Post-injury repeated administrations of minocycline improve the antinociceptive effect of morphine in chronic constriction injury model of neuropathic pain in rat

Samad, Noreen; Manaheji, Homa; Zaringhalam, Jalal; Sadeghi, Mehdi; Haghparast, Abbas

doi:10.1016/j.pbb.2012.07.001

Cited by 26 publications

(25 citation statements)

References 38 publications

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“…The main causes of painful neuropathy are still unknown; many studies have established that microglia are involved in the initiation and maintenance of chronic and neuropathic pain. Additionally, inhibition of microglial activity effectively attenuates the behavioral symptoms of neuropathic pain …”

Section: Discussionmentioning

confidence: 99%

Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll‐like receptor 4 expression in neuropathic rats

Samad

Manaheji

Noorbakhsh³

et al. 2015

Clin Exp Pharma Physio

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SUMMARYIt 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 AE 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 hyperresponsiveness 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 hyperresponsiveness. This study confirms that post-injury modulation of microglial activity is a new strategy for treating neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll‐like receptor 4 expression in neuropathic rats

Samad

Manaheji

Noorbakhsh³

et al. 2015

Clin Exp Pharma Physio

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“…injection of PBS or minocycline (40 mg/kg) [24], a broad-spectrum tetracycline antibiotic that exerts multiple anti-inflammatory effects, including microglial inhibition, 7 days before PD induction and for the following 14 consecutive days after the lesion. Minocycline (Sigma, St. Louis, MO) was dissolved in sterile water and sonicated to ensure complete solubilization.…”

Section: Methodsmentioning

confidence: 99%

Microglial Cells Are Involved in the Susceptibility of NADPH Oxidase Knockout Mice to 6-Hydroxy-Dopamine-Induced Neurodegeneration

et al. 2013

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We explored the impact of Nox-2 in modulating inflammatory-mediated microglial responses in the 6-hydroxydopamine (6-OHDA)-induced Parkinson’s disease (PD) model. Nox1 and Nox2 gene expression were found to increase in striatum, whereas a marked increase of Nox2 expression was observed in substantia nigra (SN) of wild-type (wt) mice after PD induction. Gp91phox-/- 6-OHDA-lesioned mice exhibited a significant reduction in the apomorphine-induced rotational behavior, when compared to wt mice. Immunolabeling assays indicated that striatal 6-OHDA injections reduced the number of dopaminergic (DA) neurons in the SN of wt mice. In gp91phox-/- 6-OHDA-lesioned mice the DA degeneration was negligible, suggesting an involvement of Nox in 6-OHDA-mediated SN degeneration. Gp91phox-/- 6-OHDA-lesioned mice treated with minocycline, a tetracycline derivative that exerts multiple anti-inflammatory effects, including microglial inhibition, exhibited increased apomorphine-induced rotational behavior and degeneration of DA neurons after 6-OHDA injections. The same treatment also increased TNF-α release and potentiated NF-κB activation in the SN of gp91phox-/--lesioned mice. Our results demonstrate for the first time that inhibition of microglial cells increases the susceptibility of gp91phox-/- 6-OHDA lesioned mice to develop PD. Blockade of microglia leads to NF-κB activation and TNF-α release into the SN of gp91phox-/- 6-OHDA lesioned mice, a likely mechanism whereby gp91phox-/- 6-OHDA lesioned mice may be more susceptible to develop PD after microglial cell inhibition. Nox2 adds an essential level of regulation to signaling pathways underlying the inflammatory response after PD induction.

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“…The principles of these methods may be applied to nerves other than the sciatic, such as orofacial nerves [202]. The behavioral phenotypes are essentially indistinguishable between these different peripheral nerve models, with decreased withdrawal thresholds to mechanical and thermal stimuli and spontaneous guarding behavior of affected limbs [132;189]. Furthermore, there are changes in non-reflexive (spontaneous) pain in animals with nerve injury: vocalization [101], change in spontaneous motor activity [69], conditioned place preference (CPP) [75;98], escape avoidance (PEAP)[106] social behavior such as dominance [126].…”

Section: Animal Models Of Diseasementioning

confidence: 99%

An Overview of Animal Models of Pain: Disease Models and Outcome Measures

Gregory

Harris

Robinson

et al. 2013

The Journal of Pain

333

255

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Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined. A number of animal models have been developed, reflecting observations that pain phenotypes are mediated by distinct mechanisms. Animal models of pain are designed to mimic distinct clinical diseases to better evaluate underlying mechanisms and potential treatments. Outcome measures are designed to measure multiple parts of the pain experience including reflexive hyperalgesia measures, sensory and affective dimensions of pain and impact of pain on function and quality of life. In this review we discuss the common methods used for inducing each of the pain phenotypes related to clinical pain syndromes, as well as the main behavioral tests for assessing pain in each model.

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Post-injury repeated administrations of minocycline improve the antinociceptive effect of morphine in chronic constriction injury model of neuropathic pain in rat

Cited by 26 publications

References 38 publications

Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll‐like receptor 4 expression in neuropathic rats

Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll‐like receptor 4 expression in neuropathic rats

Microglial Cells Are Involved in the Susceptibility of NADPH Oxidase Knockout Mice to 6-Hydroxy-Dopamine-Induced Neurodegeneration

An Overview of Animal Models of Pain: Disease Models and Outcome Measures

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