Peripheral administration of NR2 antagonists attenuates orofacial formalin-induced nociceptive behavior in rats

Park, Min K; Lee, Ju H.; Yang, Gwi Y.; Won, Kyoung A.; Park, Yoon Y.; Bae, Yong Chul; Ahn, Dong Kuk

doi:10.1016/j.pnpbp.2011.01.018

Cited by 13 publications

(11 citation statements)

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“…Assessment of pain transmitted by trigeminal sensory pathway was evaluated by the orofacial formalin test in the rats (Park et al 2011). Rats were divided into 4 groups (8 rats in each group) and placed in a clear plastic test chamber (30 × 30 × 30 cm) with three mirrored sides.…”

Section: Methodsmentioning

confidence: 99%

Antinociceptive Effects of H3 (R-Methylhistamine) and GABAB (Baclofen)-Receptor Ligands in an Orofacial Model of Pain in Rats

et al. 2013

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The present study explored the antinociceptive effects of H3 (R-alpha-methylhistamine) and GABAB (baclofen) receptor ligands in an orofacial model of pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (50 μl, 5 %) in the upper lip region, and the number of jumps and time spent face rubbing was recorded for 40 min. Formalin produced a marked biphasic pain response; first phase, 0–10 min (jumps), and second phase, 15–40 min, (rubbing). Baclofen (50 μg) injected into the rat wiskerpad 5 min before formalin administration suppressed both phases of pain whereas R-alpha-methylhistamine (12.5 μg) abolished the first phase only. Brains were taken immediately after behavioral testing was completed. HPLC/ED analysis showed that 5-hydroxytryptamine (5-HT) turnover was increased in hippocampus, thalamus, and brain stem of all formalin groups, excepting the baclofen group in which the balance of 5-HT metabolism was restored to control values. These findings demonstrate that GABAB receptors represent peripheral targets for analgesia. Consequently, locally administered baclofen may be a useful approach in treating inflammatory trigeminal pain.

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Section: Methodsmentioning

confidence: 99%

Antinociceptive Effects of H3 (R-Methylhistamine) and GABAB (Baclofen)-Receptor Ligands in an Orofacial Model of Pain in Rats

et al. 2013

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“…Accordingly, the antinociceptive properties of KYNA were proved in animal models of pain [29,81]. Furthermore, some of the developed analogs also displayed promising results in different animal models of headache [31,[82][83][84][85]. In an earlier study we investigated two KYNA analogs where both of them proved to be effective in the formalin model of trigeminal pain [84].…”

Section: Tryptophan Metabolism and Painmentioning

confidence: 99%

Neurotransmitter and tryptophan metabolite concentration changes in the complete Freund’s adjuvant model of orofacial pain

et al. 2020

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Background: The neurochemical background of the evolution of headache disorders, still remains partially undiscovered. Accordingly, our aim was to further explore the neurochemical profile of Complete Freund's adjuvant (CFA)-induced orofacial pain, involving finding the shift point regarding small molecule neurotransmitter concentrations changes vs. that of the previously characterized headache-related neuropeptides. The investigated neurotransmitters consisted of glutamate, γ-aminobutyric acid, noradrenalin and serotonin. Furthermore, in light of its influence on glutamatergic neurotransmission, we measured the level of kynurenic acid (KYNA) and its precursors in the kynurenine (KYN) pathway (KP) of tryptophan metabolism. Methods: The effect of CFA was evaluated in male Sprague Dawley rats. Animals were injected with CFA (1 mg/ml, 50 μl/animal) into the right whisker pad. We applied high-performance liquid chromatography to determine the concentrations of the above-mentioned compounds from the trigeminal nucleus caudalis (TNC) and somatosensory cortex (ssCX) of rats. Furthermore, we measured some of these metabolites from the cerebrospinal fluid and plasma as well. Afterwards, we carried out permutation t-tests as post hoc analysis for pairwise comparison.Results: Our results demonstrated that 24 h after CFA treatment, the level of glutamate, KYNA and that of its precursor, KYN was still elevated in the TNC, all diminishing by 48 h. In the ssCX, significant concentration increases of KYNA and serotonin were found.Conclusion: This is the first study assessing neurotransmitter changes in the TNC and ssCX following CFA treatment, confirming the dominant role of glutamate in early pain processing and a compensatory elevation of KYNA with anti-glutamatergic properties. Furthermore, the current findings draw attention to the limited time interval where medications can target the glutamatergic pathways.

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“…Furthermore, some of the developed analogs also displayed promising results in different animal models of headache [31,[82][83][84][85]. In an earlier study we investigated two KYNA analogs where both of them proved to be effective in the formalin model of trigeminal pain [84].…”

Section: Tryptophan Metabolism and Migrainementioning

confidence: 99%

Neurotransmitter and tryptophan metabolite concentration changes in the Complete Freund’s adjuvant model of orofacial pain

Cseh

Veres

Körtési

et al. 2020

Preprint

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BackgroundThe neurochemical background of the evolution of headache disorders, including migraine, still remains partially undiscovered. Accordingly, our aim was to further explore the neurochemical profile of Complete Freund’s adjuvant (CFA)-induced orofacial pain, involving finding the shift point regarding small molecule neurotransmitter concentrations changes vs. that of the previously characterized migraine-related neuropeptides. The investigated neurotransmitters consisted of glutamate, γ-aminobutyric acid, noradrenalin and serotonin. Furthermore, in light of its influence on glutamatergic neurotransmission, we measured the level of kynurenic acid (KYNA) and its precursors in the kynurenine (KYN) pathway (KP) of tryptophan metabolism. Methods The effect of CFA was evaluated in male Sprague Dawley rats. Animals were injected with CFA (1 mg/ml, 50 µl/animal) into the right whisker pad. We applied high-performance liquid chromatography to determine the concentrations of the above-mentioned compounds from the trigeminal nucleus caudalis (TNC) and somatosensory cortex (ssCX) of rats. Furthermore, we measured some of these metabolites from the cerebrospinal fluid and plasma as well. Afterwards, we carried out permutation t-tests as post hoc analysis for pairwise comparison. Results Our results demonstrated that 24 h after CFA treatment, the level of glutamate, KYNA and that of its precursor, KYN was still elevated in the TNC, all diminishing by 48 h. In the ssCX, significant concentration increases of KYNA and serotonin were found. Conclusion Based on our previous findings, the elevation of KYNA may attenuate glutamate-mediated pain processing which may serve as a novel therapeutic target in headache disorders as well. Furthermore, the current findings draw attention to the limited time interval where medications can target the glutamatergic pathways because there is a clear transition to peptide mediated pain processing even from 24 h after CFA application.

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Peripheral administration of NR2 antagonists attenuates orofacial formalin-induced nociceptive behavior in rats

Cited by 13 publications

References 45 publications

Antinociceptive Effects of H3 (R-Methylhistamine) and GABAB (Baclofen)-Receptor Ligands in an Orofacial Model of Pain in Rats

Antinociceptive Effects of H3 (R-Methylhistamine) and GABAB (Baclofen)-Receptor Ligands in an Orofacial Model of Pain in Rats

Neurotransmitter and tryptophan metabolite concentration changes in the complete Freund’s adjuvant model of orofacial pain

Neurotransmitter and tryptophan metabolite concentration changes in the Complete Freund’s adjuvant model of orofacial pain

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