Posts Tagged ‘serotonin’

Suggestible You 3

March 19, 2017

“Suggestible You” is the title of a book by Erik Vance.  The subtitle is “The Curious Science of Your Brain’s Ability to Deceive, Transform, and Heal.  This book is about the placebo response and related phenomena.   This is the third post on this book.

Irving Kirsch took up psychology out of a philosophical curiosity about the brain.  He mentored Ted Kaptchuk, a researcher who earned a Chinese doctorate in Eastern medicine and was an expert in acupuncture and other alternative therapies.  These two set up a lab at Harvard and for a long time their names have been synonymous with placebo research.  Kaptchuk’s work spans many complicated aspects of placebo research—genetic, biochemical—but Vance’s favorite study is a relatively simple one.  He handed patients pills and told them it was a placebo.  He explained that placebos had been shown to be very effective agains all manner of conditions, and so forth.  When these patients took the pill, it still worked.  Not as well as a secret placebo—but it worked, even though the people taking it knew it wasn’t real.

Tor Wager conducted research using functional magnetic resonance imaging f(MRI).  fMRI measures blood flow in the brain.  This blood flow is used to infer brain activity.  It is captured in voxels. A single voxel has about 63,000 neurons in it (and four times as much connective).  Nevertheless, fMRI has been invaluable in gaining insights regarding the brain.  Wager used fMRI to capture the placebo effect in action.  The first experiment used electric shock.  The research participants saw either a red or a blue spiral on a screen warning them hey would get either a strong or a mild shock, which would hit between 3 and 12 seconds later to keep them off guard (and build expectation).  Wager  looked two skin creams explaining that a one was designed to reduce the  pain and the other was a placebo.  Actually both skin creams were placebos, but the research participants said they felt less pain with the “active” cream.

The second experiment used a hot metal pad that seared the skin for 20 seconds.  This time the screen just read, “Get Ready,” and then the pad heated up.  As in the first experiment, the research participants received placebo and “pain killing” creams, both of which were actually placebos.  Wager surreptitiously lowered the temperature of the heat pad on the fake “active” cream, fooling the research participants into thinking that the cream was reducing the level of pain they felt.  Then, in the last phase (as Collca had with Vance’s shocks), he kept the temperature high.  Researchers carefully recorded how much pain the subjects reported feeling, and Wager also had their fMRI brain scans.  What the research participants reported about their pain tracked perfectly with the activation of several parts of the brain associated with pain, such as the anterior cingulate cortex (which plays a role in emotions, reward systems, and empathy), the thalamus (which handles sensory perception and alertness), and the insula (which is related to consciousness and perception).  Those reporting less pain from the placebo effect showed less activity in the key pain-related brain regions.  And those who felt less of the placebo effect showed more activity.  So these research participants were not imaging less pain; they were feeling it.

More importantly, Wager observed the route that the placebo response takes from anticipation to the release of drugs inside the brain.  Pain signals normally begin in the more primitive base of the brain (relaying information from wherever in the body the pain starts) and radiate outwards.  What Ager observed was backward, with the pain signals starting in the prefrontal cortex—the most advanced logic part of the brain with executive functions—and working back to the more primitive regions.  Vance noted that this seemed to suggest a sort of collision of information:  half originating in the body as pain, and half originating in the advanced part of the brain as expectation.  Whatever comes out of that collision is what we feel.

The following summary comes directly from Vance’s book,”Pain, like any sensation, starts in the body, goes up the spine, and then travels to the deeper brain structures that distribute that information to places like the prefrontal cortex, where we can contemplate it.  Placebos, on the other hand, seem to start in the prefrontal cortex (just behind the right temple) and go backward.  They work their way to parts of the brain that handle opioids and release chemicals that dull the pain.  That also seem to tamp down activity in the parts of the brain that recognize pain in the first place.  And you feel better.  All in a fraction of a second.”

