The lateral hypothalamus (LH) sends a dense glutamatergic and peptidergic projection to dopamine neurons in the ventral tegmental area (VTA), a cell group known to promote reinforcement and aspects of reward. The role of the LH to VTA projection in reward-seeking behavior can be informed by using optogenetic techniques to dissociate the actions of LH neurons from those of other descending forebrain inputs to the VTA. In the present study, we identify the effect of neurotensin (NT), one of the most abundant peptides in the LH to VTA projection, on excitatory synaptic transmission in the VTA and reward-seeking behavior. Mice displayed robust intracranial self-stimulation of LH to VTA fibers, an operant behavior mediated by NT 1 receptors (Nts1) and NMDA receptors. Whole-cell patch-clamp recordings of VTA dopamine neurons demonstrated that NT (10 nM) potentiated NMDA-mediated EPSCs via Nts1. Results suggest that NT release from the LH into the VTA activates Nts1, thereby potentiating NMDA-mediated EPSCs and promoting reward. The striking behavioral and electrophysiological effects of NT and glutamate highlight the LH to VTA pathway as an important component of reward.

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Central post-stroke pain (CPSP) is still an underestimated complication of stroke, resulting in impaired quality of life and, in addition to the functional and cognitive consequences of stroke, the presence of CPSP may be associated with mood disorders, such as depression, anxiety, and sleep disturbances. This type of pain may also impair activities of daily living and further worsen quality of life, negatively influencing the rehabilitation process. The prevalence of CSPS in the literature is highly variable (1%–12%) according to different studies, and this variability could be influenced by selection criteria and the different ethnic populations being investigated. With this scenario in mind, we performed a population-based study to assess the prevalence of CPSP and its main features in a homogeneous health district (Rimini, Italy), including five hospitals for a total population of 329,970 inhabitants. From 2008 to 2010, we selected 1,494 post-stroke patients and were able to interview 660 patients, 66 (11%) of whom reported pain with related tactile and thermal hyperesthesia, accompanied by needle puncture, tingling, swelling, and pressure sensations. Patients reported motor impairment and disability, which influenced their working ability, rehabilitation, and social life. Despite this severe pain state, there was a high percentage of patients who did not receive adequate treatment for pain.

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More than 50% of cancer patients do not undergo adequate pain treatment (6). The pain prevents patients from carrying out normal daily activities and influences appetite, mood, self-esteem, relationships with others and mobility. In some countries it is seen that untreated pain leads to a desire for death, euthanasia or assisted suicide (4). Pain relief improves the quality of life (7). Unfortunately, cancer pain is often not treated or is treated inadequately. The WHO have demonstrated that most, if not all, cases of cancer pain, could be treated successfully, if existing medical knowledge and suitable therapies were put into practice. There exists a lacuna in the treatment that is represented by the difference between what could be done and what is actually done in the fight against cancer pain. Training, informing health workers and facilitating access to analgesic treatments and palliative care can close this gap (5). The WHO Expert Committee on Cancer Pain Relief and Active Supportive Care (8), stated in 1990 that "freedom from pain should be considered a right of every cancer patient and access to pain therapy as a measure of respect for this right". In 1986, the World Health Organization, in an effort to optimize cancer pain therapy, suggested a simple three point analgesic ladder (figure 1) for the use of opioids for the treatment of cancer pain (6). Although adoption of the therapies suggested by this analgesic ladder improves pain management in the majority of patients, it is estimated that from 5% to 15% of patients with cancer pain are unable to adequately control their pain, following these guidelines (9-11). In addition there are pains classified as "breakthrough pains" (12) which are difficult to manage www.intechopen.com Intrathecal Drug Administration for the Treatment of Cancer and Non-Cancer Chronic Pain 113 and contain, both because they are unpredictable and because there is a lack of suitable drugs. In order to tackle this need, new drug formulations have been developed such as immediate release morphine, transmucosal fentanyl (13) and indications for invasive treatments with analgesic infusion in the liquor.