Orexin‐1 receptors in the rostral ventromedial medulla are involved in the modulation of capsaicin evoked pulpal nociception and impairment of learning and memory

Shahsavari, Fatemeh; Abbasnejad, Mehdi; Esmaeili‐Mahani, Saeed; Raoof, Maryam

doi:10.1111/iej.12958

Cited by 5 publications

(4 citation statements)

References 52 publications

(111 reference statements)

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“…Apelin and APJs are highly expressed in the hippocampus and hypothalamus (O'Carroll et al, 2000), and their signalling has an important role in learning and memory processes. Additionally, as some studies have demonstrated, orofacial pain, specifically dental pain, is associated with cognitive impairment, affecting learning and memory (Kooshki et al, 2016; Raoof, Esmaeili‐Mahani, Abbasnejad, et al, 2015; Shahsavari et al, 2018). Changes in apoptotic biological parameters, such as an increase in the BCL2 Associated X (Bax) and B‐cell lymphoma 2 (Bcl‐2) ratio and caspase‐3 activation, have been seen in rats' hippocampus following induction of inflammatory dental nociception‐induced learning and memory impairment (Raoof, Esmaeili‐Mahani, Nourzadeh, et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Apelin signalling in the periaqueductal grey matter alleviates capsaicin‐evoked pulpal nocifensive behaviour and capsaicin‐induced spatial learning and memory impairments in rat

et al. 2023

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Aim: Pulpal pain is a common orofacial health issue that has been linked to cognitive impairment. Because of its prominent role in pain modulation and cognitive impairment, apelin (Apl) is regarded as a promising target for clinical pain management. The role of Apl in orofacial pain, however, is unknown. The purpose of this study was to determine the effects of intra-periaqueductal grey matter (PAG) administrations of Apl-13 on capsaicin-evoked pulpal nocifensive behaviour and capsaicininduced spatial learning and memory impairments in rats.Methodology: Forty-nine male Wistar rats (200-250 g) were randomly divided into seven groups (n = 7 per group). The groups included: untreated intact, capsaicin (Caps) only, three Caps+Apl groups that received different dosages of intra-PAG injection of Apl-13 (1, 2 and 3 μg/rat) 20 min prior to capsaicin application, and two Apl+antagonist groups that received Apl receptor antagonist or naloxone (a μ opioid receptor) 20 min before Apl injection. Learning and memory were assessed using the Morris water maze test. One-way analysis of variance followed by Tukey post hoc tests was used for statistical analysis. Results: Intra-PAG administration of Apl-13 significantly reduced the capsaicininduced nocifensive behaviour (p < .01). This antinociception effect was inhibited by F13A and naloxone. Apl-13 inhibited nociception-induced learning and memory deficits (p < .01). The cognitive effects were also blocked by pre-treatment administration of F13A (3 μg/rat).

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Section: Discussionmentioning

confidence: 99%

“…As shown in Table 1, the rats were divided into seven experimental groups at random (total number = 49, n = 7 per group). The sample size was calculated based on information from previous studies (Kooshki et al, 2016(Kooshki et al, , 2017Rahbar et al, 2019;Raoof et al, 2019Raoof et al, , 2022Shahsavari et al, 2018).…”

Section: Experimental Groupsmentioning

confidence: 99%

Apelin signalling in the periaqueductal grey matter alleviates capsaicin‐evoked pulpal nocifensive behaviour and capsaicin‐induced spatial learning and memory impairments in rat

et al. 2023

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“…Intradental application of capsaicin, either acute or chronic, has been shown to induce learning and memory deficits in rats (Raoof et al, 2015b;Shahsavari et al, 2018). According to Fig.…”

Section: Discussionmentioning

confidence: 99%

Blockage of ventrolateral periaqueductal gray matter cannabinoid 1 receptor increases dental pulp pain and pain-related subsequent learning and memory deficits in rats

