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Mutations affecting glycinergic neurotransmission in hyperekplexia increase pain sensitivity
Pascal Henri Vuilleumier1, Raphael Fritsche2, Jürg Schliessbach1
1Department of Anaesthesiology and Pain Medicine, Bern University Hospital, University of Bern, Switzerland.
Brain : a Journal of Neurology
|November 18, 2017
Summary
Patients with hyperekplexia, a rare neurological disorder, exhibit heightened pain sensitivity and impaired pain modulation. This suggests glycine receptors are crucial for regulating pain perception in humans.
Area of Science:
- Neuroscience
- Pain Research
- Genetics
Background:
- Spinal cord inhibitory interneurons utilize glycine and GABA for fast neurotransmission.
- Research on these inhibitory pain pathways is abundant in animal models but limited in humans.
- Hyperekplexia is a rare human disorder linked to loss-of-function mutations in glycine receptors and transporters.
Purpose of the Study:
- To investigate whether hyperekplexia patients have altered pain perception or central pain modulation compared to healthy individuals.
- To explore the role of glycinergic neurotransmission in human pain processing.
Main Methods:
- Compared seven hyperekplexia patients with 14 healthy controls.
- Utilized quantitative sensory tests including pressure pain threshold, ice water tolerance, electrical pain thresholds, nociceptive withdrawal reflex, and conditioned pain modulation.
- Analyzed data using linear mixed models.
Main Results:
- Hyperekplexia patients showed significantly lower pain thresholds across all tested quantitative sensory tests.
- Specifically, pressure pain detection threshold, ice water tolerance, and electrical pain detection thresholds were reduced in patients.
- Conditioned pain modulation was also significantly impaired in hyperekplexia patients.
Conclusions:
- Hyperekplexia is associated with increased pain sensitivity in humans.
- The study supports the critical role of glycinergic neurotransmission in human central pain modulation.
- Findings highlight the importance of glycine receptors in regulating pain perception.
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