European journal of pain : EJP
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We have recently reported that the spinal angiotensin (Ang) converting enzyme (ACE)/Ang II/AT1 receptor axis and downstream p38 MAPK phosphorylation are activated in streptozotocin (STZ)-induced diabetic mice and lead to tactile hypersensitivity. Moreover, our previous results suggested that the intrathecal (i.t.) administration of Ang (1-7), an N-terminal fragment of Ang II, may attenuate the Ang II-induced nociceptive behaviour through the inhibition of p38 MAPK phosphorylation via Mas receptors. Here, we investigated whether the i.t. administration of Ang (1-7) can attenuate STZ-induced diabetic neuropathic pain. ⋯ The ACE2/Ang (1-7)/Mas receptor axis was down-regulated in the spinal cord of STZ mice and the i.t. administration of Ang (1-7) attenuated the STZ-induced diabetic neuropathic pain via Mas receptors. Therefore, the activation of this axis could be an effective therapeutic target to alleviate the neuropathic pain in diabetic patients.
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Review
Mechanisms of spinal cord stimulation for the treatment of pain: Still in the dark after 50 years.
Despite the value of spinal cord stimulation (SCS) in treating some patients with focal neuropathic pain, technological advances in stimulator design and treatment protocols have not correlated with significant improvements in clinical outcomes. This may be because incomplete understanding of the mechanisms underlying SCS precludes improvement in clinical efficacy. In this brief review, we (a) review phenomenological effects of SCS, (b) review the literature on proposed spinal sites of action of SCS and (c) propose a novel hypothesis of mechanism of action. ⋯ We review possible spinal mechanisms of action of spinal cord stimulation for neuropathic pain, proposing that direct modulation of dorsal horn neurons is crucial. We suggest that mechanistic insights are needed for translation into more favourable clinical outcomes.
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Nociceptive pain remains a prevalent clinical problem and often poorly responsive to the currently available analgesics. Previous studies have shown that astroglial glutamate transporter-1 (GLT-1) in the hippocampus and anterior cingulate cortex (ACC) is critically involved in pain processing and modulation. However, the role of astroglial GLT-1 in nociceptive pain involving the hippocampus and ACC remains unknown. We investigated the role of 3-[[(2-Methylphenyl) methyl]thio]-6-(2-pyridinyl)-pyridazine (LDN-212320), a GLT-1 activator, in nociceptive pain model and hippocampal-dependent behavioural tasks in mice. ⋯ The present study provides new insights and evaluates the role of GLT-1 activator in the modulation of nociceptive pain involving hippocampus and ACC. Here, we provide evidence that GLT-1 activator could be a potential therapeutic utility for the treatment of nociceptive pain.
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Total intravenous anesthesia with propofol has been shown to reduce postoperative pain in some clinical studies, but knowledge of its underlying analgesic mechanism remains limited. In this study, we compared the analgesic effects of propofol versus isoflurane in an animal model of postoperative pain and evaluated its underlying molecular mechanisms. ⋯ These findings may provide a new mechanism for the postsurgical analgesic effect of propofol, which is particularly interesting during the subacute period after surgery as it is the critical period for the development of persistent postsurgical pain.