Mechanisms of opioid-induced tolerance and hyperalgesia.

Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be unrelated to the original nociceptive stimulus. Complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying opioid tolerance. Pain facilitatory mechanisms in the central nervous system are known to contribute to opioid-induced hyperalgesia. Recent research indicates that there may be overlap in the two conditions. This article reviews known and hypothesized pathophysiologic mechanisms surrounding these phenomena and the clinical implications for pain management nurses.     

Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury. Tumor necrosis factor-alpha (TNFalpha) is protective in LPS-induced preconditioning yet exacerbates neuronal injury in ischemia. Here, we define dual roles of TNFalpha in LPS-induced ischemic tolerance in a murine model of stroke and in primary neuronal cultures in vitro, and show that the cytotoxic effects of TNFalpha are attenuated by LPS preconditioning. We show that LPS preconditioning significantly increases circulating levels of TNFalpha before middle cerebral artery occlusion in mice and show that TNFalpha is required to establish subsequent neuroprotection against ischemia, as mice lacking TNFalpha are not protected from ischemic injury by LPS preconditioning. After stroke, LPS preconditioned mice have a significant reduction in the levels of TNFalpha (approximately threefold) and the proximal TNFalpha signaling molecules, neuronal TNF-receptor 1 (TNFR1), and TNFR-associated death domain (TRADD). Soluble TNFR1 (s-TNFR1) levels were significantly increased after stroke in LPS-preconditioned mice (approximately 2.5-fold), which may neutralize the effect of TNFalpha and reduce TNFalpha-mediated injury in ischemia. Importantly, LPS-preconditioned mice show marked resistance to brain injury caused by intracerebral administration of exogenous TNFalpha after stroke. We establish an in vitro model of LPS preconditioning in primary cortical neuronal cultures and show that LPS preconditioning causes significant protection against injurious TNFalpha in the setting of ischemia. Our studies suggest that TNFalpha is a twin-edged sword in the setting of stroke: TNFalpha upregulation is needed to establish LPS-induced tolerance before ischemia, whereas suppression of TNFalpha signaling during ischemia confers neuroprotection after LPS preconditioning.     

Finding temporary relief: strategy for nursing recruitment in northern aboriginal communities.

To address a recurring shortage of nurses in the aboriginal communities of Northwestern Ontario, the First Nations and Inuit Health Branch, Health Canada, commissioned a study to explore the viability of establishing a relief pool among nurses from nearby small industrial towns. An open/close-ended survey completed by a random sample of 237 nurses from the target population documented levels of awareness, willingness, and preparedness for northern practice, as well as recruitment incentives and disincentives. Findings demonstrate an awareness of the overlap between the professional and personal dimensions characteristic of such practices, and suggest support for innovative rotations that would cut across federal/provincial/community jurisdictions. Although complex, given time and willingness, a regional relief system seems viable.     

Child,family, and system outcomes of intensive case management in New York State

New York State’s Children and Youth Intensive Case Management (CYICM) was implemented in 1988 as one of several community-based initiatives for children with serious emotional disturbance (SED). Underlying this program is the goal of maintaining children with SED in the least restrictive environment appropriate to their needs. This paper presents CYICM child, family, and system outcomes over six years, describes program refinements, and explores continuing research efforts. Data are supportive of the positive outcomes associated with intensive case management for children with SED. Associated with enrollment in CYICM are a decrease in symptoms, improvement in functioning, and fewer hospitalizations in state-operated psychiatric centers, which translates into cost savings and a possible reduction in hospital beds.