Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll-like receptor 4 expression in neuropathic rats.
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 (TLR4) 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 TLR4 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 TLR4 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, TLR4 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.
Department of Physiology, Sabzevar University of Medical Sciences, Sabzevar, Iran.|Department of Neurophysiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Samad
S
Nazemi
Department of Neurophysiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Homa
H
Manaheji
Science Beam Institute, Tehran, Iran.
Syyed Mohammad
SM
Noorbakhsh
Department of Neurophysiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Jalal
J
Zaringhalam
Department of Physiology, Bushehr University of Medical Sciences, Bushehr, Iran.
Mehdi
M
Sadeghi
Department of Physiology, Sabzevar University of Medical Sciences, Sabzevar, Iran.
Mohammad
M
Mohammad-Zadeh
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abbas
A
Haghparast
D000818:Animals; D003250:Constriction; D005071:Evoked Potentials / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000473:pathology; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D008911:Minocycline
WDR neuron; hyperalgesia; microglia; neuropathic pain; toll-like receptor 4