Synthetic Botox might help to treat Chronic Pain

Synthetic Botox molecules might help to treat Chronic Pain

Fantastic news for the Botox’ friends, this amazing molecule is not only enhancing your appearance and making you look younger and prettier, it can also reduce pain!
This month, a group of researchers from the UCL, the University of Sheffield and the Hospital for Sick Children, published a groundbreaking study showing how a derivate of Botox can provide long-lasting pain relief in mice without adverse effects.
The researchers mixed an opioid (dermorphin) with a variant of the botox molecule to create “Derm-BOT” and the molecule SP-BOT (a substance P-modified botulinum molecule). Then, they injected these molecules into the spine of different mice and found that they target and silences pain signals from neurons in the spinal cords of mice. One of the authors of the study, Dr. Steve Hunt (from UCL Cell & Developmental Biology), explained that Derm-BOT doesn't affect muscles like the botulinum toxin used to reduce wrinkles but it does block nerve pain for up to four months without affecting normal pain responses. More positive features of Derm-BOT are that it is safe to manufacture, is non-toxic and doesn’t kill neurons. The study covered 5 years and 200 mice that were treated with a single injection of Derm-BOT, SP-BOT or morphine. The behavior of the mice was monitored to track their pain-response. Both SP-BOT and Derm-BOT have a long-lasting effect in both inflammatory and neuropathic pain model, successfully silencing neurons without cell death.
Chronic pain affects more than 25 million Americans and is related to reduced life span, anxiety, and depression. Given the current opioid crisis, aka abuse, addiction and overuse of prescribed opioid painkillers, having optional treatments for chronic pain is essential. Moreover there is little evidence that opioids have along lasting effects maybe because the body builds up a tolerance to repeated drug use over the long term. Some reports indicate that opioids may increase the body's sensitivity to pain. On the other hand, a single injection of Derm-BOT reduced mechanical hypersensitivity to the same extent as morphine. More studies in mice and a follow up on humans will help to understand and progress this new treatment that brings hope to the patients suffering chronic pain.


Reference
Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice
Maria Maiarù, Charlotte Leese, Michelangelo Certo, Irene Echeverria-Altuna, Antonina S. Mangione, Jason Arsenault, Bazbek Davletov and Stephen P. Hunt

Science Translational Medicine 18 Jul 2018:
Vol. 10, Issue 450, eaar7384
DOI: 10.1126/scitranslmed.aar7384

Can Chocolate be Good for You? The Dark and Light Side of the Force

Can Chocolate be Good for You? The Dark and Light Side of the Force
By Jesica Levingston Mac leod, PhD

It is this time of the year again: World chocolate day – the best excuse to give and more importantly to EAT a lot of chocolate. But, maybe a better gift that receiving chocolate, is to know that eating chocolate might be good for your health.

In the beginning chocolate was “created” as a medicine – a healthy beverage – around 1900 BC by Mesoamerican people. The Aztecs and Mayas gave it the name of “xocolatl”, it means bitter water, as the early preparations of the cacao seeds had an intense bitter taste. Almost one year ago, a longitudinal study, done in the US East Coast, connected eating chocolate with better cognitive function. Yay! Great news, right? The scientists gathered information over a period of 30 years (starting in 1976) from 968 subjects (aged 23-98 years) in the Syracuse-Maine area. The results showed that more frequent chocolate consumption was meaningfully associated with better performance on the global composite score, visual-spatial memory and organization, working memory, scanning and tracking, abstract reasoning, and the mini-mental state examination. Importantly, they pointed out that with the exception of working memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors across the participants.

More good news arrived last summer: an Italian research team announced that flavanol-rich chocolate improves arterial function and working memory performance counteracting the effects of sleep deprivation. The researchers investigated the effect of flavanol-rich chocolate consumption on cognitive skills and cardiovascular parameters after sleep deprivation in 32 healthy participants, who underwent two baseline sessions after one night of undisturbed sleep and two experimental sessions after one night of total sleep deprivation. Two hours before each testing session, participants were assigned to consume high or poor flavanol chocolate bars. During the tests the participants were evaluated by the psychomotor vigilance task and a working memory task, systolic blood pressure (SBP) and diastolic blood pressure (DBP), flow-mediated dilation and pulse-wave velocity. As you might know, sleep deprivation increased SBP/DBP. The result was that SBP/DBP and pulse pressure were lower after flavanol-rich treatment respect to flavanol-poor treatment sleep deprivation impaired flow-mediated dilation, flavanol-rich, but not flavanol-poor chocolate counteracted this alteration. Flavanol-rich chocolate mitigated the pulse-wave velocity increase. Also, flavanol-rich chocolate preserved working memory accuracy in women after sleep deprivation. Flow-mediated dilation correlated with working memory performance accuracy in the sleep condition.

The European Food Safety Authority accepted the following statement for cocoa products containing 200 mg of flavanols: “cocoa flavanols help maintain the elasticity of blood vessels, which contributes to normal blood flow”. This statement means that flavanol-rich chocolate counteracted vascular impairment after sleep deprivation and restored working memory performance. In another study led by Columbia University Medical Center scientists, dietary cocoa flavanols—naturally occurring bioactives found in cocoa—reversed age-related memory decline in healthy older adults. One possibility is that the improvement in cognitive performance could be due to the effects of cocoa flavonoids on blood pressure and peripheral and central blood flow. Following on this other chocolate attribute, it was shown than weekly chocolate intake may be beneficial to arterial stiffness.

But, there are some bad news! A review of 13 scientific articles on this topic, provided evidence that dark chocolate did not reduce blood pressure. However, the reviewers claimed that there was an association with increased flow-mediated vasodilatation (FMD) and moderate for an improvement in blood glucose and lipid metabolism. Specifically, their analysis showed that chocolates containing around 100 mg epicatechin can reliably increase FMD, and that cocoa flavanol doses of around 900 mg or above may decrease blood pressure if consumed over longer periods: “Out of 32 cocoa product samples analyzed, the two food supplements delivered 900 mg of total flavanols and 100 mg epicatechin in doses of 7 g and 20 g and 3 and 8 g, respectively. To achieve these doses with chocolate, you will need to consume 100 to 500 g (for 900 mg flavanols) and 50 to 200 g (for 100 mg epicatechin). Chocolate products marketed for their purported health benefits should therefore declare the amounts of total flavanols and epicatechin”. The method of manufacturing dark chocolate retains epicatechin, whereas milk chocolate does not contain substantial amounts of epicatechin.

The first epidemiological “indication” for beneficial health effects of chocolate were found in Kuna natives in Panama with low prevalence of atherosclerosis, type 2 diabetes, and hypertension. This fact correlated with their daily intake of a homemade cocoa. These traits disappear after migration to urban and changes in diet.



There are many claims about the potential health benefits of chocolate, including anti-oxidative effect by polyphenols, anti-depressant effect by high serotonin levels, inhibition of platelet aggregation and prevention of obesity-dependent insulin resistance. Chocolate contains quercetin, a powerful antioxidant that protects cells against damage from free-radicals. Chocolate also contains theobromine and caffeine, which are central nervous system stimulants, diuretics and smooth muscle relaxants, and valeric acid, which is a stress reducer. However, chocolate also contains sugar and other additives in some chocolate products that might not be so good for your health.



Oh well, maybe the love of chocolate is like any other romantic affair: blind and passionate. Apparently, the beneficial dosage is 10 g of dark chocolate per day (>70% cocoa), so enjoy it as long as the serotonin boost for rewarding yourself with a new treat last.



Happy world chocolate day!