Korean J Pain.  2006 Jun;19(1):22-32. 10.3344/kjp.2006.19.1.22.

Spinal and Peripheral GABA-A and B Receptor Agonists for the Alleviation of Mechanical Hypersensitivity following Compressive Nerve Injury in the Rat

• Jeon YH
• Yoon DM
• Nam TS
• Leem JW
• Paik GS

• KMID: 2278012
• DOI: http://doi.org/10.3344/kjp.2006.19.1.22

Abstract

BACKGROUND: This study was conducted to investigate the roles of the spinal and peripheral gamma-aminobutyric acid (GABA)-ergic systems for the mechanical hypersensitivity produced by chronic compression of the dorsal root ganglion (CCD).
METHODS
CCD was performed at the left 5th lumbar dorsal root ganglion. The paw withdrawal threshold (PWT) to von Frey stimuli was measured. The mechanical responsiveness of the lumbar dorsal horn neurons was examined. GABAergic drugs were delivered with intrathecal (i.t.) or intraplantar (i.pl.) injection or by topical application onto the spinal cord.
RESULTS
CCD produced mechanical hypersensitivity, which was evidenced by the decrease of the PWT, and it lasting for 10 weeks. For the rats showing mechanical hypersensitivity, the mechanical responsiveness of the lumbar dorsal horn neurons was enhanced. A similar increase was observed with the normal lumbar dorsal horn neurons when the GABA-A receptor antagonist bicuculline was topically applied. An i.t. injection of GABA-A or GABA-B receptor agonist, muscimol or baclofen, alleviated the CCD-induced hypersensitivity. Topical application of same drugs attenuated the CCD-induced enhanced mechanical responsiveness of the lumbar dorsal horn neurons. CCD-induced hypersensitivity was also improved by low-dose muscimol applied (i.pl.) into the affected hind paw, whereas no effects could be observed with high-dose muscimol or baclofen.
CONCLUSIONS
The results suggest that the neuropathic pain associated with compression of the dorsal root ganglion is caused by hyperexcitability of the dorsal horn neurons due to a loss of spinal GABAergic inhibition. Peripheral application of low-dose GABA-A receptor agonist can be useful to treat this pain.

Keyword

back pain; compression of dorsal root ganglion; compressive neuropathy; GABA receptor; mechanical hyperalgesia

MeSH Terms

Animals
Back Pain
Baclofen
Bicuculline
GABA-A Receptor Agonists
GABA-A Receptor Antagonists
GABA-B Receptor Agonists
gamma-Aminobutyric Acid
Ganglia, Spinal
Hyperalgesia
Hypersensitivity*
Muscimol
Neuralgia
Posterior Horn Cells
Rats*
Receptors, GABA
Spinal Cord
Baclofen
Bicuculline
GABA-A Receptor Agonists
GABA-A Receptor Antagonists
GABA-B Receptor Agonists
Muscimol
Receptors, GABA
gamma-Aminobutyric Acid