Multiple sclerosis (MS) is a disease of the central nervous system characterized by alternate relapses and progression. The relapses are believed to be the result of acute inflammatory lesions and the progression is believed to be the result of permanent damage to the nervous system. There is a high risk of relapses associated with stressful events in the patient’s life according to a recent meta-analysis, although the entire mechanism is unknown at this time.
The major stress response systems that enable the person to deal with stress, the hypophyseal-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), seem to be involved in MS. The authors propose that neuro-endocrine-immune networks bind the two major systems together to cause MS. The ANS and the HPA interact and the activation of one results in the activation of the other.
The hypothalamus is at the base of the brain and controls the HPA axis. Stress signals are sent to the pituitary to release a hormone, which stimulates the adrenal glands. The HPA system is the major system for us to deal with stress.
The autonomic nervous system was previously called the involuntary nervous system. It has two major divisions that balance each other to some extent, which are the sympathetic and the parasympathetic nervous systems. Autonomic dysfunction in MS includes bowel, bladder, and sexual dysfunction. There is increasing evidence that autonomic nervous dysfunction causes immune dysfunction.
The sympathetic nervous system branches off the spinal cord and stimulates the adrenal glands to produce the neurotransmitters epinephrine and norepinephrine, which causes the nerves to produce norepinephrine. Sympathetic norepinephrine receptors are seen on immune blood cells, such as T cells, B cells, monocytes, and natural killer cells.
The parasympathetic nervous system comes directly from the brain stem and produces the neurotransmitter acetylcholine. Parasympathetic acetylcholine receptors are seen on immune cells. The parasympathetic vagal nerve has anti-inflammatory effects.
Experimental Autoimmune Encephalomyelitis (EAE) is an animal model of MS. HPA hyporesponsiveness, with lower corticosterone levels early in the disease, leads to greater susceptibility and more severe response to EAE. On the other hand, clinical studies in MS show HPA hyperactivity and the authors hypothesize that this may be the result of late stage neurodegeneration from MS. But, there is some evidence for HPA hyperactivity to inflammation in severe MS.
There is some evidence that the ANS is protective in EAE. The authors believe there is evidence that MS is a disease of an imbalance in the autonomic nervous system with the sympathetic side not being balanced by the parasympathetic activity.
CONCLUSION: There is evidence that Multiple Sclerosis is a disease that is greatly influenced by stress with dysfunction of the Hypophyseal-Pituitary-Adrenal Axis and the autonomic nervous systems, the two systems that control how our bodies deal with stress. MS is greatly influenced by major life stresses and much more research remains to be done to clarify the relationships of these systems and immunity in Multiple Sclerosis.