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Preparation of Acute Spinal Cord Slices for Whole-cell Patch-clamp Recording in Substantia Gelatinosa Neurons
Published on: January 18, 2019
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Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.
Yung-Jen Huang1, Kuan H Lee2, Lauren Murphy1
1Behavioral and Cellular Neuroscience, Department of Psychology, Texas A&M University, College Station, TX 77843, USA.
Experimental Neurology
|September 19, 2016
Summary
Spinal cord injury transforms GABA from an inhibitor to an exciter in pain pathways. This shift, driven by reduced chloride transport, promotes chronic pain by enhancing nociceptive sensitization.
Area of Science:
- Neuroscience
- Pain Research
- Spinal Cord Injury
Background:
- Noxious stimuli can sensitize spinal pain circuits, leading to central sensitization and chronic pain.
- Descending fibers and GABAergic interneurons regulate spinally-mediated central sensitization.
- GABA typically inhibits nociceptive transmission in the adult spinal cord.
Purpose of the Study:
- To investigate how spinal cord injury (SCI) alters GABAergic function in nociceptive transmission.
- To determine the role of GABA in the development of nociceptive sensitization after SCI.
- To explore the underlying mechanisms, including chloride transport, involved in SCI-induced changes in GABA function.
Main Methods:
- Spinally transected and sham-operated rats were used to model SCI.
- Noxious electrical stimulation, inflammation, and capsaicin were used to induce nociceptive sensitization.
- Behavioral (enhanced mechanical reactivity) and cellular (c-fos, pERK) indices were measured.
- Pharmacological agents targeting GABA receptors (bicuculline, muscimol), KCC2 transporters (DIOA), and chloride levels (bumetanide) were administered.
Main Results:
- SCI induced nociceptive sensitization (EMR) that was blocked by a GABAA receptor antagonist (bicuculline).
- In intact rats, bicuculline exacerbated sensitization, while a GABA agonist (muscimol) attenuated it.
- SCI reduced KCC2 transporter expression, leading to decreased intracellular chloride and a shift towards GABAergic excitation.
- Blocking KCC2 mimicked SCI effects, while increasing intracellular chloride with bumetanide reversed SCI-induced sensitization.
Conclusions:
- Spinal cord injury reverses the inhibitory role of GABA in nociceptive transmission, making it excitatory.
- This GABAergic excitation, driven by reduced KCC2-mediated chloride transport, contributes to central sensitization and chronic pain.
- Targeting chloride homeostasis presents a potential therapeutic strategy for managing pain after spinal cord injury.
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