n-n--dibenzhydrylethane-1-2-diamine-dihydrochloride and Sciatica

Metabotropic glutamate (mGlu) receptors, which are present on neurons and glial cells, have been shown to play a role in neuropathic pain. The present study sought to investigate how the glial inhibitors minocycline and pentoxifylline alter the effect that chronic constriction injury (CCI) has on the expression of mGlu receptors and on their associated ligands. RT-PCR analysis revealed that seven days after CCI, the mRNA levels of glial markers C1q and GFAP, as well as those of mGlu5 and mGlu3, but not mGlu7, were elevated in the lumbar spinal cord - ipsilateral to the injury. The protein levels of the microglial marker OX42, the astroglial marker GFAP, and mGlu5 receptor protein were increased, whereas the levels of mGlu2/3 and mGlu7 receptor proteins were reduced. Preemptive and repeated intraperitoneal (i.p.) administration (16 and 1h before nerve injury and then twice daily for seven days) of minocycline (30mg/kg) and pentoxifylline (20mg/kg) prevented the injury-induced changes in the levels of mGlu3 and mGlu5 receptor mRNAs and the injury-induced changes in the protein levels of all the receptors. Repeated administration of minocycline and pentoxifylline significantly attenuated CCI-induced allodynia (von Frey test) and hyperalgesia (cold plate test) measured on day seven after injury and potentiated the antiallodynic and antihyperalgesic effects of single i.p. and intrathecal (i.t.) injections of mGlu receptor ligands: MPEP, LY379268 or AMN082. We conclude that attenuation of injury-induced glial activation can reduce glutamatergic activity, thereby contributing to regulation of pain sensation.

Topics: Amino Acids; Analysis of Variance; Animals; Benzhydryl Compounds; Bridged Bicyclo Compounds, Heterocyclic; CD11b Antigen; Complement C1q; Disease Models, Animal; Drug Administration Schedule; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Functional Laterality; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hyperalgesia; Male; Mice; Minocycline; Pain Measurement; Pain Threshold; Pentoxifylline; Pyridines; Receptors, Metabotropic Glutamate; RNA, Messenger; Sciatica; Spinal Cord