Tibia tumor-induced cancer pain involves spinal p38 mitogen-activated protein kinase activation via TLR4-dependent mechanisms

MCP-1 stimulates spinal microglia via PI3K/Akt pathway in bone cancer pain

“…injections of PI3K inhibitor After the baseline mechanical withdrawal threshold (MWT) test, the rats in BCP group received carcinoma cells (Walker 256 carcinoma cells, 2 Â 105) that were injected into the left tibia cavity as previously described (Liu et al, 2010a(Liu et al, , 2010bYao et al, 2008). To examine the role of PI3K/Akt signaling in the development of BCP, daily i.t.…”

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

“…Furthermore, TLR4 blockade not only prevents the initial development of neuropathic pain (Tanga et al, 2005) but also reverses established neuropathic pain (Bettoni et al, 2008;Hutchinson et al, 2008c;Cao et al, 2009;Lan et al, 2010;Liu et al, 2010a;Saito et al, 2010;Wu et al, 2010). The nociceptive consequences of TLR4-induced central immune signaling are due, at least in part, to p38-dependent activation of reactive glial phenotypes (Liu et al, 2010a) and up-regulation of prosta-NEUROIMMUNOPHARMACOLOGIC IMPLICATIONS FOR OPIOID ANALGESIA glandin E2 and TNF-␣ (Saito et al, 2010). Roles for other TLRs in initiating chronic pain states have also been demonstrated for TLR2 (Kim et al, 2007a;Shi et al, 2011) and TLR3 (Obata et al, 2008).…”

Minocycline‐induced reduction of brain‐derived neurotrophic factor expression in relation to cancer‐induced bone pain in rats

“…For the sham group, saline was intramedullarly injected into the tibia. The surgery was performed as described previously (Yao et al, 2008;Lan et al, 2010;Liu et al, 2010). All animals were allowed to recover from the inoculation surgery for 3 days prior to any experimentation.…”

“…The Walker 256 mammary gland carcinoma cell line, which is syngenic with the SD rat, was cultured in vitro as previously described (Yao et al, 2008;Lan et al, 2010;Liu et al, 2010;Wang et al, 2011). For injection, the cells were collected and diluted to a final concentration of 2 3 10 7 cells/ml and kept on ice until injected into rats.…”

“…Trang et al (2009) showed that ATP activates p38-mitogen-activated protein kinase (p38 MAPK) through P2X4 purinoceptor (P2X4R) in cultured microglia, which leads to the release of BDNF from microglia. The phosphorylated p38-MAPK (p-p38) is localized within hypertrophic spinal microglia in the dorsal horn (Kim et al, 2002;Hua et al, 2005;Liu et al, 2010) and DRG neurons (Ji et al, 2002;Kim et al, 2002). In models of pain after peripheral injury, there is evidence that p-p38 is active in association with microglial activation (Kim et al, 2002;Obata et al, 2004;Tsuda et al, 2004;Hains and Waxman, 2006;Trang et al, 2009).…”