Spinal GABA A and GABA B receptor pharmacology in a rat model of neuropathic pain

T. Philip Malan, Heriberto P. Mata, Frank Porreca

Research output: Contribution to journalArticle

208 Citations (Scopus)

Abstract

Background: This study tests the hypothesis that loss of spinal activity of γ-aminobutyric acid (GABA) contributes to the allodynia and hyperalgesia observed after peripheral nerve injury. Methods: Intrathecal catheters were implanted in male Sprague-Dawley rats. Antinociception was assessed by measuring withdrawal latency to immersion of the tail in a 52°C water bath. Nerve injury was produced by ligation of the L5 and L6 spinal nerves. Testing was performed 4-14 days after spinal nerve ligation, when tactile allodynia and thermal hyperalgesia were established. Tactile allodynia was quantitated using the threshold to withdrawal of the hind paw on probing with von Frey filaments. Thermal hyperalgesia was quantitated using the latency to withdrawal of the hind paw from radiant heat. Motor function was tested using a rotarod apparatus. Results: Spinal administration of the GABA A receptor antagonist bicuculline or the GABA B receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia in normal rats. The GABA B receptor agonist baclofen, administered spinally, produced antinociception in the tail-flick test, whereas the GABA A receptor agonist isoguvacine did not. Isoguvacine and baclofen each reversed tactile allodynia and thermal hyperalgesia produced by spinal nerve ligation. Baclofen but not isoguvacine prolonged thermal withdrawal latency in nerve-injured rats beyond preoperative values. Baclofen but not isoguvacine impaired motor function. Conclusions: Pharmacologic inhibition of intrinsic GABA tone in normal rats resulted in tactile allodynia and thermal hyperalgesia, consistent with the hypothesis being tested. Exogenous administration of GABA agonists reversed spinal nerve ligation-induced allodynia and hyperalgesia, also consistent with this hypothesis. Isoguvacine produced specific antihyperalgesic and antiallodynic effects, whereas assessment of the effects of baclofen was complicated by motor dysfunction. Spinal GABA A agonists may provide a specific therapy for neuropathic pain.

Original languageEnglish (US)
Pages (from-to)1161-1167
Number of pages7
JournalAnesthesiology
Volume96
Issue number5
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

GABA-B Receptors
Hyperalgesia
Neuralgia
gamma-Aminobutyric Acid
Pharmacology
Baclofen
Spinal Nerves
Ligation
GABA-A Receptor Agonists
Tail
Hot Temperature
GABA-B Receptor Antagonists
GABA-B Receptor Agonists
GABA Agonists
Aminobutyrates
GABA-A Receptor Antagonists
Peripheral Nerve Injuries

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Spinal GABA A and GABA B receptor pharmacology in a rat model of neuropathic pain. / Malan, T. Philip; Mata, Heriberto P.; Porreca, Frank.

In: Anesthesiology, Vol. 96, No. 5, 2002, p. 1161-1167.

Research output: Contribution to journalArticle

Malan, T. Philip ; Mata, Heriberto P. ; Porreca, Frank. / Spinal GABA A and GABA B receptor pharmacology in a rat model of neuropathic pain. In: Anesthesiology. 2002 ; Vol. 96, No. 5. pp. 1161-1167.
@article{d6bb444b89314966a2769ab1c081c624,
title = "Spinal GABA A and GABA B receptor pharmacology in a rat model of neuropathic pain",
abstract = "Background: This study tests the hypothesis that loss of spinal activity of γ-aminobutyric acid (GABA) contributes to the allodynia and hyperalgesia observed after peripheral nerve injury. Methods: Intrathecal catheters were implanted in male Sprague-Dawley rats. Antinociception was assessed by measuring withdrawal latency to immersion of the tail in a 52°C water bath. Nerve injury was produced by ligation of the L5 and L6 spinal nerves. Testing was performed 4-14 days after spinal nerve ligation, when tactile allodynia and thermal hyperalgesia were established. Tactile allodynia was quantitated using the threshold to withdrawal of the hind paw on probing with von Frey filaments. Thermal hyperalgesia was quantitated using the latency to withdrawal of the hind paw from radiant heat. Motor function was tested using a rotarod apparatus. Results: Spinal administration of the GABA A receptor antagonist bicuculline or the GABA B receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia in normal rats. The GABA B receptor agonist baclofen, administered spinally, produced antinociception in the tail-flick test, whereas the GABA A receptor agonist isoguvacine did not. Isoguvacine and baclofen each reversed tactile allodynia and thermal hyperalgesia produced by spinal nerve ligation. Baclofen but not isoguvacine prolonged thermal withdrawal latency in nerve-injured rats beyond preoperative values. Baclofen but not isoguvacine impaired motor function. Conclusions: Pharmacologic inhibition of intrinsic GABA tone in normal rats resulted in tactile allodynia and thermal hyperalgesia, consistent with the hypothesis being tested. Exogenous administration of GABA agonists reversed spinal nerve ligation-induced allodynia and hyperalgesia, also consistent with this hypothesis. Isoguvacine produced specific antihyperalgesic and antiallodynic effects, whereas assessment of the effects of baclofen was complicated by motor dysfunction. Spinal GABA A agonists may provide a specific therapy for neuropathic pain.",
author = "Malan, {T. Philip} and Mata, {Heriberto P.} and Frank Porreca",
year = "2002",
doi = "10.1097/00000542-200205000-00020",
language = "English (US)",
volume = "96",
pages = "1161--1167",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Spinal GABA A and GABA B receptor pharmacology in a rat model of neuropathic pain

