Korean J Physiol Pharmacol.  2008 Oct;12(5):237-243. 10.4196/kjpp.2008.12.5.237.

Spinal Metabotropic Glutamate Receptors (mGluRs) are Involved in the Melittin-induced Nociception in Rats

• Cho CH
• Shin HK

• KMID: 1486105
• DOI: http://doi.org/10.4196/kjpp.2008.12.5.237

Abstract

Intraplantar injection of melittin has been known to induce sustained decrease of mechanical threshold and increase of spontaneous flinchings. The present study was undertaken to investigate how the melittin-induced nociceptive responses were modulated by changes of metabotropic glutamate receptor (mGluR) activity. Changes in paw withdrawal threshold (PWT), number of flinchings and paw thickness were measured at a given time point after injection of melittin (10microgram/paw) into the mid-plantar area of rat hindpaw. To observe the effects of mGluRs on the melittin-induced nociceptions, group I mGluR (AIDA, 100microgram and 200microgram), mGluR1 (LY367385, 50microgram and 100microgram) and mGluR5 (MPEP, 200microgram and 300microgram) antagonists, group II (APDC, 100microgram and 200microgram) and III (L-SOP, 100microgram and 200microgram) agonists were intrathecally administered 20 min before melittin injection. Intraplantar injection of melittin induced a sustained decrease of mechanical threshold, spontaneous flinchings and edema. The effects of melittin to reduce mechanical threshold and to induce spontaneous flinchings were significantly suppressed following intrathecal pre-administration of group I mGluR, mGluR1 and mGluR5 antagonists, group II and III mGluR agonists. Group I mGluR antagonists and group II and III mGluR agonists had no significant effect on melittin-induced edema. These experimental findings indicate that multiple spinal mGluRs are involved in the modulation of melittin-induced nociceptive responses.

Keyword

Spinal metabotropic glutamate receptors; Melittin; Nociceptive responses

MeSH Terms

Animals
Edema
Melitten
Nociception
Rats
Receptors, Metabotropic Glutamate
Melitten
Receptors, Metabotropic Glutamate

Figure

• 

  Fig. 1. Intraplantar injection of melittin (10 μg/paw, -•-, n=12) caused prolonged decrease of mechanical threshold which was significantly attenuated in the rats pretreated with group I meta-botropic glutamate receptor (mGluR) antagonist, [(RS)-1-aminoindan-1,5-dicarboxylic acid, AIDA, 100 μg, -▴-, n=10; 200 μ g, -▪-, n=11]. Data are expressed as mean±S.E. ∗p<0.05, ∗∗p<0.01, ∗∗∗p < 0.001, significant differences from melittin-induced decrease in mechanical threshold.

• 

  Fig. 2. Intrathecal injection of metabotropic glutamate receptor 1 (mGluR1) antagonist, (LY367385, 50 μg, -□-, n=10; 100 μg, -▪-, n=11) and mGluR5 antagonist, [2-methyl-6 (phenylethnyl) pyridine hydrochloride, MPEP, 200 μ g, -Δ-, n=9; 300 μg, -Δ-, n=10] attenuated the effect of melittin (10 μ g/paw, -•-) to reduce mechanical threshold. Data are expressed as mean±S.E. ∗p<0.05 ∗∗p<0.01, ∗∗∗p<0.001, significant differences from melittin-induced decrease in mechanical threshold.

• 

  Fig. 3. The effect of melittin (10 μg/paw, -•-) to reduce mechanical threshold was suppressed in the rats which received intrathecal pre-injection of group II metabotropic glutamate receptor (mGluR) agonist [(2R,4R)-4- aminopyrrolidine-2,4-dicarboxylate, APDC, 100 μg, -Δ-, n=9; 200 μg, -▪-, n=10)]. Data are expressed as mean±S.E. ∗p<0.01, ∗∗p< 0.001, significant differences from melittin-induced decrease in the mechanical threshold.

• 

  Fig. 4. Melittin-induced decrease in the mechnical threshold (10 μg/paw, -•-) was attenuated in the rats intrathecally administered with group III metabotropic glutamate receptor (mGluR) agonist, O-phospho-L-Serine (L- SOP, 100 μg, -Δ-, n=12; 200 μg, -Δ-, n=12). Data are expressed as mean±S.E. ∗p<0.01, ∗∗p<0.001, significant differences from melittin-induced decrease in the mechanical threshold.

• 

  Fig. 5. Melittin-induced (10μg/paw) spontaneous flinchings were dose-dependently inhibited in the rats pre-treated with group I metabotropic glutamate receptors (mGluRs) (AIDA, 100μg & 200μg), mGluR1 (LY367385, 50μg & 100μg), and mGluR5 (MPEP, 200 μg & 300μg) antagonist, group II (APDC, 100μg & 200μg) and group III (L-SOP, 100μg & 200μg) mGluR agonist. Data are expressed as mean±S.E. ∗p<0.01, ∗∗p< 0.001, significant differences from melittin- induced increase in flinching behaviors.

• 

  Fig. 6. Intraplantar injection of melittin (10 μg/paw) caused increases of paw thickness which were not changed following intra-thecal pre-administration of group I metabotropic glutamate receptor (mGluR) antagonist (AIDA, 200μg; MPEP, 300μg; LY367385, 100 μg), group II (APDC, 200μg) and group III (L-SOP, 200μg) mGluR agonist. Data are expressed as mean±S.E.

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