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The antinociceptive effect of narcotic and non-narcotic analgesics is dependent, in part, on central mechanisms mediated by serotonin (5-HT). Shorter-term exposure to paracetamol (acetaminophen) increases levels of 5-HT in the cerebral cortex, pons, and platelets. Longer-term exposure to analgesics, especially in migraine suffers, may, paradoxically, worsen and perpetuate headache. A reduction in platelet 5-HT has been observed in such patients, and when analgesics are withdrawn, an increase in the platelet 5-HT-level and improvement in the headaches. These authors investigated the effect of paracetamol on various 5-HT-related CNS parameters in an animal model.
After shorter-term (15 days) or longer-term (30 days) administration of paracetam…