Korean J Pain.  2008 Dec;21(3):173-178. 10.3344/kjp.2008.21.3.173.

Effects of Agmatine on GABAA Receptor Antagonist-induced Tactile Allodynia

• Lee YW
• Ishikawa T

• KMID: 1978704
• DOI: http://doi.org/10.3344/kjp.2008.21.3.173

Abstract

BACKGROUND: The intrathecal (IT) GABAA receptor antagonist, bicuculline (BIC), results in tactile allodynia (TA) through disinhibition in the spinal cord. Such disinhibition is considered to be an important mechanism for neuropathic pain. Agmatine, an endogenous polyamine, has a neuro-protective effect in the central nervous system. We investigated the analgesic effects and mechanisms of agmatine action on BIC-induced TA.
METHODS
Male Sprague-Dawley rats, weighting 250-300 g, were subjected to implantations of PE-10 into the lumbar subarachnoid space for IT drug injection. Five days after surgery, either 10 microliter of normal saline (NS) or agmatine (30 microgram or 10 microgram) in 10 microliter NS were injected 10 min prior to BIC (10 microgram) or NMDA (5 microgram). We assessed the degree of TA (graded 0: no response, 1: mild response, 2: moderate response, 3: strong response) every 5 min for 30 min. Areas under curves and degree of TA were expressed as mean +/- SEM. Results were analyzed using one-way ANOVA followed by a Tukey test for multiple comparisons. P < 0.05 was considered significant.
RESULTS
IT BIC-induced strong TA reached its peak and plateaued between 10 to 15 min. IT NS-NMDA induced mild transient TA for up to 15 min. Preemptive IT AG attenuated IT BIC-induced TA dose dependently and preemptive IT AG10 completely abolished the IT NMDA-induced TA.
CONCLUSIONS
Preemptive IT AG attenuated the IT BIC-induced TA through inhibitory actions on postsynaptic NMDA receptor activation. AG might be a viable therapeutic option in the treatment of neuropathic pain.

Keyword

agmatine; GABAA receptor antagonist; tactile allodynia

MeSH Terms

Agmatine
Bicuculline
Central Nervous System
Humans
Hyperalgesia
Male
N-Methylaspartate
Neuralgia
Nitrogen Mustard Compounds
Rats, Sprague-Dawley
Spinal Cord
Subarachnoid Space
Agmatine
Bicuculline
N-Methylaspartate
Nitrogen Mustard Compounds