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Background: Low back pain (LBP) is the leading global cause of disability and is associated with intervertebral disc degeneration (DD) in some individuals. However, many adults have DD without LBP. Understanding why DD is painful in some and not others may unmask novel therapies for chronic LBP. The objectives of this study were to a) identify factors in human cerebrospinal fluid (CSF) associated with chronic LBP and b) examine their therapeutic utility in a proof-of-concept pre-clinical study. Methods: Pain-free human subjects without DD, pain-free human subjects with DD, and patients with chronic LBP linked to DD were recruited and lumbar MRIs, pain and disability levels were obtained. CSF was collected and analyzed by multiplex cytokine assay. Interleukin-8 (IL-8) expression was confirmed by ELISA in CSF and in intervertebral discs. The SPARC-null mouse model of progressive, age-dependent DD and chronic LBP was used for pre-clinical validation. Male SPARC-null and control mice received systemic Reparixin, a CXCR1/2 (receptors for IL-8 and murine analogues) inhibitor, for 8 weeks. Behavioral signs of axial discomfort and radiating pain were assessed. Following completion of the study, discs were excised and cultured, and conditioned media was evaluated with a protein array. Findings: IL-8 was elevated in CSF of chronic LBP patients with DD compared to pain-free subjects with or without DD. Chronic inhibition with reparixin alleviated low back pain behaviors and attenuated disc inflammation in SPARC-null mice. Interpretation: These studies suggest that the IL-8 signaling pathway is a viable therapy for chronic LBP. Fund: Supported by NIH, MMF, CIHR and FRQS.

To determine which of three types of rectal sedation was most effective preoperatively in facilitating parental separation and intravenous cannulation in young children, 100 children 3.0 +/- 1.7 (mean +/- SD) yr of age were randomly assigned to four equal groups. One group (M-K-A) received rectal midazolam (0.5 mg/kg), ketamine (3 mg/kg), and atropine (0.02 mg/kg). The other sedation groups received the same doses of midazolam and atropine (M-A) or ketamine and atropine (K-A) alone, and the control group (A) received only rectal atropine. Most children in either the M-K-A (100%) or M-A (92%) groups separated easily from their parents without struggling or crying, significantly more than in the K-A (60%) or A (64%) groups. However, more children in the M-K-A group (44%) were asleep during separation than in the M-A group (8%; P < 0.05). Only 20% of the children in the M-A or M-K-A groups cried during intravenous catheter placement, significantly less than in the K-A (56%) or A (92%) groups. Intravenous catheter placement was also successful significantly more often in the M-A (80%) and M-K-A (84%) groups than in the K-A (48%) or A (40%) groups. Complications were similar among the groups, but there was evidence that midazolam prolonged recovery time in some patients. Rectal midazolam with or without ketamine is a useful technique when intravenous catheter placement before induction of anesthesia is desired.

Sodium nitroprusside has been used in clinical practice as an arterial and venous vasodilator for 40 years. This prodrug reacts with physiologic sulfhydryl groups to release nitric oxide, causing rapid vasodilation, and acutely lowering blood pressure. It is used clinically in cardiac surgery, hypertensive crises, heart failure, vascular surgery, pediatric surgery, and other acute hemodynamic applications. In some practices, newer agents have replaced nitroprusside, either because they are more effective or because they have a more favorable side-effect profile. However, valid and adequately-powered efficacy studies are sparse and do not identify a superior agent for all indications. The cyanide anion release concurrent with nitroprusside administration is associated with potential cyanide accumulation and severe toxicity. Agents to ameliorate the untoward effects of cyanide are limited by various problems in their practicality and effectiveness. A new orally bioavailable antidote is sodium sulfanegen, which shows promise in reversing this toxicity. The unique effectiveness of nitroprusside as a titratable agent capable of rapid blood pressure control will likely maintain its utilization in clinical practice for the foreseeable future. Additional research will refine and perhaps expand indications for nitroprusside, while parallel investigation continues to develop effective antidotes for cyanide poisoning.