Serotonin: Pleasure or Pain?

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Dr. Mark Siddall

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1836 Serotonin: Pleasure or Pain?
Megan Gavin

Psychedelic philosopher Alan Watts may have been right when he wrote that we “cannot be more sensitive to pleasure without being more sensitive to pain.”  Prescriptions for SSRIs and MAOIs increased more than 400% over a 20 year interval, all with the aim of boosting serotonin levels to promote happiness and reduce anxiety. Yet millions of years of evolution have witnessed a menagerie of venomous animals independently leveraging serotonin for a contradictory effect: the infliction of excruciating pain. 

Ninety percent of our serotonin keeps the gastrointestinal system running properly.  In the central nervous system, serotonin is responsible for mediating a wide range of feelings including pleasure, contentedness and even appetite and sleep. Antidepressants work by extend the life of serotonin either by blocking enzymes that normally clear it from circulation (MAOIs) or by preventing its reuptake from synapses in the brain (SSRIs).  The result is usually a dramatic improvement in one’s sense of well-being. 


It’s ironic that an agent of such happiness is equally responsible for so much misery.  Subcutaneous injection of even minuscule quantities of serotonin will cause pain sensing neurons called nociceptors to fire wildly.  The resulting dump of prostaglandins, bradykinin and substance P results in a state of hyperalgesia; Greek for “above pain.”

No wonder then that so many animals have deployed serotonin in their own defense.  The searing pain of a hornet sting is caused in large part by the presence of serotonin in its complex venomous cocktail.  So too is the agony inflicted by some sea urchin stings. 

Amazingly, the deployment of serotonin in the chemical arsenal of venom cuts a wide swath across invertebrates and even some vertebrates detailed in a new book “Poison: Sinister Species with Deadly Consequences” by Dr. Mark Siddall of the American Museum of Natural History in New York city.  

The deathstalker scorpion (Leiurus quinquestriatus) ranges from North Africa to Pakistan.  in addition to serotonin, the deathstalker’s venom includes a lethal mix of agitoxins, charybdotoxin, chlorotoxin, and scyllatoxin. 


Species of Phoenuetria, including the wandering spiders and banana spiders are feared for their aggressive behaviour. And rightly-so.  A huge dose of serotonin allows them to inflict some of the most painful spider bites.  Another venom compound, PhTx3, can result in painful priapism.   

A lot of the lasting damage caused by the venom-soaked foot-long serrated barb of a blue spotted stingray (Neotrygon kuhlii) is due to flesh liquefying enzymes combined with some serotonin just to make sure it’s painful.  

The tenacious bites of Gila monsters (Heloderma suspectum) squeeze venom along grooved lower teeth - which is made only more painful by the presence of serotonin.   Other venom components include hypothermia inducing helothermine, and exendin-4 a synthetic version of which is now a blockbuster drug for controlling type-2 diabetes. 

The flashing iridescent patterns on each of three species of Hapalochlaena belie a dangerous beauty.  A blue-ringed octopus bite comprises a dizzying neuroactive cocktail of serotonin, tryptamine, octopamine, tyramine, and acetylcholine along with a deadly dose of tetrodotoxin.


Curator and Professor at the American Museum of Natural History, Siddall recently curated the “Power of Poison" exhibition, which will be traveling internationally for the coming years.  He is is now busy working on two new exhibitions for the spring of 2015: one celebrating animal super powers and another in collaboration with the Carter Center that explores the prospects for global disease eradication. You can buy his new book, “Poison: Sinister Species with Deadly Consequences" here.

All images by Megan Gavin, used with permission.


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