American Society of Hirudotherapy

Serotonin mediates stress-like effects on responses to non-nociceptive stimuli in the medicinal leech Hirudo verbana

Basic science published in J Exp Biol (2022)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Preclinical (animal)Genomics & ProteomicsMack D et al. · The Journal of experimental biology, 2022

Abstract

Noxious stimuli can elicit stress in animals that produce a variety of adaptations including changes in responses to nociceptive and non-nociceptive sensory input. One example is stress-induced analgesia that may be mediated, in part, by the endocannabinoid system. However, endocannabinoids can also have pro-nociceptive effects. In this study, the effects of electroshock, one experimental approach for producing acute stress, were examined on responses to non-nociceptive mechanical stimuli and nociceptive thermal stimuli in the medicinal leech (Hirudo verbana). The electroshock stimuli did not alter the leeches' responses to nociceptive stimuli, but did cause sensitization to non-nociceptive stimuli, characterized by a reduction in response threshold. These experiments were repeated with drugs that either blocked synthesis of the endocannabinoid transmitter 2-arachidonoylglycerol (2-AG) or transient receptor potential vanilloid (TRPV) channel, which is known to act as an endocannabinoid receptor. Surprisingly, neither treatment had any effect on responses following electroshock. However, the electroshock stimuli reliably increased serotonin (5-hydroxytryptamine or 5HT) levels in the H. verbana CNS. Injection of 5HT mimicked the effects of the electroshocks, sensitizing responses to non-nociceptive stimuli and having no effect on responses to nociceptive stimuli. Injections of the 5HT receptor antagonist methysergide reduced the sensitization effect to non-nociceptive stimuli after electroshock treatment. These results indicate that electroshocks enhance response to non-nociceptive stimuli but do not alter responses to nociceptive stimuli. Furthermore, while 5HT appears to play a critical role in this shock-induced sensitizing effect, the endocannabinoid system seems to have no effect.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, N.I.H., Extramural
Indexed MeSH termsAnimalsEndocannabinoidsHirudo medicinalisLeechesSerotonin

Summary

Electroshock stress in Hirudo verbana elevates CNS serotonin and sensitizes non-nociceptive responses without affecting nociceptive responses. 5HT antagonist methysergide blocks the sensitization.

Why This Matters for Hirudotherapy

This study examined whether electroshock-induced stress in Hirudo verbana alters responses to nociceptive thermal and non-nociceptive mechanical stimuli, finding that electroshock sensitized responses to non-nociceptive stimuli (reduced threshold) without affecting nociceptive responses. Surprisingly, blockade of endocannabinoid synthesis (2-AG) or TRPV channels had no effect, but serotonin (5HT) levels increased in the leech CNS after electroshock; 5HT injection mimicked the sensitization, and the 5HT receptor antagonist methysergide reduced it. This work is relevant to ASH's domain as it uses the medicinal leech as a model organism to study neuromodulatory mechanisms underlying sensory processing and stress-related sensitization. The study is purely basic neuroscience and does not address hirudotherapy, the leech secretome, or any therapeutic application.

Citation

Serotonin mediates stress-like effects on responses to non-nociceptive stimuli in the medicinal leech Hirudo verbana.

Mack D et al. · The Journal of experimental biology, 2022

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

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