Amelioration of Pain and Anxiety in Sleep-deprived Rats by Intra-amygdala Injection of Cinnamaldehyde

Overview

Journal Sleep Med X

Date 2023 Jul 10

PMID 37424741

Authors

Seyed Kaveh Hadeiy

Solomon Habtemariam

Zeinab Shankayi

Shima Shahyad

Hedayat Sahraei

Milad Asghardoust Rezaei

Farideh Bahrami

Affiliations

Soon will be listed here.

Abstract

Background: Sleep disorders are accompanied by increased anxiety and somatic pain. In addition, it has been observed that anxiety and pain have a boosting effect on each other, resulting in continued sleep disturbances. Amygdala's (CeA) central nucleus plays a crucial role in these processes. Cinnamaldehyde (Cinn) is an aromatic compound with anti-anxiety, antioxidant, and sleep-promoting properties. The present study uses sleep-deprived rats to examine the effects of an intra-CeA injection of Cinn on pain and anxiety.

Methods: Sleep deprivation (SD) was induced using the platform technique. 35 male Wistar rats were divided into five groups. Anxiety state and nociception were evaluated among groups using formalin test (F.T.), open field test (OFT), and elevated plus maze (EPM). Anxiety tests (OFT and EPM) were conducted in all groups. The first group was undergone FT without induction of SD (SDFT). The second group received SD without FT(SDFT). The third group received both SD and FT(SDFT). The treatment and vehicle groups have undergone both SD and FT in addition to the respectively intra-CeA injection of Cinn (SDFT Cinn) and Cinn vehicle (SDFT VC). The recorded behaviors were analyzed between groups using IBM SPSS 24th version.

Results: SD did not lead to any significant difference in nociceptive behaviors in FT between groups SDFT and SDFT (P ≥ 0.05). At the same time, there was a considerable discrepancy in rearing behaviors (P < 0.006) and the number of fecal boli (P < 0.004) recorded in OFM between these groups. Treatment with Cinn led to decreased nociception (P < 0.038), decreased rearing behaviors (P < 0.01), and reduced defecation (P < 0.004) in group SD + FT+ Cinn in comparison to the group SDFT. There were no differences in anxiety test results between the first and second groups (P ≥ 0.05).

Conclusion: SD can lead to elevated anxiety, while intra-CeA injection of Cinn ameliorated both perceptions of acute pain and anxiety. Besides, the conduction of FT before the anxiety test led to no disturbance in the results of anxiety tests.

Citing Articles

Transcranial Irradiation Mitigates Paradoxical Sleep Deprivation Effect in an Age-Dependent Manner: Role of BDNF and GLP-1.

Lutfy R, Essawy A, Mohammed H, Shakweer M, Salam S Neurochem Res. 2023; 49(4):919-934.

PMID: 38114728 PMC: 10902205. DOI: 10.1007/s11064-023-04071-y.

References

Ding L, Zhang C, Masood A, Li J, Sun J, Nadeem A . Protective effects of phosphodiesterase 2 inhibitor on depression- and anxiety-like behaviors: involvement of antioxidant and anti-apoptotic mechanisms. Behav Brain Res. 2014; 268:150-158. PMC: 4075066. DOI: 10.1016/j.bbr.2014.03.042. View

Tovote P, Fadok J, Luthi A . Neuronal circuits for fear and anxiety. Nat Rev Neurosci. 2015; 16(6):317-31. DOI: 10.1038/nrn3945. View

Paxinos G, Watson C, Emson P . AChE-stained horizontal sections of the rat brain in stereotaxic coordinates. J Neurosci Methods. 1980; 3(2):129-49. DOI: 10.1016/0165-0270(80)90021-7. View

Mathew S, Abraham T . In vitro antioxidant activity and scavenging effects of Cinnamomum verum leaf extract assayed by different methodologies. Food Chem Toxicol. 2005; 44(2):198-206. DOI: 10.1016/j.fct.2005.06.013. View

Sturman O, Germain P, Bohacek J . Exploratory rearing: a context- and stress-sensitive behavior recorded in the open-field test. Stress. 2018; 21(5):443-452. DOI: 10.1080/10253890.2018.1438405. View

