The role of basolateral amygdala orexin 1 receptors on the modulation of pain and psychosocial deficits in nitroglycerin-induced migraine model in adult male rats

Background@#Migraine headaches have been associated with sensory hyperactivity and anomalies in social/emotional responses. The main objective of this study was to evaluate the potential involvement of orexin 1 receptors (Orx1R) within the basolateral amygdala (BLA) in the modulation of pain and psychosocial dysfunction in a nitroglycerin (NTG)-induced rat model of migraine. @*Methods@#Adult male Wistar rats were injected with NTG (5 mg/kg, intraperitoneal) every second day over nine days to induce migraine. The experiments were done in the following six groups (6 rats per group): untreated control, NTG, NTG plus vehicle, and NTG groups that were post-treated with intra-BLA microinjection of Orx1R antagonist SB-334867 (10, 20, and 40 nM). Thermal hyperalgesia was assessed using the hot plate and tail-flick tests. Moreover, the elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behaviors. The animals’ sociability was evaluated using the three-chamber social task. The NTG-induced photophobia was assessed using a light-dark box. @*Results@#We observed no change in NTG-induced thermal hyperalgesia following administration of SB-334867 (10, 20, and 40 nM). However, SB-334867 (20 and 40 nM) aggravated the NTG-induced anxiogenic responses in both the EPM and OF tasks. The NTG-induced social impairment was overpowered by SB-334867 at all doses. Time spent in the dark chamber of light-dark box was significantly increased in rats treated with SB-334867 (20 and 40 nM/rat). @*Conclusions@#The findings suggest a role for Orx1R within the BLA in control comorbid affective complaints with migraine in rats.

The ability of orexin-A to modify pain-induced cyclooxygenase-2and brain-derived neurotrophic factor expression is associated with its ability to inhibit capsaicin-induced pulpal nociception in rats

Background@#The rostral ventromedial medulla (RVM) is a critical region for the management of nociception. The RVM is also involved in learning and memory processes due to its relationship with the hippocampus. The purpose of the present study was to investigate the molecular mechanisms behind orexin-A signaling in the RVM and hippocampus’s effects on capsaicin-induced pulpal nociception and cog-nitive impairments in rats. @*Methods@#Capsaicin (100 g) was applied intradentally to male Wistar rats to induce inflammatory pulpal nociception. Orexin-A and an orexin-1 receptor antagonist (SB-334867) were then microinjected into the RVM. Immunoblotting and immunofluorescence staining were used to check the levels of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) in the RVM and hippocampus. @*Results@#Interdental capsaicin treatment resulted in nociceptive responses as well as a reduction in spatial learning and memory. Additionally, it resulted in decreased BDNF and increased COX-2 expression levels. Orexin-A administration (50 pmol/1 μL/rat) could reverse such molecular changes. SB-334867 microinjection (80 nM/1 μL/rat) suppressed orexin’s effects. @*Conclusions@#Orexin-A signaling in the RVM and hippocampus modulates capsaicininduced pulpal nociception in male rats by increasing BDNF expression and decreasing COX-2 expression.

Orexin-A inhibits capsaicin-induced changes in cyclooxygenase-2 and brain-derived neurotrophic factor expression in trigeminal nucleus caudalis of rats

BACKGROUND: The trigeminal nucleus caudalis (Vc) is a primary central site for trigeminal transmitting. Noxious stimulation of the trigeminal nociceptors alters the central synaptic releases and neural expression of some inflammatory and trophic agents. Orexin-A and the orexin 1 receptor (OX1R) are expressed in pain pathways including trigeminal pain transmission. However, the the mechanism(s) underling orexin-A effects on trigeminal pain modulation have not been fully clarified. METHODS: Trigeminal pain was induced by subcutaneous injection of capsaicin in the upper lip in rats. The effect of trigeminal pain on cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) expression in the Vc of animals was determined by immunofluorescence. Subsequently, OX1R agonist (orexin-A) and antagonist (SB-334867-A) was administrated in the Vc to investigate the possible roles of the Vc OX1R on changes in COX-2 and BDNF levels following pain induction. RESULTS: The data indicated an increase in COX-2 and decrease in BDNF immuno-reactivity in the Vc of capsaicin, and capsaicin- pretreated with SB-334867-A (80 nM), groups of rat. However, the effect of capsaicin on COX-2 and BDNF expressions was reversed by a Vc microinjection of orexin-A (100 pM). CONCLUSIONS: Overall, the present data reveals that orexin-A can attenuate capsaicin-induced trigeminal pain through the modulation of pain effects on COX-2 and BDNF expressions in the Vc of rats.

