Articles: neuropathic-pain.
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Recent studies have revealed the antinociceptive effects of glycine transporter (GlyT) inhibitors in neuropathic pain models such as sciatic nerve-injured and diabetic animals. Bone cancer can cause the most severe pain according to complex mechanisms in which a neuropathic element is included. Bone cancer modifies the analgesic action of opioids and limits their effectiveness, and thus novel medicament for bone cancer pain is desired. ⋯ GlyT inhibitors with or without morphine may be a new strategy for the treatment of bone cancer pain and lead to further investigations of the mechanisms underlying the development of bone cancer pain.
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Expert Opin Investig Drugs · Oct 2014
Review Comparative StudyZucapsaicin for the treatment of neuropathic pain.
Neuropathic pain (NP) is a chronic disease that stems from a primary lesion or dysfunction of the central or peripheral nervous system. Zucapsaicin is a synthetic cis isomer of natural capsaicin that has shown therapeutic efficacy in pain accompanying osteoarthritis of the knee. It is also currently under investigation for the relief of severe pain in adults suffering from NP. ⋯ The mechanism of action and clinical indications of zucapsaicin are similar to that of its naturally occurring isomer, capsaicin. However, in contrast to capsaicin, zucapsaicin is better tolerated. In the future, zucapsaicin could become a valuable drug for treating pain relief. Indeed, it is possible, in addition to providing NP relief, that it may have a use in treating osteoarthritic pain, headaches and pain that accompany intestinal diseases.
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Spinal cord stimulation (SCS) is well accepted for the treatment of chronic pain since its beginning in 1967. As its use continues to enter into the chronic pain treatment algorithm earlier, conscience patient selection and durability of the therapy are clearly clinically relevant. To improve treatment efficacy, consensus statements and guidelines were developed. ⋯ The current available guideline statements have clear deficiencies in either scope of coverage, evidence synthesis, or lack of transparency of funding. Improved evidence and best practice/guideline assessment may improve patient outcomes and accessibility to these important modalities. Further prospective comparator randomized data are required to not only provide data of clinical and cost-effectiveness in other indications but also to better describe the position of neurostimulation application within the disease management pathway. Therein cases where there appears to be sufficient evidence and consensus, every effort should be made to secure access to these effective therapies. Importantly, each guideline only has a useful clinical half-life, if not updated. This should be acknowledged by both clinicians and third-party payers. Based on these deficiencies, the International Neuromodulation Society recommended the creation of a consensus conference to examine the appropriate use of neurostimulation for pain and ischemic disease.
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Pannexin 1 (panx1) is a large-pore membrane channel expressed in many tissues of mammals, including neurons and glial cells. Panx1 channels are highly permeable to calcium and adenosine triphosphatase (ATP); on the other hand, they can be opened by ATP and glutamate, two crucial molecules for acute and chronic pain signaling in the spinal cord dorsal horn, thus suggesting that panx1 could be a key component for the generation of central sensitization during persistent pain. In this study, we examined the effect of three panx1 blockers, namely, 10panx peptide, carbenoxolone, and probenecid, on C-reflex wind-up activity and mechanical nociceptive behavior in a spared nerve injury neuropathic rat model involving sural nerve transection. ⋯ Intrathecal administration of the panx1 blockers significantly depressed the spinal C-reflex wind-up activity in both neuropathic and sham control rats, and decreased mechanical hyperalgesia in neuropathic rats without affecting the nociceptive threshold in sham animals. Western blotting showed that panx1 was similarly expressed in the dorsal horn of lumbar spinal cord from neuropathic and sham rats. The present results constitute the first evidence that panx1 channels play a significant role in the mechanisms underlying central sensitization in neuropathic pain.
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Brain Behav. Immun. · Oct 2014
Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling.
Patients suffering from neuropathic pain have a higher incidence of mood disorders such as depression. Increased expression of tumor necrosis factor (TNF) has been reported in neuropathic pain and depressive-like conditions and most of the pro-inflammatory effects of TNF are mediated by the TNF receptor 1 (TNFR1). Here we sought to investigate: (1) the occurrence of depressive-like behavior in chronic neuropathic pain and the associated forms of hippocampal plasticity, and (2) the involvement of TNFR1-mediated TNF signaling as a possible regulator of such events. ⋯ The onset of depressive-like behavior also coincided with increased hippocampal levels of TNF, and decreased expression of TNF receptor 2 (TNFR2), which were all fully restored after mice spontaneously recovered from pain. Notably, TNFR1(-/-) mice did not develop depressive-like symptoms after injury, nor were there changes in hippocampal neurogenesis and plasticity. Our data show that neuropathic pain induces a cluster of depressive-like symptoms and profound hippocampal plasticity that are dependent on TNF signaling through TNFR1.