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.

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.

[ Effect of Ducrosiaanethifolia [Dc.] Boissessential Oil on Hot Plate Model of Pain in Adult Male Rats]

Background and Purpose: Ducrosiaanethifolia is an aromatic medicinal plant native to Iran, and has been used in traditional medicine for controlling infection, reducing anxiety and pain. Since analgesic effect of this plant has not been studied experimentally, the aim of the present research is investigating the analgesic effect of Dc. essential oil.

Materials and Methods: In this experimental study, 48 adult Wistar male rats were examined. Rats were divided randomly into 6 groups [n= 8] including: control group, morphine group and Dc. essential oil group [0.06, 0.125, 0.25 and 0.5 ml/kg, IP]. Antinociceptive effects of drugs were assessed using hot plate apparatus. The results were analyzed using SPSS using one-way analysis of variance [ANOVA] followed by post hoc Tukey. Differences were considered significant at p< 0.05.

Results: The Dc. essential oil [0.5 ml/kg] significantly decreased sensitivity to painin comparison with control group. Latency to onset of pain significantly increasedby the Dc. essential oil [0.125 ml/kg] 60 and 120 minutes after injection compared with control group. Also, the Dc. essential oil [0.25ml/kg] reduced pain 120 minutes after injection in comparison with control group.

Conclusion: Based on the findings of present study, the Dc. essential oil has analgesic properties and this plant can lead to decreased sensitivity to pain at some doses in the hot plate model of pain.