A novel role of minocycline: Attenuating morphine antinociceptive tolerance by inhibition of p38 MAPK in the activated spinal microglia

Chen, Yu; Liao, Xinxue; Liu, Wei; Guo, Ruixian; Wu, Zhao-Zhong; Zhao, Chunshun; Chen, Pei-Xi; Feng, Jianqiang

doi:10.1016/j.bbi.2007.07.014

Cited by 190 publications

(126 citation statements)

References 41 publications

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“…It has been reported that p38 MAPK, a transducer of various extracellular stimuli, regulates the release of inflammatory factors (Saklatvala, 2004) and is involved in the development of morphine analgesic tolerance associated with microglia (Cui et al, 2006(Cui et al, , 2008. Therefore, we examined the effect of p38 MAPK on P2X 7 R-mediated morphine tolerance.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Spinal Microglial P2X7 Receptor in Generation of Tolerance to Morphine Analgesia in Rats

Zhou

Chen²,

Zhang³

2010

Journal of Neuroscience

102

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Morphine loses analgesic potency after repeated administration. The underlying mechanism is not fully understood. Glia are thought to be involved in morphine tolerance, and P2X 7 purinergic receptor (P2X 7 R) has been implicated in neuron-glia communication and chronic pain. The present study demonstrated that P2X 7 R immunoreactivity was colocalized with the microglial marker OX42, but not the astrocytic marker GFAP, in the spinal cord. The protein level of spinal P2X 7 R was upregulated after chronic exposure to morphine. Intrathecal administration of Brilliant Blue G (BBG), a selective P2X 7 R inhibitor, significantly attenuated the loss of morphine analgesic potency, P2X 7 R upregulation, and microglial activation. Furthermore, RNA interference targeting the spinal P2X 7 R exhibited a similar tolerance-attenuating effect. Once morphine analgesic tolerance is established, it was no longer affected by intrathecal BBG. Together, our results suggest that spinal P2X 7 R is involved in the induction but not maintenance of morphine tolerance.

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Section: Discussionmentioning

confidence: 99%

Involvement of Spinal Microglial P2X7 Receptor in Generation of Tolerance to Morphine Analgesia in Rats

Zhou

Chen²,

Zhang³

2010

Journal of Neuroscience

102

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“…Rats with inflammation and their control groups then received daily i.c.v. injections of either minocycline (100 g/5 l/day) (62,63) or saline (5 l/day), beginning at the time of inflammation induction. PTZ-induced seizure susceptibility was determined on day 4.…”

Section: Methodsmentioning

confidence: 99%

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

Riazi

Galic²,

Kuzmiski³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

366

307

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Peripheral inflammation leads to a number of centrally mediated physiological and behavioral changes. The underlying mechanisms and the signaling pathways involved in these phenomena are not yet well understood. We hypothesized that peripheral inflammation leads to increased neuronal excitability arising from a CNS immune response. We induced inflammation in the gut by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to adult male rats. To examine the excitability of the brain in vivo, we administered pentylenetetrazole (PTZ; a GABAergic antagonist) intravenously to evoke clonic seizures. Rats treated with TNBS showed increased susceptibility to PTZ seizures that was strongly correlated with the severity and progression of intestinal inflammation. In vitro hippocampal slices from inflamed, TNBS-treated rats showed increased spontaneous interictal burst firing following application of 4-aminopyridine, indicating increased intrinsic excitability. The TNBS-treated rats exhibited a marked, reversible inflammatory response within the hippocampus, characterized by microglial activation and increases in tumor necrosis factor ␣ (TNF␣) levels. Central antagonism of TNF␣ using a monoclonal antibody or inhibition of microglial activation by i.c.v. injection of minocycline prevented the increase in seizure susceptibility. Moreover, i.c.v. infusion of TNF␣ in untreated rats for 4 days also increased seizure susceptibility and thus mimicked the changes in seizure threshold observed with intestinal inflammation. Our finding of a microglia-dependent TNF␣-mediated increase in CNS excitability provides insight into potential mechanisms underlying the disparate neurological and behavioral changes associated with chronic inflammation.4-aminopyridine ͉ cytokine ͉ pentylenetetrazole ͉ seizure ͉ colitis

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“…1 for summary). Morphine causes phosphorylation of p38 within microglia (Cui et al, , 2008Liu et al, 2006;Wang et al, 2009Wang et al, , 2010aAgostini et al, 2010;Horvath et al, 2010a;Xie et al, 2010;Zhou et al, 2010), in a P2X7- (Zhou et al, 2010), calcitonin generegulated peptide (CGRP)- , and neuronal nitric oxide- (Liu et al, 2006) dependent fashion; this effect could be blocked by naloxone (Xie et al, 2010) and minocycline (Cui et al, 2008). The opioid-selective ligand 2-(3,4-dichlorophenyl)-N-methyl-N-[(1R,2R)-2-pyrrolidin-1-ylcyclohexyl]acetamide (U50488) also causes p38 activation by a classic opioid receptor, which depends on arrestin 3 (Bruchas et al, 2006) and G-protein-coupled receptor kinase 3 .…”

Section: Initiation Of Non-neuronal Cell Intracellular Signaling In Tmentioning

confidence: 99%

Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review of Mechanisms of Central Immune Signaling and Their Implications for Opioid Analgesia

Hutchinson

Shavit

Grace³

et al. 2011

Pharmacol Rev

347

315

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A novel role of minocycline: Attenuating morphine antinociceptive tolerance by inhibition of p38 MAPK in the activated spinal microglia

Cited by 190 publications

References 41 publications

Involvement of Spinal Microglial P2X7 Receptor in Generation of Tolerance to Morphine Analgesia in Rats

Involvement of Spinal Microglial P2X7 Receptor in Generation of Tolerance to Morphine Analgesia in Rats

Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation

Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review of Mechanisms of Central Immune Signaling and Their Implications for Opioid Analgesia

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