How powerful these placebo effects are varies.  In some people they barely register.  However, in others the opioid dumps can be so powerful that people become physically addicted to their own internal opioids, similar, in theory, to how people become addicted to laudanum. One theory even suggests that chronic pain might be the result of a brain addicted to its inner pharmacy, in essence, looking for a fix.

More than opioids are involved.  Over the past few decades, other brain chemical have been shown to trigger the placebo effect.    Our inner pharmacy also stocks endocannabinoids—the same chemicals found in marijuana that play an important role in pain suppression—and serotonin,  which is important intestinal movements and is the primary neurotransmitter involved in feelings of happiness and well-being.

You Have Two Brains

December 26, 2012

As do I. It was described by Byron Robinson in The Abdominal and Pelvic Brain in 1907 and named the enteric nervous system (ENS) by Johannis Langley.1 About the same time it was found that the ENS can act autonomously. When its main connection with the brain, the vagus nerve, is severed the ENS still is capable of coordinating digestion. Interest in this gut brain dropped until the field of neurogastroenterology was born in the 1990’s. It has since been learned that about 90% of the signals passing along the vagus nerve come not from the brain above, but from the ENS.2

How do these two brains compare? Both have barriers restricting blood flows to their respective brains and are supported by glial cells. The first brain consists of about 85 billion neurons; the second brain has about 500,000 neurons. 100 neurotransmitters have been identified for the first brain; 40 neurotransmitters have been identified for the second brain. Each brain produces about half of the body’s dopamine. The first brain produces 5% of all serotonin. The second brain produces 95% of all serotonin. This final comparison is quite telling. Serotonin is best known as the “feel-good” molecule. It is involved in preventing depression and in regulating sleep, appetite, and body temperature. Serotonin produced in the gut gets into the bloodstream, where it plays a role in repairing damaged cells in the liver and lungs. Moreover, it is important for the normal development of the heart, as well as in the regulation of bone density by inhibiting bone formation.

Serotonin produced in the ENS affects mood by stimulating the vagus nerve. Research has shown that stimulation of the vagus nerve can be an effective treatment for chronic depression that has failed to respond to other treatments.3 These gut to brain signals via the vagus nerve might also explain why fatty foods make us feel good. Brain scans of volunteers given a dose of fatty acids directly into the gut had a lower response to pictures and music designed to make them feel sad that a control group given saline. The fatty acid group also reported being only about half as sad as the control group.4

Stress leads the gut to increase its production of ghrelin. Ghrehlin is a hormone that makes you feel hungrier as well as reducing anxiety and depression. It stimulates the release of dopamine in the brain both directly, by directly triggering pleasure and reward pathways, and indirectly by signals triggered via the vagus nerve. At one time during our evolutionary past, the stress-busting effect of ghrelin might have been useful, but today the result of chronic stress or depression can be chronically elevated ghrelin leading to obesity.

The second brain has also been implicated in a variety of first brain disorders. In Parkinson’s disease the problems with movement and muscle control are caused not only by loss of dopamine producing cells in the first brain, but also by dopamine producing cells in the second brain due to Lewy bodies. It is even suspected that the disease starts in the second brain as the result of some trigger such as a virus, and then spreads to the brain via the vagus nerve. Similarly the characteristic plaques and tangles found in the first brains of people with Alzheimer’s are present in their second brains also.

Cells in the second brain could be used as the basis for treatments. One experimental intervention for neurodegenerative diseases involves transplanting neural stem cells into the first brain to replenish lost neurons. Harvesting these cells from the brain or spinal cord is difficult. Neural stem cells have been found in the second brain of human adults.5 These cells could be harvested using a simple endoscopic gut biopsy. This could provide a ready source of neural stem cells. One research team is planning toed them to treat diseases including Parkinson’s.

1Young, E. (2012). Alimentary thinking. New Scientist, 15 December, 39-42.

2American Journal of Gastrointestinal and Liver Physiology, vol 283, p G217.

3The British Journal of Psychiatry, vol 189, p.282.

4The Journal of Clinical Investigation, vol 121, p. 3094.

5Cell Tissue Research, vol 344, p.217.