ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Animals , Rats , Brain-Derived Neurotrophic Factor , Capsaicin , Cyclooxygenase 2 , Facial Pain , Fluorescent Antibody Technique , Injections, Subcutaneous , Lip , Microinjections , Nociceptors , Orexin Receptor Antagonists , Orexins , Pain Measurement , Pain Perception , Trigeminal Caudal Nucleus , Trigeminal Neuralgia , Trigeminal NucleiABSTRACT
Introduction: The neuroprotective role of opioid morphine against 6-hydroxydopamine-induced cell death has been demonstrated. However, the exact mechanism[s] underlying such neuroprotection, especially the role of subtype receptors, has not yet been fully clarified
Methods: Here, we investigated the effects of different opioid agonists on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson's disease. Cell damage was induced by 150 micro M 6-OHDA and the cells viability was examined by MTT assay. Intracellular calcium, reactive oxygen species and mitochondrial membrane potential were assessed by fluorescence spectrophotometry method. Immunoblot technique was used to evaluate cytochrome-c and activated caspase-3 as biochemical markers of apoptosis induction
Results: The data showed that 6-OHDA caused significant cell damage, loss of mitochondrial membrane potential and increase in intracellular reactive oxygen species and calcium levels as well as activated caspase-3 and cytochrome-c release. Incubation of SH-SY5Y cells with sigma -opioid agonists, morphine and DAMGO, but not with sigma-opioid agonist, DADLE, elicited protective effect and reduced biochemical markers of cell damage and death
Discussion: The results suggest that sigma-opioid receptors signaling participate in the opioid neuroprotective effects against 6-OHDA-induced neurotoxicity
ABSTRACT
Ascorbic acid [AA] is not synthesized in the brain but it is actively transported through blood-brain barrier by SVCT2 cotransporter and it is stored in high concentrations with heterogeneous distribution in areas such as nucleus accumbens shell [AcbSh] in the mammalian brain. Previous studies have shown that Ascorbic acid injection into AcbSh decreases feeding; therefore, in the present study we evaluated the effects of oral Ascorbic acid pretreatment on changes in feeding upon its injection in AcbSh in adult male rats. Sixty-three adult male rats [220-280 g] were divided into five treatment and five pretreatment groups. The treatment groups included the control [intact] group, sham-operated Ascorbic acid group that received normal saline as vehicle, and three other groups that received different doses of ascorbic acid [10, 50 and 250 microg/rat] by injection into AcbSh for four days. The pretreatment groups received Ascorbic acid [100 mg/kg] for 15 days via gastric gavage before receiving the aforementioned doses in treatment groups into intra nucleus AcbSh. Feeding measurement was repeated every 12 hours by automatic metabolic cage. The results indicated that all injected doses of Ascorbic acid [10, 50 and 250 microg/rat] into nucleus accumbens shell decrease food intake [P<0.05] in rats and oral Ascorbic acid pretreatment had no effects in this regard. Our findings show that ascorbic acid is an effective factor in feeding regulation. Oral pretreatment seems to have no influence on the central effects of ascorbic acid in the nucleus accumbens shell