Investigating the inhibition of NMDA glutamate receptors in the basolateral nucleus of the amygdala on the pain and inflammation induced by formalin in male Wistar rats

doi:10.1007/s11515-018-1491-5

Front. Biol.

2018, Vol. 13

Issue (2) : 149-155 https://doi.org/10.1007/s11515-018-1491-5

RESEARCH ARTICLE

Investigating the inhibition of NMDA glutamate receptors in the basolateral nucleus of the amygdala on the pain and inflammation induced by formalin in male Wistar rats

Nima Heidary¹, Hedayat Sahraei², Mohammad Reza Afarinesh³, Zahra Bahari⁴, Gholam Hossein Meftahi²(

)

¹. Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
². Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
³. Kerman Cognitive Research Center and Neuroscience Research Center, Institute of Neuropharmachology, Kerman University of Medical Sciences, Kerman, Iran
⁴. Department of Physiology and Biophysics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

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Abstract

BACKGROUND: The role of the amygdala in controlling emotional pain has been emphasized in several studies. In this study, the role of the NMDA glutamate receptors in the basolateral nucleus of the amygdala (BLA) in regulating inflammation and emotional pain, induced by formalin, was studied in male rats.

METHODS: Male Wistar rats, weighing 250±20 g, were injected with 20 µL of 2% formalin into the paw of the right hind limb. Memantine, at doses of 1 and 5 mg/rat, was injected bilaterally into the BLA five minutes prior to injecting formalin. Following the injection, the pain and inflammation of the paws were measured using Dubbison-Dennis and mercury immersion methods, respectively. The behavior of the animals, including licking time and foot volume, was assessed.

RESULTS: The results showed that the inactivation of the NMDA receptors in the BLA in the acute phase of pain reduced the licking time (the emotional aspect of pain). However, at a high dose (5 µg/rat), memantine exacerbates the pain induced by formalin in the chronic phase. Additionally, the inhibition of the NMDA receptors in the BLA by memantine enhanced the formalin-induced increase in foot volume (inflammation) in a dose-dependent manner.

CONCLUSION: The study showed that the NMDA glutamate receptors in the BLA are crucial for the emotional pain and inflammation in both chronic and acute phases of formalin-induced pain. However, their roles are more pronounced in the chronic phase than in the acute phase of pain.

Keywords basolateral nucleus of amygdala formalin test inflammation licking time memantine

Corresponding Author(s): Gholam Hossein Meftahi

Online First Date: 14 May 2018 Issue Date: 28 May 2018

Cite this article:

Nima Heidary,Hedayat Sahraei,Mohammad Reza Afarinesh, et al. Investigating the inhibition of NMDA glutamate receptors in the basolateral nucleus of the amygdala on the pain and inflammation induced by formalin in male Wistar rats[J]. Front. Biol., 2018, 13(2): 149-155.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-018-1491-5
https://academic.hep.com.cn/fib/EN/Y2018/V13/I2/149

Fig.1 A) Location of the cannula tips in the BLA, according to the atlas of Paxinos and Watson. The lines indicate where the cannula tips were placed. B) Actual histological verification of the cannula placements.

Fig.2 The effect of bilateral intra-BLA administration of memantine at different doses of 1 or 5 µg/rat, during the formalin test, on licking time. A two-phase response was observed after injecting formalin, where the ﬁrst phase (acute phase) lasted for up to 5 min and the secondary phase (chronic phase) occurred 20-40 min following formalin injection. Bilateral intra-BLA administration of memantine at both doses, 5 min prior to injecting formalin, inhibited the effect of formalin on the licking time in the acute phase. However, the licking time in the animals receiving intra-BLA memantine at a dose of 5 mg/rat was higher in the chronic phase than in the animals receiving saline and memantine at a dose of 1 mg/rat. The data are represented as the mean±SEM, for eight rats, *P<0.05, **P<0.01 compared to the control group. †P<0.05, ††P<0.01, compared to the vehicle group.

Fig.3 Effects of injecting the NMDA glutamate receptor antagonist, memantine, into the BLA on inﬂammation. The intra-BLA administration of memantine, at doses of 1 and 5 mg/rat, increased the volume of the foot (foot volume), caused by injecting formalin into the paw of the right hind limb. The data are represented as the mean±SEM, for eight rats, **p<0.01, ***p<0.001 compared to the control group. †††p<0.001 compared to the vehicle group.

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