Pain
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This study assessed functional brain activation in rats during expectation of visceral pain. Male rats were trained in step-down passive avoidance (PA) for 2 days. Upon stepping down from a platform, conditioned animals received noxious colorectal distension delivered through a colorectal balloon, whereas the balloon in control rats remained uninflated. ⋯ The amygdala and cerebellar hemispheres formed another positively connected cluster, which was negatively connected with the corticostriatal cluster, suggesting corticolimbic modulation. Prelimbic cortex, nucleus accumbens, and anterior insula emerged in conditioned animals as hubs. Our results show that during retrieval of PA, brain areas implicated in PA expression as well as those implicated in acute visceral pain processing were recruited, in line with findings from human brain imaging studies on pain expectation.
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Persistent pain after resolution of clinically appreciable signs of arthritis poses a therapeutic challenge, and immunosuppressive therapies do not meet this medical need. To investigate this conversion to persistent pain, we utilized the K/BxN serum transfer arthritis model, which has persistent mechanical hypersensitivity despite the resolution of visible inflammation. Toll-like receptor (TLR) 4 has been implicated as a potential therapeutic target in neuropathic and other pain models. ⋯ WT arthritic mice had reduced spinal levels of the anti-inflammatory prostaglandin 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) on day 6, compared to IT LPS-RS-treated mice. Direct IT application of 15d-PGJ(2) (0.5 μg) on day 6 improved mechanical hypersensitivity in arthritic mice within 15 min. Hence, TLR4 signaling altered spinal bioactive lipid profiles in the serum transfer model and played a critical role in the transition from acute to chronic postinflammatory mechanical hypersensitivity.
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This study investigated the effects of pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K)γ in the pruriceptive, inflammatory, and nociceptive responses induced by trypsin in mice. The animals were orally treated with the selective PI3Kγ inhibitor AS605240 (0.3-30 mg/kg) 30 minutes beforehand. In separate groups, AS605240 was given by intrathecal (i.t.) or intracerebroventricular (i.c.v.) routes. ⋯ In contrast, the oral administration of AS605240 did not significantly modify capsaicin-evoked nociception, although this inhibitor was effective when dosed by i.c.v. route. Noteworthy, AS605240 (1mg/kg) was able to prevent c-Fos and phospho-Akt immunopositivity at the spinal cord of trypsin-injected mice, either into the back of the neck or the paws. To conclude, PI3Kγ inhibition might well represent a valuable alternative for treating inflammatory and painful conditions, as well as pruritus.
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Multicenter Study
The mediating role of pain in substance use and depressive symptoms among Multicenter AIDS Cohort Study (MACS) participants.
Pain in human immunodeficiency virus (HIV) frequently co-occurs with substance use and depression. The complex associations among patient characteristics, pain, depression, and drug use in HIV suggests a role for testing models that can account for relationships simultaneously, control for HIV status, and also test for mediation. Using structural equation modeling, the current study examined associations among pain, sociodemographics, illicit drug use, and depressive symptoms in 921 HIV-seropositive and 1019 HIV-seronegative men from the Multicenter AIDS Cohort Study, an ongoing prospective study of the natural history of HIV infection among gay/bisexual men. ⋯ HIV-seropositive status predicted more use of inhaled nitrites. In this cohort, having lower CD4+ cell counts (predicted by HIV status), being African American, less educated, and older were all associated with more pain, which, in turn, was associated with more illicit drug use and more depressive symptoms. The results underscore the need for adequate pain management, particularly among vulnerable subgroups of HIV-seropositive and HIV-seronegative men to reduce the risk of drug use and depression.