Abstract
The mechanisms facilitating or prompting the chronicization of headache and the increased use of analgesics are still unknown and under debate. It is not clear whether the daily use of analgesics in chronic headaches is to be considered a habit or a therapeutic need. Recently, our group showed that items more involved in chronicization of headaches were the onset as migraine and the use of analgesics, namely mixture compounds. One of the most important features in inducing habit behavior is the reward: in this illness, does the reward come from the pain relief or from the intrinsic euphoric activity of the drugs, or does it depend on a more complex behavior? Although the system of neurotransmitters involved in the biology of reward is complex, at least four neurotransmitters are known to be involved at several sites in the brain: serotonin in the hypothalamus, the enkephalins (opioid peptides) in the ventral tegmental area, DOPA in nucleus accumbens, and the inhibitory neurotransmitter GABA in the ventral tegmental area and the nucleus accumbens. In a normal person, these neurotransmitters work together in a cascade of excitation or inhibition between complex stimuli and complex responses leading to a feeling of well being, the ultimate reward. In the cascade theory of reward, a disruption of these intercellular interactions results in anxiety, anger and other “bad feelings” or in a craving for a substance that alleviates these negative emotions. Probably, serotonin plays a pivotal role in migrane pathogenesis, thus drugs alleviating migraine should act through this neurotransmitter. Therefore, these drugs when used in specific settings, as compulsive behavior, may contribute to the development of mechanisms of reward linked to its use and may induce habit behavior. Epidemiological studies support this idea. The chronic use of barbiturate- or opiatecontaining analgesics is preferred by patients who daily consume drugs and who suffer from daily headaches.
Highlights
The treatment of headache patients is often complicated by substance abuse that may progress to a drug dependency
An alteration in serotonin concentration has been found in patients with chronic daily headache (CDH) linked with abuse of analgesic drugs, as has been the up-regulation of 5HT2 platelet receptors, which has been correlated with chronicization of headache [1]
The main problem with the role of daily analgesic use in the maintenance of chronic headache depends on the lack of animal models in which to evaluate the relationship between drug use and headache
Summary
The treatment of headache patients is often complicated by substance abuse that may progress to a drug dependency. Patients with analgesic-induced headaches have lower basal content of platelet 5HT; their platelets exhibit reduced 5HT uptake when incubated with excess of the amine, and have a greater density of 5HT2receptors on the plasma membrane than migrainous patients without analgesic-reduced headache [1]. These observations suggest that chronic analgesic overuse interferes with the intrinsic pain modulatory system by depletion of 5HT and by up-regulation of its post-synaptic receptors. The constancy in preference for mixtures, both barbiturate and percholperazine-containing compounds, suggests an addictive effect of small doses of these central-acting drugs in maintaining daily drug use. We outline in this paper the linkage between the serotonergic system in the brain and its potential role in reward mechanisms
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