Histaminergic Basis of Central Fatigue in Multiple Sclerosis - A Novel Approach

Inclusion Criteria for Healthy Volunteers: 1. Male or female subjects between the ages of 18 and 60 will be eligible. 2. Subjects should be in good physical health without history of chronic illness and should be generally considered healthy. 3. Spouses or caregivers of patients with MS would be encouraged to participate. Inclusion Criteria for Patients with Multiple Sclerosis (MS): 1. Patients with MS regardless of the disease type, who experience severe fatigue will be eligible to participate. 2. Fatigue Severity Score of \>/= 4.0 will qualify as long as all other inclusion / exclusion criteria are met. 3. Established MS by McDonald Criteria - 2010 Revision (24). Relapse Remitting (RR) and progressive forms of MS are eligible 4. Severe fatigue that has lasted greater than 6 months 5. Clinically stable on a current therapy with any Disease Modifying Therapy (DMT) Exclusion Criteria for Healthy Volunteers: 1. Adults unable to give informed consent due to cognitive impairment or mental disorders. 2. Children below the age of consent 3. Pregnant women 4. Prisoners 5. History of chronic disorders like hypertension, diabetes, hyperlipidemia, depression, hypothyroidism etc. that require chronic treatment 6. Known chronic fatigue syndrome 7. Blood disorders or coagulopathy 8. Chronic allergies or history of asthma. 9. Using antihistamines, bronchodilators or H2 blockers for hyperacidity 10. Using medications for sleep, or known sleep disorders 11. Any medication or condition deemed unsuitable by the PI Exclusion Criteria for Patients with Multiple Sclerosis (MS): 1. Adults unable to give informed consent due to cognitive impairment or mental disorders. 2. Children below the age of consent 3. Pregnant women 4. Prisoners 5. Systemic disorders known to cause fatigue such as severe anemia, infections, chronic systemic infectious or inflammatory disorders, including known autoimmune disorders. 6. Chronic fatigue syndrome 7. Hypothyroidism 8. Systemic malignancy 9. Undergoing chemotherapy 10. Depression 11. Sleep disorders including narcolepsy, excessive day-time sleep. 12. History of substance abuse 13. Excessive consumption of coffee or over-the-counter stimulants 14. Concomitant medications of amantadine, methylphenidate, amphetamines, pemoline, barbiturates, tizanidine, Monoamine oxidase inhibitor (MAO) inhibitors, benzodiazepines, barbiturates, tricyclic antidepressants, antihistamines, H2 blockers for gastro-esophageal reflux disease (GERD), selective serotonin reuptake inhibitors (SSRIs) and any other medication that in the opinion of the PI should be excluded. 15. Patients who were using modafinil for treatment of fatigues prior to the study may participate but will be required to undergo a washout of 2 weeks prior to entry into the trial.