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Is Acute Tolerance to 5-Hydroxytryptamine Opioid Dependent? Its Absence in Migraine Sufferers

The human dorsal hand vein, exhausted in vivo (tachyphylaxis) by repeated inoculations of 5-hydroxytryptamine, recovers its capacity to contract in response to the 5HT when naloxone (per se ineffective) is inoculated into the same vein. It would seem, therefore, that in the 5HT tachyphylactic mechanism a role could be played by the progressive excitation of a local opioid modulator apparatus (silent in basal condition); naloxone's capacity for neutralizing the vein's fatigue could be indirect evidence of this. This postulation of an opioid role in the tachyphylactic mechanism differs from the conventional thesis, which explains tachyphylaxis as a progressive exhaustion of NA released from the sympathetic neuron by 5HT (see Table 1). Tachyphylaxis is poor, delayed or absent in migraine sufferers; this anomaly is present even in the period between attacks. The anomaly of inverted tachyphylaxis appears amplified during attacks. The loss or inversion of 5HT-tachyphylaxis is constantly observed in heroin addicts during acute abstinence. The fact that the clinical phenomena of acute heroin abstinence are comparable with those of a migraine attack could be a matter for further investigation.