Scientific reports
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Neural responses to incentives are altered in chronic pain and by opioid use. To understand how opioid use modulates the neural response to reward/value in chronic pain, we compared brain functional magnetic resonance imaging (fMRI) responses to a monetary incentive delay (MID) task in patients with fibromyalgia taking opioids (N = 17), patients with fibromyalgia not taking opioids (N = 17), and healthy controls (N = 15). ⋯ However, neural responses in the medial prefrontal cortex differed, such that patients with fibromyalgia not taking opioids demonstrated significantly altered responses to anticipated rewards and non-loss outcomes compared to healthy controls, but patients with fibromyalgia taking opioids did not. Despite limitations including the use of additional non-opioid medications by fibromyalgia patients taking opioids, these preliminary findings suggest relatively "normalized" neural responses to monetary incentives in chronic pain patients who take opioids versus those who do not.
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Preterm brain injury is highly associated with inflammation, which is likely related in part to sterile responses to hypoxia-ischemia. We have recently shown that neuroprotection with inflammatory pre-conditioning in the immature brain is associated with induction of toll-like receptor 7 (TLR7). We therefore tested the hypothesis that central administration of a synthetic TLR7 agonist, gardiquimod (GDQ), after severe hypoxia-ischemia in preterm-equivalent fetal sheep would improve white and gray matter recovery. ⋯ Central infusion of GDQ was associated with a robust increase in fetal plasma concentrations of the anti-inflammatory cytokines, interferon-β (IFN-β) and interleukin-10 (IL-10), with no significant change in the concentration of the pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α). In conclusion, delayed administration of the TLR7 agonist, GDQ, after severe hypoxia-ischemia in the developing brain markedly ameliorated white and gray matter damage, in association with upregulation of anti-inflammatory cytokines. These data strongly support the hypothesis that modulation of secondary inflammation may be a viable therapeutic target for injury of the preterm brain.