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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
Increased nociceptive input rapidly modulates spinal GABAergic transmission through endogenously released glutamate
Hong-Yi Zhou1, Hong-Mei Zhang, Shao-Rui Chen
1Department of Anesthesiology and Pain Medicine, Unit 409, The University of Texas M. D. Anderson Cancer Center, 1400 Holcombe Blvd., Houston, TX 77030, USA.
Journal of Neurophysiology
|November 17, 2006
Summary
Stimulating pain pathways rapidly reduces inhibitory signals in the spinal cord. This involves glutamate and specific receptors, impacting pain processing in the dorsal horn.
Area of Science:
- Neuroscience
- Pain Research
- Spinal Cord Physiology
Background:
- Nociceptive primary afferents transmit pain signals via glutamatergic transmission.
- The regulation of GABAergic tone in the spinal dorsal horn by nociceptive input is poorly understood.
Purpose of the Study:
- To investigate how increased nociceptive input affects GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) in lamina II neurons.
- To elucidate the mechanisms underlying the modulation of GABAergic tone during nociception.
Main Methods:
- Whole-cell recordings in rat spinal cord slices.
- Application of capsaicin to stimulate nociceptive afferents.
- Pharmacological manipulation using pertussis toxin, ionotropic glutamate receptor antagonists, and metabotropic glutamate receptor antagonists (LY341495, CPPG).
Main Results:
- Capsaicin induced long-lasting inhibition of sIPSCs in 50% of lamina II neurons.
- This inhibition was dependent on G-protein signaling and endogenous glutamate release.
- The effect was mediated by presynaptic group II and group III metabotropic glutamate receptors.
- Bradykinin also inhibited sIPSCs, an effect abolished by metabotropic glutamate receptor antagonists.
Conclusions:
- Stimulation of nociceptive primary afferents rapidly suppresses GABAergic input to dorsal horn neurons.
- This suppression occurs via endogenous glutamate acting on presynaptic metabotropic glutamate receptors.
- These findings reveal a novel mechanism in spinal cord microcircuitry regulating nociception.
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