The effects of regular exercise on capsaicin-induced pulpal pain and pain-induced changes in passive avoidance learning and memory in rats

BACKGROUND: Pulpal pain is one of the most common and severe orofacial pain conditions with considerable adverse effects on physiological processes including learning and memory. Regular exercise is known to be effective on cognitive function as well as pain processing in the central nervous system. Here, the possible effects of regular exercise on pulpal pain response as well as pain-induced changes in learning and memory efficiency in rats were investigated. METHODS: Twenty-four male Wistar rats were randomly assigned to the control, capsaicin, exercise, and exercise plus capsaicin groups. Rats in exercise groups were forced to run on a treadmill with a moderate exercise protocol for 4 weeks. Capsaicin was used to induce dental pulp pain. Passive avoidance learning and memory performance was assessed by using a shuttle box apparatus. RESULTS: According to the results, regular exercise could decrease the time course of capsaicin-induced pulpal pain (P < 0.001). Moreover, in capsaicin-treated rats, passive avoidance acquisition was impaired as compared to the control (P < 0.05) and exercise (P < 0.001) groups. Additionally, regular exercise before capsaicin injection could attenuate capsaicin-induced memory impairments (P < 0.05). CONCLUSIONS: Taken together, the present data showed that regular exercise has inhibitory effects on capsaicin-induced pulpal pain as well as pain-induced cognitive dysfunction in rats.

Elastofibroma of the face: a case report

Elastofibroma is a rare neoplasm that characteristically occurs in subscapular area in response to microtrauma. There are some reports of this tumor in other sites of the body but, up till now, there has been no report of elastofibroma in the face. A 20-year-old man presented with a slow growing painless mass in the face without any history of trauma. Histopathologic examination revealed a soft tissue mass composed of eosinophilic fibers admixed with aggregation of fat cells, capillary blood vessels, and fibroblasts. Elastic stain and Masson's trichrome stain confirmed the nature of elastic and collagen fibers. It was a case of elastofibroma in the face

Surface microhardness of three thicknesses of mineral trioxide aggregate in different setting conditions

OBJECTIVES: This study aimed to compare the surface microhardness of mineral trioxide aggregate (MTA) samples having different thicknesses and exposed to human blood from one side and with or without a moist cotton pellet on the other side. MATERIALS AND METHODS: Ninety cylindrical molds with three heights of 2, 4, and 6 mm were fabricated. In group 1 (dry condition), molds with heights of 2, 4, and 6 mm (10 molds of each) were filled with ProRoot MTA (Dentsply Tulsa Dental), and the upper surface of the material was not exposed to any additional moisture. In groups 2 and 3, a distilled water- or phosphate-buffered saline (PBS)-moistened cotton pellet was placed on the upper side of MTA, respectively. The lower side of the molds in all the groups was in contact with human blood-wetted foams. After 4 day, the Vickers microhardness of the upper surface of MTA was measured. RESULTS: In the dry condition, the 4 and 6 mm-thick MTA samples showed significantly lower microhardness than the 2 mm-thick samples (p = 0.003 and p = 0.001, respectively). However, when a distilled water- or PBS-moistened cotton pellet was placed over the MTA, no significant difference was found between the surface microhardness of samples having the abovementioned three thicknesses of the material (p = 0.210 and p = 0.112, respectively). CONCLUSIONS: It could be concluded that a moist cotton pellet must be placed over the 4 to 6 mm-thick MTA for better hydration of the material. However, this might not be necessary when 2 mm-thick MTA is used.