Chronic ghrelin treatment reduced photophobia and anxiety‐like behaviors in nitroglycerin‐ induced migraine: role of pituitary adenylate cyclase‐activating polypeptide

Chronic migraine is a debilitating disorder that has a significant impact on patients and society. Nearly all migraineurs frequently reported light sensitivity during a headache attack. Pituitary adenylate cyclase‐activating polypeptide (PACAP) plays an important role in the activation of trigeminal system and migraine pain. To identify the effect of chronic ghrelin treatment on endogenous PACAP and associated symptoms of migraine, an experimental chronic migraine model was induced by intermittent intraperitoneal (i.p) injection of nitroglycerin (NTG). Photophobia and anxiety‐like behaviors were determined in the modified elevated plus maze on days 2, 4, 6, 8, and 10 and in the light/dark box on days 3, 5, 7, 9, and 11. Blood levels of PACAP and cortisol were assessed by enzyme‐linked immunosorbent (ELISA) kits. Chronic injection of NTG evoked photophobia and anxiety‐like behaviors and treatment with ghrelin (150 μg/kg) for 11 days effectively attenuated photophobia and anxiety‐like behaviors in the both paradigms. We further found that NTG increased the blood levels of PACAP and cortisol, which was significantly reduced by ghrelin treatment. Additionally, staining with Hematoxylin and Eosin (H&E) revealed that ghrelin reduced NTG‐induced increase in the number of satellite glial cells in the trigeminal ganglion. Furthermore, for the first time we showed that repeated administrations of NTG increased white blood cell (WBC) counts and mean platelet volume (MPV), and decreased platelet counts. These results indicated that ghrelin decreased migraine associated symptoms possibly through attenuating endogenous PACAP and cortisol levels. Therefore, ghrelin may hold therapeutic potentialities in managing the chronic migraine.     

Opiates and plasticity

Opiates are among the most powerful analgesics and pain-relieving agents. However, they are potentially extremely addictive thereby limiting their medical use, making them exceedingly susceptible to abuse and adding to the global drug problem. It is believed that positive memories associated with the pleasurable effects of opiates and negative memories associated with dysphoria during opiate withdrawal contribute to compulsive opiate-seeking behavior characterizing addiction. There is a vast amount of available data regarding the neuroadaptations in response to opiates during opiate tolerance, dependence and withdrawal that contribute to opiate addiction, yet it is still a major challenge to identify the neurobiological adaptations that underlie the hallmarks of opiate addiction such as compulsive drug use, and relapse to drug seeking. Since the discovery of synaptic plasticity as the cellular correlate of learning and memory, strong overlaps between neural and cellular substrates of learning and addiction have been recognized. Consequently, the current notion of addiction supports the idea that aberrant forms of drug-induced synaptic plasticity and learning in the brain drive addictive behaviors. Here we discuss current progress on some of the recently identified forms of synaptic plasticity at excitatory and inhibitory synapses in opioid-sensitive areas of the brain that are targeted by opiates and other addictive drugs. The neuroadaptations involved in opiate tolerance, dependence and withdrawal will be re-visited since they share many features with synaptic learning mechanisms.This article is part of a Special Issue entitled ‘Synaptic Plasticity and Addiction’.     

The glucocorticoid system is required for the voluntary exercise-induced enhancement of learning and memory in rats

Although it is well established that voluntary exercise can improve cognitive functions, the underlying mechanisms are largely unknown. Glucocorticoids play an important role in learning and memory functions. This study addressed whether the glucocorticoid system would play a role in the exercise-induced enhancement of learning and memory. Intact rats or those that were either adrenalectomized or daily given the corticosterone-synthesis inhibitor metyrapone were allowed to freely exercise in a running wheel for 10 days. Control animals were kept sedentary for this period. After this period, they were trained and tested on a water-maze spatial task using three-trial per day for 5 consecutive days, succeeded by a probe trial two days later. Exercise increased plasma corticosterone levels, as assessed after this 10-day period. Both adrenalectomy and metyrapone slightly reduced running-wheel activity. Adrenalectomy reduced the plasma corticosterone levels to almost zero whereas metyrapone selectively blocked the exercise-induced increase in corticosterone levels. Exercise significantly improved performance during both training and retention of the water-maze task whereas this effect was absent in both adrenalectomized and metyrapone-treated rats. These findings indicate that the glucocorticoid system play a crucial role in the beneficial effects of voluntary exercise on cognitive functions in rats.     

Itraconazole,a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth

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Highlights? Itraconazole identified as Hh pathway inhibitor in screen of human-experienced drugs ? Itraconazole appears to act on Smoothened at distinct site from cyclopamine ? Itraconazole inhibits accumulation of Smoothened in primary cilium ? Itraconazole suppresses Hh-dependent tumor growth in vivo     

Episiotomy pain relief: Use of Lavender oil essence in primiparous Iranian women

Introduction

Post-episiotomy discomfort and its consequences can affect maternal quality of life and mental health as well as the mother and baby relationship. Complementary medicine is increasingly used and Lavender oil is frequently prescribed due to its antiseptic and healing properties.

Method

This clinical trial involved 60 qualified primiparous women admitted for labor in Kamali Hospital in Karaj, Iran. They were randomly categorized into two groups: case (using Lavender oil) and control (usual hospital protocol). Participants pain and discomfort were recorded using a Visual Analogue Scale (VAS) and a Redness, Edema, Ecchymosis, Discharge Scale (REEDA). Pain was evaluated at 4 h, 12 h and 5 days following episiotomy. Collected data was analyzed in SPSS 14 using an independent t-test and chi-square.

Results

There was a statistical difference in pain intensity scores between the 2 groups after 4 h (p = 0.002, and 5 days (p = 0.000) after episiotomy. However, differences in pain intensity between the two groups, at 12 h post-surgery, were not significant (p = 0.066). The REEDA score was significantly lower in the experimental group (Lavender oil group) 5 days after episiotomy (p = 0.000).

Conclusion

According to these findings, use of Lavender oil essence can be effective in reducing perineal discomfort following episiotomy. It is suggested that Lavender oil essence may be preferably to the use of Betadine for episiotomy wound care.