J Korean Med Sci.  2011 Oct;26(10):1371-1377. 10.3346/jkms.2011.26.10.1371.

Pharmacology of Intracisternal or Intrathecal Glycine, Muscimol, and Baclofen in Strychnine-induced Thermal Hyperalgesia of Mice

• Lee IO
• Son JK
• Lim ES
• Kim YS

• KMID: 1785997
• DOI: http://doi.org/10.3346/jkms.2011.26.10.1371

Abstract

Glycine and gamma-aminobutyric acid (GABA) are localized and released by the same interneurons in the spinal cord. Although the effects of glycine and GABA on analgesia are well known, little is known about the effect of GABA in strychnine-induced hyperalgesia. To investigate the effect of GABA and the role of the glycine receptor in thermal hyperalgesia, we designed an experiment involving the injection of muscimol (a GABAA receptor agonist), baclofen (a GABAB receptor agonist) or glycine with strychnine (strychnine sensitive glycine receptor antagonist). Glycine, muscimol, or baclofen with strychnine was injected into the cisterna magna or lumbar subarachnoidal spaces of mice. The effects of treatment on strychnine-induced heat hyperalgesia were observed using the pain threshold index via the hot plate test. The dosages of experimental drugs and strychnine we chose had no effects on motor behavior in conscious mice. Intracisternal or intrathecal administration of strychnine produced thermal hyperalgesia in mice. Glycine antagonize the effects of strychnine, whereas, muscimol or baclofen does not. Our results indicate that glycine has anti-thermal hyperalgesic properties in vivo; and GABA receptor agonists may lack the binding abilities of glycine receptor antagonists with their sites in the central nervous system.

Keyword

Hyperalgesia; Strychnine; Gamma-Aminobutyric Acid; Intracisternal; Intrathecal Drug Delivery

MeSH Terms

Animals
Baclofen/*administration & dosage/pharmacology
Drug Delivery Systems
GABA Agonists/administration & dosage/pharmacology
GABA Antagonists/administration & dosage/pharmacology
Glycine/*administration & dosage/pharmacology
Hot Temperature
Hyperalgesia/chemically induced/*drug therapy
Injections, Spinal
Male
Mice
Mice, Inbred ICR
Muscimol/*administration & dosage/pharmacology
Pain Threshold
Random Allocation
Strychnine
gamma-Aminobutyric Acid/metabolism

Figure

• 

  Fig. 1 Effect of strychnine or artificial cerebrospinal fluid (aCSF) on hot plate test pain index (HPPI). Strychnine (0.16715 µg) or aCSF was injected intracisternally (IC, A) or intrathecally (IT, B). Data are expressed as mean ± SEM. *P < 0.05 vs vehicle (aCSF) controls by the t-test; †P < 0.05 vs basal time point (time = 0) by repeated measures ANOVA (n = 8 mice per group).

• 

  Fig. 2 Effect of glycine on HPPI in strychnine treated mice. Glycine (5, 10, and 25 µg) with strychnine (0. 16715 µg) was injected intracisternally (IC, A) or intrathecally (IT, B). Data are expressed as mean ± SEMs. *P < 0.05 vs the strychnine + aCSF group by two-way ANOVA, Dunn's test, or the Holm-Sidak method (n = 8 mice per group). †P < 0.05 vs. basal time point (time = 0) by repeated measures ANOVA (n = 8 mice per group).

• 

  Fig. 3 Effect of muscimol on HPPI in strychnine treated mice. Muscimol (0.01, 0.02, or 0.1 µg) with strychnine (0.16715 µg) was injected intracisternally (IC, A) or intrathecally (IT, B). Data are expressed as means ± SEMs (n = 8 mice per group).

• 

  Fig. 4 Effect of baclofen on HPPI in strychnine treated mice. Baclofen (0.001, 0.002, or 0.01 µg) with strychnine (0.16715 µg) was injected intracisternally (IC, A) or intrathecally (IT, B). Data are expressed as means ± SEMs (n = 8 mice per group).

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