyperalgesic effect of AG in rats with ligated spinal nerve. In rats with chronic constriction nerve injury, thermal allodynia and hyperalgesia and mechanical hyperalgesia (Ö nal et al., 2003) were dose-dependently reduced by AG.

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An ethopharmacological assessment of agmatine's effects on agonistic encounters between male mice

Navarro

Luna

2005

Aggr. Behav.

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The endogenous polyamine agmatine may be a new central neurotransmitter. Agmatine-like immunoreactivity has been described in numerous brain regions (such as the hypothalamus and amygdala), long thought involved in the control of aggression. Consequently, the present study examined agmatine's (2.5-80 mg/kg, ip) effects on behavior directed by isolated male mice to anosmic partners in a neutral area. The videotaped encounters were analysed in terms of 10 broad behavioral categories. Agmatine did not appear to be involved in the modulation of aggression or anxiety in this test. Aggr. Behav. 31:374-380, 2005. r

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Systemic agmatine attenuates tactile allodynia in two experimental neuropathic pain models in rats

Cited by 41 publications

References 15 publications

Effects of Agmatine on GABA_AReceptor Antagonist-induced Tactile Allodynia

Effects of Agmatine on GABA_AReceptor Antagonist-induced Tactile Allodynia

Agmatine Induces Antihyperalgesic Effects in Diabetic Rats and a Superadditive Interaction with R(–)-3-(2-Carboxypiperazine-4-yl)-propyl-1-phosphonic Acid, a N-Methyl-d-aspartate-Receptor Antagonist

An ethopharmacological assessment of agmatine's effects on agonistic encounters between male mice

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Systemic agmatine attenuates tactile allodynia in two experimental neuropathic pain models in rats

Cited by 41 publications

References 15 publications

Effects of Agmatine on GABAAReceptor Antagonist-induced Tactile Allodynia

Effects of Agmatine on GABAAReceptor Antagonist-induced Tactile Allodynia

Agmatine Induces Antihyperalgesic Effects in Diabetic Rats and a Superadditive Interaction with R(–)-3-(2-Carboxypiperazine-4-yl)-propyl-1-phosphonic Acid, a N-Methyl-d-aspartate-Receptor Antagonist

An ethopharmacological assessment of agmatine's effects on agonistic encounters between male mice

Contact Info

Product

Resources

About

Effects of Agmatine on GABA_AReceptor Antagonist-induced Tactile Allodynia

Effects of Agmatine on GABA_AReceptor Antagonist-induced Tactile Allodynia