Title:
Identifying the potential effect of zolmitriptan on the 1b pathway of Golgi tendon organs in regulating intermuscular inhibition in the extremities to find a link in the mechanism of spasticity

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Davis, Adam Eugene
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Nichols, T. Richard
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Abstract
The deep dorsal horn (DDH) of the spinal cord is a major integration center for receiving a variety of neural projections from the brainstem as well as a variety of afferent inputs from muscle spindles and Golgi tendon organs (GTOs) in the muscles. Following spinal cord injury (SCI) to the DDH, an overall loss of serotonergic input from the brainstem is observed, for which there is evidence to suggest that this may play a role in inhibiting the activity of bursting interneurons in the DDH, possibly leading to uncontrolled motoneuron activity, hyperreflexia. GTOs primarily supply the force feedback network (FBB), which also receives supraspinal input through the DDH, likely also affected by its loss in SCI. The purpose of this current study is to investigate if FBB function changes, with or without SCI, after the administration of a specific serotonin reuptake inhibitor (SSRI), zolmitriptan, which inhibits the activity of the bursting interneurons. FBB function was determined primarily as inhibitory signals from the flexor hallucis longus (FHL) onto the gastrocnemius (GAS), the muscle tensions compared after being stretched individually and pairwise, with some data from rectus femoris (RF) onto GAS. The autogenic stretch reflex was analyzed only in GAS. Animals with an intact spinal cord (n=1) and with a lateral hemisection (n=2) were used to compare the changes in reflexes following zolmitriptan administration. Data was variable across the subjects with no clear effect on the autogenic stretch reflex in GAS. The more stable lateral hemisection subject revealed that zolmitriptan largely and consistently increased inhibition from FHL onto GAS from a miniscule baseline, suggesting connectivity between the GTO circuit and the bursting interneurons of the DDH. Notably in the intact spinal cord animal, there was an immediate and complete correction of oscillations in the baseline tension of all muscles after drug administration, treating a symptom of hyperreflexia. These results suggest a connection between the two systems or a more significant role of this particular serotonin receptor on GTO circuit and the DDH. More studies may provide a deeper understanding of this network and these findings.
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Date Issued
2023-01-18
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Undergraduate Thesis
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