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Accumulated evidence suggests that the C-C motif chemokine ligand 5 (CCL5) modulates migration of inflammatory cells in several pathological conditions. This study tested the hypothesis that lack of CCL5 would modulate the recruitment of inflammatory cells to painful, inflamed sites and could attenuate pain in a murine chronic neuropathic pain model. Nociceptive sensitization, immune cell infiltration, multiple cytokine expression, and opioid peptide expression in damaged nerves were studied in wild-type (CCL5 +/+) and CCL5-deficient (CCL5 -/-) mice after partial sciatic nerve ligation (PSNL). Results indicated that CCL5 -/- mice had less behavioral hypersensitivity after PSNL. Macrophage infiltration and proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and interferon-γ) in damaged nerves following PSNL were significantly decreased in CCL5 -/- mice. Conversely, several antiinflammatory cytokine (IL-4 and IL-10) proteins were significantly increased in CCL5 -/- animals and the expression of enkephalin, β-endorphin, and dynorphin mRNA was significantly lower than in wild-type control mice. These results represent the first evidence that CCL5 is capable of regulating the pathway that controls hyperalgesia at the level of the peripheral injured site in a murine chronic neuropathic pain model. We demonstrated that lack of CCL5 modulated cell infiltration and the proinflammatory milieu within the injured nerve. Attenuated behavioral hypersensitivity in CCL5 -/- mice observed in the current study could be a result of decreased macrophage infiltration, mobilization, and functional ability at injured sites. Collectively, the present study results suggest that CCL5 receptor antagonists may ultimately provide a novel class of analgesics for therapeutic intervention in chronic neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: The authors conducted this prospective study to determine the incidence, potential routes, and risk factors of microbial colonization of epidural catheter used for postoperative pain control., Methods: Two-hundred five patients with epidural analgesia for postoperative pain were studied. On removal of the catheter, five samples were sent for culture: the infusate, a swab from inside the hub of the epidural catheter connector, a swab from the skin around the catheter insertion site, the subcutaneous segment, and the tip of the catheter. Clinical data related to the catheter insertion, management, and general patient conditions were collected., Results: The positive culture rates for the subcutaneous and tip segments of the catheter were 10.5% and 12.2%, respectively. The most common organism in the culture was coagulase-negative staphylococcus. There was a strong linear relationship between bacterial colonization in the skin around the catheter insertion site and growth from the subcutaneous and tip segments of catheter (P = 0.000). Catheter-related events at ward, blood transfusion, and positive culture from the skin at the insertion site were risk factors for bacterial colonization of epidural catheters. Inflammation at catheter insertion site, catheter indwelling time, and level of catheter insertion were not predicators for epidural catheter colonization., Conclusions: The authors' results suggest that bacterial migration along the epidural catheter track is the most common route of epidural catheter colonization. Maintaining sterile skin around the catheter insertion site will reduce colonization of the epidural catheter tip.

Background: A period of hypothermia before ischemia (hypothermic preconditioning) induces a delayed phase of ischemic tolerance in rat brain. However, whether hypothermic preconditioning induces an acute phase (within a few hours after the hypothermia) of ischemic tolerance remains unknown. This study was designed to determine the time window of the hypothermic preconditioning-induced acute phase of neuroprotection, which is useful information for situations during surgery with anticipated ischemic episodes, and its involved mechanisms., Methods: Survival of Purkinje cells in rat cerebellar slices was evaluated after a 20-min oxygen-glucose deprivation (OGD, in vitro simulated ischemia) followed by a 4-h recovery. Mild hypothermia (33 degrees C) for 20 min was applied at various times before the OGD., Results: The hypothermia applied immediately to 3 h before the OGD equally effectively reduced OGD-induced Purkinje cell death/injury. Glibenclamide, a selective KATP channel blocker; 8-cyclopentyl-1,3-dipropylxanthine, a selective adenosine A1 receptor antagonist; and farnesyl protein transferase inhibitor III, a selective inhibitor to reduce Ras farnesylation, abolished hypothermic preconditioning-induced neuroprotection when applied during the hypothermia. OGD increased the expression of high-mobility group I(Y) proteins, which are nuclear transcription factors to enhance the expression of putatively damaging proteins such as cyclooxygenase-2, in cerebellar slices. This increase was attenuated by hypothermic preconditioning., Conclusions: Hypothermic preconditioning induces an acute phase of neuroprotection. This neuroprotection depends on activation of the signaling molecules, adenosine A1 receptors, KATP channels, and Ras. Inhibition of putatively damaging proteins via the effects of hypothermic preconditioning on high-mobility group I(Y) expression may also be involved in hypothermic preconditioning-induced neuroprotection.