Everson C, Laatsch C, Hogg N . Antioxidant defense responses to sleep loss and sleep recovery. Am J Physiol Regul Integr Comp Physiol. 2004; 288(2):R374-83. DOI: 10.1152/ajpregu.00565.2004. View

Pires G, Bezerra A, Tufik S, Andersen M . Effects of acute sleep deprivation on state anxiety levels: a systematic review and meta-analysis. Sleep Med. 2016; 24:109-118. DOI: 10.1016/j.sleep.2016.07.019. View

Rao P, Gan S . Cinnamon: a multifaceted medicinal plant. Evid Based Complement Alternat Med. 2014; 2014:642942. PMC: 4003790. DOI: 10.1155/2014/642942. View

Keeble J, Bodkin J, Liang L, Wodarski R, Davies M, Fernandes E . Hydrogen peroxide is a novel mediator of inflammatory hyperalgesia, acting via transient receptor potential vanilloid 1-dependent and independent mechanisms. Pain. 2008; 141(1-2):135-42. DOI: 10.1016/j.pain.2008.10.025. View

10.

Cheatle M, Foster S, Pinkett A, Lesneski M, Qu D, Dhingra L . Assessing and Managing Sleep Disturbance in Patients with Chronic Pain. Anesthesiol Clin. 2016; 34(2):379-93. DOI: 10.1016/j.anclin.2016.01.007. View

11.

Lu Y, Neugebauer V, Chen J, Li Z . Distinct contributions of reactive oxygen species in amygdala to bee venom-induced spontaneous pain-related behaviors. Neurosci Lett. 2016; 619:68-72. PMC: 5125620. DOI: 10.1016/j.neulet.2016.03.015. View

12.

Hosni A, Abdel-Moneim A, Abdel-Reheim E, Mohamed S, Helmy H . Cinnamaldehyde potentially attenuates gestational hyperglycemia in rats through modulation of PPARγ, proinflammatory cytokines and oxidative stress. Biomed Pharmacother. 2017; 88:52-60. DOI: 10.1016/j.biopha.2017.01.054. View

13.

Wu G, Chen L, Wei G, Wei G, Li Y, Zhu G . Effects of sleep deprivation on pain-related factors in the temporomandibular joint. J Surg Res. 2014; 192(1):103-11. DOI: 10.1016/j.jss.2014.05.035. View

14.

Ma Z, Turrigiano G, Wessel R, Hengen K . Cortical Circuit Dynamics Are Homeostatically Tuned to Criticality In Vivo. Neuron. 2019; 104(4):655-664.e4. PMC: 6934140. DOI: 10.1016/j.neuron.2019.08.031. View

15.

Miller B, Schultz L, Gulati A, Su A, Pletcher M . Phenotypic characterization of a genetically diverse panel of mice for behavioral despair and anxiety. PLoS One. 2011; 5(12):e14458. PMC: 3012073. DOI: 10.1371/journal.pone.0014458. View

16.

Ossipov M, Dussor G, Porreca F . Central modulation of pain. J Clin Invest. 2010; 120(11):3779-87. PMC: 2964993. DOI: 10.1172/JCI43766. View

17.

Ramos A . Animal models of anxiety: do I need multiple tests?. Trends Pharmacol Sci. 2008; 29(10):493-8. DOI: 10.1016/j.tips.2008.07.005. View

18.

Wang J, Su B, Jiang H, Cui N, Yu Z, Yang Y . Traditional uses, phytochemistry and pharmacological activities of the genus Cinnamomum (Lauraceae): A review. Fitoterapia. 2020; 146:104675. DOI: 10.1016/j.fitote.2020.104675. View

19.

Ragab Farag M, Alagawany M, Tufarelli V . In vitro antioxidant activities of resveratrol, cinnamaldehyde and their synergistic effect against cyadox-induced cytotoxicity in rabbit erythrocytes. Drug Chem Toxicol. 2016; 40(2):196-205. DOI: 10.1080/01480545.2016.1193866. View

20.

Mendes S, Sousa F, Pereira D, Ferro T, P Pereira I, Silva B . Cinnamaldehyde modulates LPS-induced systemic inflammatory response syndrome through TRPA1-dependent and independent mechanisms. Int Immunopharmacol. 2016; 34:60-70. DOI: 10.1016/j.intimp.2016.02.012. View