When the usual regular dose of caffeine is delayed, the caffeine remaining in the body is catabolized (dismantled and thereby deactivated) by enzymes in the liver. With caffeine gone, formerly blocked adenosine can access, bind to, occupy, and activate now unblocked and excessively numerous adenosine receptors. With too many adenosine molecules attached too long to too many adenosine receptors, the nervous system malfunctions.
Excessive adenosine, combined with excessive sensitivity to adenosine, generates the pain of caffeine withdrawal headache and likely causes migraine head pain as well. In a person abnormally insensitive to excitatory neurotransmitter chemicals inhibited by adenosine, excessive adenosine receptor activation causes a shortfall in excitatory neurotransmitter receptor activation. As a result, systems controlled by those neurotransmitters malfunction, and those malfunctions generate migraine symptoms. A shortage of serotonin receptor activation prevents serotonin from appropriately blocking pain. A shortage of acetylcholine, a neurotransmitter essential to vision, in the retinas may cause the visual disturbances associated with migraine. A shortage of dopamine may cause the emotional and behavioral effects associated with migraine. And a shortage of norepinephrine, the final neurotransmitter of the sympathetic nervous system, causes the symptoms of sympathetic hypofunction (inadequate functioning of the sympathetic nervous system) associated with primary headache.
RESULTS AND CONCLUSION:
We have reached a dual conclusion: 1) during migraine headaches there is an increase (mean 68%) in circulating adenosine levels and this increase may participate in cephalalgia; 2) activation of A2 receptors by adenosine causes a dose-dependent serotonin uptake by platelets. This inhibition of uptake could participate in the rapid elimination of serotonin in migraine sufferers. As a result of this, the use of adenosine antagonists could be an effective complementary treatment for migraine.
Guieu R, Devaux C, Henry H, Bechis G, Pouget J, Mallet D, Sampieri F, Juin M, Gola R, Rochat H. Adenosine and migraine. Can J Neurol Sci. 1998 Feb;25(1):55-8. Abstract
Cerebrospinal fluid analyses in migraine patients and controls.
Rothrock JF, Mar KR, Yaksh TL, Golbeck A, Moore AC.
San Diego (UCSD) Headache Center, University of California, USA.
To investigate the role of central neurotransmitters in the pathogenesis of migraine, we measured cerebrospinal fluid (CSF) levels of certain amino acids (glycine, taurine, glutamine) and metabolites of biogenic amines (5-hydroxyindoleacetic acid and homovanillic acid) in 38 migraine patients and compared them with the levels from 10 headache-free controls. The levels of taurine, glycine and glutamine were significantly higher in the migraine patients (p < 0.0001 for taurine and glycine; p < 0.0009 for glutamine); there were no significant differences among the three migraine subgroups (infrequent migraine, frequent migraine and transformed migraine). In seven patients subsequently treated with divalproex sodium, CSF taurine levels decreased significantly from pretreatment baseline values. These data support the concept that migraine is at least in part a disorder of central neurotransmission.
Coffee, a major source of caffeine, is also a major source of niacin, a necessary nutrient, and coffee also contains antioxidants. Coffee drinking is associated with a lower risk of type 2 diabetes,44 and protects against cardiovascular disease.45 Green tea protects against various cancers.