Current pharmaceutical design
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The treatment of chronic pain arising from deep tissues is currently inadequate and there is need for new pharmacological agents to provide analgesia. The endogenous paracrine hormone/neurotransmitter oxytocin is intimately involved in the modulation of multiple physiological and psychological functions. ⋯ The present article reviews the existent human and basic science data related to the direct and indirect effects of oxytocin on pain. Due to its analgesic, anxiolytic, antidepressant and other central nervous system effects, there is strong evidence that oxytocin and other drugs acting through the oxytocin receptor could act as multifunctional analgesics with unique therapeutic value.
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Diabetic macular edema (DME) represents the most common cause of vision loss in patients affected by diabetes mellitus. Although the pathophysiology of DME is not wholly understood, vascular endothelial growth factor (VEGF) has been identified as a key contributor to the development of DME. ⋯ In particular, VEGF-inhibitors that have been studied for diabetic retinopathy include pegaptanib, ranibizumab, bevacizumab, and aflibercept. The present review analyzes the main characteristics of each molecule, describing the most important results of clinical trails.
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Neuronal injury not only results in severe alteration in the function of primary sensory neurons and their central projection pathway, but is also associated with a robust immune response at almost every level of the somatosensory system. Evidence from animal studies suggests undoubtedly that bi-directional signalling between the immune system and the nervous system contribute to the development and maintenance of chronic neuropathic pain. Non-neuronal cells, including peripheral immune cells, CNS/PNS glial cells and endothelial cells play important roles in the neuroimmune interaction and subsequent persistent hypersensitivity. ⋯ Therapeutic agents targeting inflammation provide an exciting prospect. Yet, considering the heterogeneous conditions presented in neuropathic pain, no matter the etiologies, or the pathophysiology during different stages of the disease; and the complexity of the immune response to the damage on the nervous system, it appears that finely tuned strategies of modulating inflammation are essential to warrant an effective treatment for neuropathic pain. We want to reduce pain; we also want to promote tissue repair and functional recovery.
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A robust circadian timekeeping system is important for human health and well-being. Inappropriately timed light exposure can cause circadian and sleep disruption, which has been shown to have negative health consequences. ⋯ Cycled lighting and increased exposure to sunlight in medical care facilities have been shown to have positive effects on patient recovery and well-being, and expedite hospital discharge. Additional clinical research is needed to determine the optimal light exposure timing, duration, intensity, and spectrum to best promote recovery, health and well-being in the context of medical care.
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Neuropathic pain is characterized by complicated combination of positive (e.g., hyperalgesia and allodynia) and negative (e.g., hypoesthesia and hypoalgesia) symptoms, and is often refractory to conventional pharmacological agents, including morphine. Although the molecular mechanisms for positive symptoms are extensively studied, those for negative symptoms are poorly understood. There is convincing evidence that altered gene expression within peripheral and central nervous systems is a key mechanism for neuropathic pain; however, its transcriptional mechanisms are poorly understood. ⋯ Importantly, there is emerging evidence that a variety of genes undergo epigenetic regulation via DNA methylation and histone modifications within peripheral and central nervous systems, thereby contributing to the alterations in both pain sensitivity and pharmacological efficacy in neuropathic pain. In this review, we will highlight the epigenetic gene regulation underlying neuropathic pain, especially focusing on the negative symptoms. Moreover, we will discuss whether epigenetic mechanisms can serve as a potential target to treat neuropathic pain.