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

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

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 (10Ռg/paw) into the mid-plantar area of rat hindpaw. To observe the effects of mGluRs on the melittin-induced nociceptions, group I mGluR (AIDA, 100Ռg and 200Ռg), mGluR₁ (LY367385, 50Ռg and 100Ռg) and mGluR₅ (MPEP, 200Ռg and 300Ռg) antagonists, group II (APDC, 100Ռg and 200Ռg) and III (L-SOP, 100Ռg and 200Ռg) 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.