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Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll‐like receptor 4 expression in neuropathic rats
Author(s) -
Nazemi Samad,
Manaheji Homa,
Noorbakhsh Syyed Mohammad,
Zaringhalam Jalal,
Sadeghi Mehdi,
MohammadZadeh Mohammad,
Haghparast Abbas
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12414
Subject(s) - microglia , neuroscience , toll like receptor , neuron , receptor , toll , neuropathic pain , medicine , chemistry , pharmacology , biology , inflammation , immunology , innate immune system
Summary It is believed that neuropathic pain results from aberrant neuronal discharges although some evidence suggests that the activation of glia cells contributes to pain after an injury to the nervous system. This study aimed to evaluate the role of microglial activation on the hyper‐responsiveness of wide dynamic range neurons ( WDR ) and Toll‐like receptor 4 ( TLR 4) expressions in a chronic constriction injury ( CCI ) model of neuropathic pain in rats. Adult male Wistar rats (230 ± 30 g) underwent surgery for induction of CCI neuropathy. Six days after surgery, administration of minocycline (10, 20, and 40 mg/kg, i.p.) was initiated and continued until day 14. After administration of the last dose of minocycline or saline, a behavioral test was conducted, then animals were sacrificed and lumbar segments of the spinal cord were collected for Western blot analysis of TLR 4 expression. The electrophysiological properties of WDR neurons were investigated by single unit recordings in separate groups. The findings showed that after CCI , in parallel with thermal hyperalgesia, the expression of TLR 4 in the spinal cord and the evoked response of the WDR neurons to electrical, mechanical, and thermal stimulation significantly increased. Post‐injury administration of minocycline effectively decreased thermal hyperalgesia, TLR 4 expression, and hyper‐responsiveness of WDR neurons in CCI rats. The results of this study indicate that post‐injury, repeated administration of minocycline attenuated neuropathic pain by suppressing microglia activation and reducing WDR neuron hyper‐responsiveness. This study confirms that post‐injury modulation of microglial activity is a new strategy for treating neuropathic pain.