Intragastric balloon therapy was relatively innocuous and associated with successful weight loss and maintenance at 2.5 years in a quarter of participants. It represents a valid option for weight loss.

Chronic pain is one of the most common reasons for patients to seek medical care. Chronic pain results in substantial economic losses and remains one of the most costly conditions in modern western society. In 1991, costs were estimated to be approximately $65 billion annually, comparable to the cost of treating diabetes. Persistent chronic pain and the use of advanced interventional and pharmacological treatments often leads to complex social and psychological maladaptations, health care overutilization, as well as many other substantial direct and indirect costs. Thus, the proper treatment of chronic pain involves intense multidisciplinary management, including pharmacological, behavioral, and psychological interventions. Few studies have assessed the total economic cost of chronic pain. However, many of the chronic pain treatments do not alleviate pain symptoms for most patients and lead to unsuccessful application of resources. The economic consequences of inadequately treated chronic pain translates into lost work days, overutilization of health care resources (excess hospitalizations, and surgical procedures and inappropriate medications) and other out-of-pocket patient expenses. Increasing emphasis on diagnosis and treatment of chronic pain places more importance on the need for efficient and coordinated management of patient with chronic pain. The management of chronic pain is remarkably complex and resource intensive. Therefore, a clear need exists for intensive pharmacoeconomic investigations, specifically evaluating costs related to chronic pain and the associated treatment modalities. Additionally, evaluation of the costs related to chronic pain would measure the economic burden of chronic pain, including an estimate of the amount that could potentially be saved if chronic pain patients are optimally managed.

In a model for neuronal movement, PC12 cells undergo fast migration in response to nerve growth factor (NGF) and phorbol ester (PMA). We previously showed that NGF increases intracellular cAMP via activation of soluble adenylyl cyclase (sAC). In this report, we demonstrate that sAC activation is an essential component of NGF-+PMA-induced fast migration in PC12 cells. Interestingly, PMA also raises intracellular cAMP but does so by stimulating transmembrane adenylyl cyclases (tmAC); however, this tmAC-generated cAMP does not contribute to fast migration. Therefore, cells must possess independent pools of cAMP capable of modulating distinct functions.Keywords adenylyl cyclase; nerve growth factor; neuron; compartmentalization; protein kinase C Neuronal migration and differentiation constitute key processes in the development of the central nervous system. The rat pheochromocytoma cell line PC12 has been extensively used as a model for the morphological changes that accompany both processes. When treated with nerve growth factor (NGF) for long periods (48-72 hr), PC12 cells extend neurites in a process analogous to differentiation of sympathetic neurons (Levi-Montalcini and Angeletti, 1968;Greene and Tischler, 1982;Vaudry et al., 2002). Conversely, when PC12 cells, plated on laminin-coated surfaces, are simultaneously stimulated with NGF and phorbol 12-myristate-13-acetate (PMA), the cell body recedes away from points of attachment to the plate surface, and the cells assume a crescent shape (Glowacka and Wagner, 1990). The latter phenomenon is rapid (observable within 1 hr of NGF + PMA addition) and has been considered a model for "fast neuronal migration."The signaling cascades that mediate the fast migration process have not been adequately described. Specifically, it is known that PMA exerts its effects via the activation of protein kinase C (PKC), which was independently shown to be essential for cell motility in primary (Choe et al., 2003). NGF has been shown to promote the survival and differentiation of multiple neuronal populations within the central nervous system (LeviMontalcini and Angeletti, 1968), but the signaling mechanisms involved in NGF-induced neuritogenesis remain controversial (Vaudry et al., 2002).We recently identified "soluble" adenylyl cyclase (sAC) as the source of cAMP downstream of NGF and a mediator of NGF-induced activation of the monomeric GTPase Rap1 in PC12 cells (Stessin et al., 2006). sAC is a ubiquitously expressed cAMP source in mammalian cells, distinct from the classically described trans-membrane adenylyl cyclases (tmACs) in its subcellular localization and biochemical profile. In this report, we demonstrate that the NGFsAC signaling axis is also required for fast migration. We also show that stimulation of PC12 cells with PMA results in cAMP elevation via tmACs, but, unlike sAC-generated cAMP, tmAC-generated cAMP does not contribute to the fast migration phenomenon. These results reveal the existence of distinct pools of cAMP, which are generated by independent sour...

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