Regulation of spinal neuroimmune responses by prolonged morphine treatment in a rat model of cancer induced bone pain

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

“…4 for summary) have also been observed using immunohistochemistry for CD11b (Holdridge et al, 2007;Hutchinson et al, 2009a;Agostini et al, 2010;Mattioli et al, 2010) and ionized calcium binding adaptor molecule-1 (Iba1) Horvath et al, 2010b;Zhou et al, 2010) and confirmed with Western (Mika et al, 2009) and mRNA analysis (Raghavendra et al, 2004a;Tawfik et al, 2005;Cao et al, 2010). Again, significant regional heterogeneity was observed; morphine-induced decreases in CD11b expression were reported in the cornu ammonis of the hippocampus, nucleus accumbens, and substantia nigra, and no change was reported in the dorsal raphe nucleus and medial prefrontal cortex (Hutchinson et al, 2009a).…”

“…Best known of the immune signaling proteins are the cytokines, especially the proinflammatory cytokines IL-1␤, IL-6, and TNF-␣, all of which show up-regulation of transcription, translation, and release after morphine administration. IL-1␤ is elevated by morphine (Johnston et al, 2004;Bokhari et al, 2009;Cao et al, 2010), in a ceramide synthase- , sphingosine kinase- (Muscoli et al, 2010), MEK-, and CGRP- ) dependent manner; this effect could be blocked by ibudilast (Hutchinson et al, 2009a), propentofylline (Raghavendra et al, 2004a), and amitriptyline (Tai et al, 2006;Tai et al, 2009), as well as by the blockade of TNF-␣ (etanercept) (Shen et al, 2011). IL-6 elevation after morphine (Johnston et al, 2004;Dave and Khalili, 2010) is dependent on sphingosine kinase (Muscoli et al, 2010), p38, CGRP , and TLR2 and could also be blocked by etanercept (Shen et al, 2011), naltrexone (Bokhari et al, 2009), amitriptyline (Tai et al, 2006;Tai et al, 2009), and propentofylline (Raghavendra et al, 2004a).…”

Transgenerational modification of hippocampus TNF-α and S100B levels in the offspring of rats chronically exposed to morphine during adolescence

“…Chronic administration of opioids induces functional interactions between the immune and nervous systems (41)(42)(43)(44). Some factors of the immune system (such as TNF-α, IL-1β, IL-6, and NF-KB) show modifications due to chronic morphine exposure, and these modifications affect hippocampus function (45,46).…”

Acute opioid administration induces hypothalamic–pituitary–adrenal activation and is mediated by genetic variation in interleukin (Il)1B

“…Given the ability of IL-1β to influence the HPA axis, this study also aimed to assess the impact of IL1B genetic variability on HPA axis response to opioid administration. Opioid administration has been documented to reproducibly elevate IL-1β levels in animal models (Bokhari et al, 2009;Cao et al, 2010). Therefore, the hypothesis of this study was that variability in IL1B that may modify the expression and/or function of IL-1β could in turn alter the HPA axis response to opioid administration.…”