Does illness really start in the mind?
When dark clouds appear, or during difficult times in our lives, we may feel physically ill, with accompanying symptoms of head-aches or stomach pains. Because of this, it may seem that illness actually starts in our mind. This phenomena is beginning to be understood, as our mental condition is deeply affected by neurological factors related to our physical condition through our nervous system.
Significant progress in medical research is making it easier to analyze the relationship between mental conditions and physical illness. Some of the most cutting edge research in this field is being carried out in Japan by a group under the supervision of Prof. A. Murakami of Hokkaido University and the former president of Osaka University, Prof. Emeritus, Dr. T. Hirano. Let’s take a look at a paper published by this group in 2010, Regional neural activation defines a gateway for autoreactive T cells to cross the blood brain barrier (Y. Arima et al. (2010) Cell 148, p 447).
In this research, a currently incurable disease, multiple sclerosis (MS), was selected as a model through which to analyze the relationship between neurological issues and illness. In MS, almost all neurons are damaged, causing bodily paralysis leading to death. To analyze whether “illness starts in the mind”, several conditions were required for the experiment. In this case, the disease was induced by administering a special type of white blood cell.
Multiple sclerosis is an auto-immune disorder in which white blood cells attack the body’s own cells and proteins. This type of white blood cell is unusual since usual white blood cells protect the body by killing external infectious viruses and bacteria. In our body, through a process known as immunological tolerance, white blood cells are able to recognize cells and components belonging to their host body and refrain from attack. The special white blood cells created artificially for Dr. Hirano’s experiments lacked immunological tolerance and attacked a type of protein called myelin, which covers nerve cells to prevent leakage of electrical impulses. Attacks by these special white blood cells caused inflammation which led to the eventual death of nerve cells.
One central question regarding the mechanism of the disease is how white blood cells were able to reach the nerve cells. Usually, white blood cells cannot leak out of blood vessels near the central nervous system that houses the brain and spinal cord. However, in the case of multiple sclerosis, white blood cells leak through blood vessel to attack cells in the central nervous system. How this occurs is not clear.
Based on a series of systematic analyses, the research team finally reached a conclusion in terms of how the leak-mechanism takes place. In their experiment, the special white blood cells leaked from blood vessels near the spinal cord around the mouse’s midsection through newly created openings in the blood vessel wall. Research also revealed that this leak originated where the tail was attached to the mouse hindquarters. Motion of the tail caused weak but continuous stimulation of sensory nerve cells in the hind muscles which subsequently led to the release of a neural transmitter similar to adrenalin from a nearby sympathetic nerve cell. This adrenalin-like transmitter triggered the release of a special factor named CCL20 from blood vessels in the midsection of the mouse. CCL20 attracts white blood cells and leads them to release another factor called interleukin 6 (IL6). Inflammation of local blood vessels caused by IL6 increased vascular permeability, allowing white blood cells to leak outside where they subsequently attacked the myelin around nerve cells, sparking the onset of multiple sclerosis.
Outline of the experiment of onset of MS by Murakami et al. (Cell, (2010) 148, p447)
Based on these complicated but important findings, the research team realized that continuous irritation such as that caused by the attachment of the tail to the hindquarters of a mouse can trigger an illness in the nervous system. Such irritation may be related to mental stress which could be seen as a cause of the illness. Other incurable self-immune disorders like Lupus erythematosus and Crohn’s disease might also share a similar relationship to continuous mental (nervous) stress, expressed in compulsive behavior such as the motion of the mouse tail to its hindquarters. The research team continues their research to answer the question of whether illness truly does start in the mind.