Raoof

Sofiabadi

Haghdoost-Yazdi

et al. 2020

Behavioural Pharmacology

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Cannabinoid 1 receptor (CB1R) signaling has a pivotal role in the modulation of both pain and cognitive responses. This study aims at investigating the role of CB1R in the ventrolateral periaqueductal gray matter (vlPAG) on both pulpal pain and pain-related subsequent changes in learning and memory performances in rats. The adult male Wistar rats were cannulated in the vlPAG. The rats were pretreated by intra-vlPAG administration of selective CB1R antagonist AM-251 (2, 4 and 8 µg/rat) and vehicle dimethylsulfoxide. The drugs were microinjected 20 min before the induction of capsaicin-induced pulpalgia. The nociceptive behaviors were recorded for 40 min. Then, passive avoidance and spatial learning and memory were assessed using the shuttle box and Morris water maze tests, respectively. Following the administration of intradental capsaicin, there was a significant nociceptive response that increased after an induced blockage of CB1R by AM-251 at 4 and 8 µg. In addition, capsaicin impaired passive avoidance and spatial memory performance of rats. Microinjection of AM-251, prior to capsaicin, could dose-dependently exaggerate capsaicinrelated learning and memory deficits in both tests. The present data indicated that the vlPAG endocannabinoid system is involved in the modulation of pain signals from dental pulp. It was also accompanied by learning and memory impairments. Behavioural Pharmacology 33: 165-174

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“…Recent studies have provided evidence indicating the incidence of impaired cognitive function in individuals experiencing chronic pain (Zhang et al., 2021 ). It has also been revealed that pain can disturb memory acquisition, consolidation, and retention processes in rats (Shahsavari et al., 2018 ). The precise mechanism of action justifying these observations has not been cleared yet.…”

Section: Introductionmentioning

confidence: 99%

Methyl jasmonate ameliorates pain‐induced learning and memory impairments through regulating the expression of genes involved in neuroinflammation

Mohammadinia,

Esmaeili‐Mahani,

Abbasnejad

et al. 2024

Brain and Behavior

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ObjectiveOrofacial pain with high prevalence is one of the substantial human health issues. The importance of this matter became more apparent when it was revealed that orofacial pain, directly and indirectly, affects cognition performances. Currently, researchers have focused on investigating pharmaceutics to alleviate pain and ameliorate its subsequent cognitive impairments.DesignIn this study, the rats were first treated with the central administration of methyl jasmonate (MeJA), which is an antioxidant and anti‐inflammatory bio‐compound. After 20 min, orofacial pain was induced in the rats by the injection of capsaicin in their dental pulp. Subsequently, the animals’ pain behaviors were analyzed, and the effects of pain and MeJA treatments on rats learning and memory were evaluated/compared using the Morris water maze (MWM) test. In addition, the expression of tumor necrosis factor‐α (TNF‐α), IL‐1β, BDNF, and COX‐2 genes in the rats’ hippocampus was evaluated using real‐time polymerase chain reaction.ResultsExperiencing orofacial pain resulted in a significant decline in the rats learning and memory. However, the central administration of 20 μg/rat of MeJA effectively mitigated these impairments. In the MWM, the performance of the MeJA‐treated rats showed a two‐ to threefold improvement compared to the nontreated ones. Moreover, in the hippocampus of pain‐induced rats, the expression of pro‐inflammatory factors TNF‐α, IL‐1β, and COX‐2 significantly increased, whereas the BDNF expression decreased. In contrast, MeJA downregulated the pro‐inflammatory factors and upregulated the BDNF by more than 50%.ConclusionsThese findings highlight the notable antinociceptive potential of MeJA and its ability to inhibit pain‐induced learning and memory dysfunction through its anti‐inflammatory effect.

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Orexin‐1 receptors in the rostral ventromedial medulla are involved in the modulation of capsaicin evoked pulpal nociception and impairment of learning and memory

Abstract: The data suggest that rostral ventromedial medulla orexin-A receptors are involved in pulpal nociceptive modulation and improvement of learning and memory deficits induced by intradental application of capsaicin.

Cited by 5 publications

References 52 publications

Apelin signalling in the periaqueductal grey matter alleviates capsaicin‐evoked pulpal nocifensive behaviour and capsaicin‐induced spatial learning and memory impairments in rat

Apelin signalling in the periaqueductal grey matter alleviates capsaicin‐evoked pulpal nocifensive behaviour and capsaicin‐induced spatial learning and memory impairments in rat

Blockage of ventrolateral periaqueductal gray matter cannabinoid 1 receptor increases dental pulp pain and pain-related subsequent learning and memory deficits in rats

Methyl jasmonate ameliorates pain‐induced learning and memory impairments through regulating the expression of genes involved in neuroinflammation

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