Intraspinal transplantation of GABAergic neural progenitors attenuates neuropathic pain in rats: A pharmacologic and neurophysiological evaluation

Stanislava Jergova, Ian Hentall, Shyam Gajavelli, Mathew S. Varghese, Jacqueline Sagen

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Dysfunctional γ-aminobutyric acid (GABA)-ergic inhibitory neurotransmission is hypothesized to underlie chronic neuropathic pain. Intraspinal transplantation of GABAergic neural progenitor cells (NPCs) may reduce neuropathic pain by restoring dorsal horn inhibition. Rat NPCs pre-differentiated to a GABAergic phenotype were transplanted into the dorsal horn of rats with unilateral chronic constriction injury (CCI) of the sciatic nerve. GABA signaling in antinociceptive effects of NPC grafts was tested with the GABA A receptor antagonist bicuculline (BIC), GABA B receptor antagonist CGP35348 (CGP) and GABA reuptake inhibitor SKF 89976A (SKF). NPC-treated animals showed decreased hyperalgesia and allodynia 1-3week post-transplantation; vehicle-injected CCI rats continued displaying pain behaviors. Intrathecal application of BIC or CGP attenuated the antinociceptive effects of the NPC transplants while SKF injection induced analgesia in control rats. Electrophysiological recordings in NPC treated rats showed reduced responses of wide dynamic range (WDR) neurons to peripheral stimulation compared to controls. A spinal application of BIC or CGP increased wind-up response and post-discharges of WDR neurons in NPC treated animals. Results suggest that transplantation of GABAergic NPCs attenuate pain behaviors and reduce exaggerated dorsal horn neuronal firing induced by CCI. The effects of GABA receptor inhibitors suggest participation of continuously released GABA in the grafted animals.

Original languageEnglish
Pages (from-to)39-49
Number of pages11
JournalExperimental Neurology
Volume234
Issue number1
DOIs
StatePublished - Mar 1 2012

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Neuralgia
Stem Cells
Transplantation
Bicuculline
Constriction
gamma-Aminobutyric Acid
Hyperalgesia
Wounds and Injuries
GABA Uptake Inhibitors
GABA-B Receptor Antagonists
Aminobutyrates
Transplants
GABA-A Receptor Antagonists
Neurons
Pain
GABA Receptors
Sciatic Nerve
Synaptic Transmission
Chronic Pain
Analgesia

Keywords

  • GABA receptors
  • GABAergic progenitors
  • Neuropathic pain
  • Post-discharges
  • Wind-up

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Intraspinal transplantation of GABAergic neural progenitors attenuates neuropathic pain in rats : A pharmacologic and neurophysiological evaluation. / Jergova, Stanislava; Hentall, Ian; Gajavelli, Shyam; Varghese, Mathew S.; Sagen, Jacqueline.

In: Experimental Neurology, Vol. 234, No. 1, 01.03.2012, p. 39-49.

Research output: Contribution to journalArticle

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