Date of Award

Spring 2019

Document Type

Honors Thesis


Basic Biomedical Science

First Advisor

Dr. Brian Burrell

Second Advisor

Dr. Kenneth Renner

Third Advisor

Dr. Andrea Liebl


serotonin, pain, nociception, endocannabinoid, stress


Stress-induced analgesia is characterized by a reduction in response to painful stimuli. However, a sufficiently stressful stimulus may exhibit a pro-nociceptive effect in addition to its anti-nociceptive effect. Previous studies suggest that endocannabinoids reduce responses to nociceptive stimuli and may contribute to stress-induced analgesia. However, endocannabinoids can also have pro-nociceptive effects by increasing responses to non-nociceptive stimuli. In this study, I hypothesized that stressful stimuli could produce both pro- and anti-nociceptive effects and that these effects were endocannabinoid-mediated. In these experiments, the medicinal leech (Hirudo verbana) was shocked twice per minute for 15 minutes. Response to nociceptive stimuli was measured using a Hargreaves Apparatus to test latency to thermal nociceptive stimuli. The non-nociceptive response was measured by Von Frey fibers which test response to mechanical stimulation. The electric shocks did not alter responses to the nociceptive stimulus but did cause sensitization to the non-nociceptive stimulus. These experiments were repeated with drugs that blocked either endocannabinoid synthesis or the endocannabinoid receptor. Neither treatment had any effect on the responses to either stimulus. The electrical stimulus reliably raised 5HT levels in the CNS, suggesting a stressed-state. Injections of 5HT were used to mimic the electric stimulus and a 5HT receptor antagonist, methysergide, was used to block this effect. Injections of 5HT caused sensitization to the non-nociceptive stimulus and the response was concentration dependent. The 5HT injection had no effect on the nociceptive stimulus. Injections of methysergide reduced sensitization to non-nociceptive stimuli after electric stimulations. The lack of change in response to the nociceptive stimulus may indicate a need to alter the pattern of electric stimulation.



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