Trends in pharmacological sciences
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Voltage-dependent Na+ channels in sensory nerves contribute to the control of membrane excitability and underlie action potential generation. Na+ channel subtypes exhibit a neurone-specific and developmentally regulated pattern of expression, and changes in both channel expression and function are caused by disease. ⋯ Insight into the role of Na(v)1.8 in pain pathways has been gained by the generation of a null mutant. Although drugs discriminate poorly between subtypes, the molecular diversity of channels and subtype-specific modulation might provide opportunities to target pain pathways selectively.
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Trends Pharmacol. Sci. · Aug 1999
ReviewSpinal systems and pain processing: development of novel analgesic drugs with mechanistically defined models.
Much research has been undertaken in the field of pain in an attempt to find an effective treatment. Insights into the underlying mechanisms of pain have been gained from studies using preclinical animal models (acute stimuli, post-tissue injury and peripheral nerve injury) and evaluating their similarity with the human condition. In this article, these pain models are summarized and the mechanisms of pain discussed in relation to spinal processing. In the context of this research the therapeutic potential of novel analgesics is highlighted as the future looks forward to the many possibilities that the targeted spinal delivery of drugs can bring.
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Trends Pharmacol. Sci. · Sep 1998
Modulation of opioid analgesia, tolerance and dependence by Gs-coupled, GM1 ganglioside-regulated opioid receptor functions.
Studies of direct excitatory effects elicited by opioid agonists on various types of neurone have been confirmed and expanded in numerous laboratories following the initial findings reviewed previously by Stanley Crain and Ke-Fei Shen. However, the critical role of the endogenous glycolipid GM1 ganglioside in regulating Gs-coupled, excitatory opioid receptor functions has not been addressed in any of the recent reviews of opioid stimulatory mechanisms. This article by Stanley Crain and Ke-Fei Shen focuses on crucial evidence that the concentration of GM1 in neurones might, indeed, play a significant role in the modulation of opioid receptor-mediated analgesia, tolerance and dependence.
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The importance of the inhibitory neurotransmitter, GABA, within higher centres of the mammalian brain is unquestionable. However, its role within the spinal cord is of equal significance. There have been numerous studies over the past two decades that have established GABA as a neurotransmitter at both post- and presynaptic sites in the cord. Here, Marzia Malcangio and Norman Bowery review the current status of GABA in relation to nociception and skeletal muscle tone, and indicate that its contribution to spinal cord function should not be overlooked.