AU - Malan, T. Philip

AU - Mata, Heriberto P.

AU - Porreca, Frank

PY - 2002

Y1 - 2002

N2 - Background: This study tests the hypothesis that loss of spinal activity of γ-aminobutyric acid (GABA) contributes to the allodynia and hyperalgesia observed after peripheral nerve injury. Methods: Intrathecal catheters were implanted in male Sprague-Dawley rats. Antinociception was assessed by measuring withdrawal latency to immersion of the tail in a 52°C water bath. Nerve injury was produced by ligation of the L5 and L6 spinal nerves. Testing was performed 4-14 days after spinal nerve ligation, when tactile allodynia and thermal hyperalgesia were established. Tactile allodynia was quantitated using the threshold to withdrawal of the hind paw on probing with von Frey filaments. Thermal hyperalgesia was quantitated using the latency to withdrawal of the hind paw from radiant heat. Motor function was tested using a rotarod apparatus. Results: Spinal administration of the GABA A receptor antagonist bicuculline or the GABA B receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia in normal rats. The GABA B receptor agonist baclofen, administered spinally, produced antinociception in the tail-flick test, whereas the GABA A receptor agonist isoguvacine did not. Isoguvacine and baclofen each reversed tactile allodynia and thermal hyperalgesia produced by spinal nerve ligation. Baclofen but not isoguvacine prolonged thermal withdrawal latency in nerve-injured rats beyond preoperative values. Baclofen but not isoguvacine impaired motor function. Conclusions: Pharmacologic inhibition of intrinsic GABA tone in normal rats resulted in tactile allodynia and thermal hyperalgesia, consistent with the hypothesis being tested. Exogenous administration of GABA agonists reversed spinal nerve ligation-induced allodynia and hyperalgesia, also consistent with this hypothesis. Isoguvacine produced specific antihyperalgesic and antiallodynic effects, whereas assessment of the effects of baclofen was complicated by motor dysfunction. Spinal GABA A agonists may provide a specific therapy for neuropathic pain.

AB - Background: This study tests the hypothesis that loss of spinal activity of γ-aminobutyric acid (GABA) contributes to the allodynia and hyperalgesia observed after peripheral nerve injury. Methods: Intrathecal catheters were implanted in male Sprague-Dawley rats. Antinociception was assessed by measuring withdrawal latency to immersion of the tail in a 52°C water bath. Nerve injury was produced by ligation of the L5 and L6 spinal nerves. Testing was performed 4-14 days after spinal nerve ligation, when tactile allodynia and thermal hyperalgesia were established. Tactile allodynia was quantitated using the threshold to withdrawal of the hind paw on probing with von Frey filaments. Thermal hyperalgesia was quantitated using the latency to withdrawal of the hind paw from radiant heat. Motor function was tested using a rotarod apparatus. Results: Spinal administration of the GABA A receptor antagonist bicuculline or the GABA B receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia in normal rats. The GABA B receptor agonist baclofen, administered spinally, produced antinociception in the tail-flick test, whereas the GABA A receptor agonist isoguvacine did not. Isoguvacine and baclofen each reversed tactile allodynia and thermal hyperalgesia produced by spinal nerve ligation. Baclofen but not isoguvacine prolonged thermal withdrawal latency in nerve-injured rats beyond preoperative values. Baclofen but not isoguvacine impaired motor function. Conclusions: Pharmacologic inhibition of intrinsic GABA tone in normal rats resulted in tactile allodynia and thermal hyperalgesia, consistent with the hypothesis being tested. Exogenous administration of GABA agonists reversed spinal nerve ligation-induced allodynia and hyperalgesia, also consistent with this hypothesis. Isoguvacine produced specific antihyperalgesic and antiallodynic effects, whereas assessment of the effects of baclofen was complicated by motor dysfunction. Spinal GABA A agonists may provide a specific therapy for neuropathic pain.

UR - http://www.scopus.com/inward/record.url?scp=0036237512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036237512&partnerID=8YFLogxK

U2 - 10.1097/00000542-200205000-00020

DO - 10.1097/00000542-200205000-00020

M3 - Article

C2 - 11981157

AN - SCOPUS:0036237512

VL - 96

SP - 1161

EP - 1167

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 5

ER -