Articles: neuropathic-pain.
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Neuroscience letters · Oct 2014
Spinal cord stimulation exerts analgesia effects in chronic constriction injury rats via suppression of the TLR4/NF-κB pathway.
Spinal cord stimulation (SCS) is an established method for treating chronic neuropathic pain. However, the mechanisms underlying the pain relieving effect of SCS on neuropathic pain remain unclear. Evidence shows that the toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signal transduction pathway plays a key role in chronic neuropathic pain. ⋯ Compared with the control group, the CCI rats displayed a significantly decreased MWT. After SCS for 3 days, the expression of TLR4/NF-κB and the levels of interleukin(IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the spinal cord were lower in the SCS group compared to those in the CCI and sham spinal cord stimulation (S-SCS) groups. These results indicate that SCS could effectively attenuate neuropathic pain in CCI rats by inhibiting the activation of the TLR4/NF-κB signaling pathway and by inhibiting the up-regulation of pro-inflammatory cytokines in the spinal cord.
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Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in the development of chronic pain, but the complex regulation of STAT3-dependent pathway and the functional significance of inhibiting this pathway during the development of neuropathic pain remain elusive. To evaluate the contribution of the JAK2/STAT3 pathway to neuropathic pain and the potentiality of this pathway as a novel therapeutic target, we examined the effects of the STAT3 inhibitor WP1066 by intrathecal administration in a rat model of bilateral chronic constriction injury (bCCI). The pain behavior tests were performed before the surgery and on postoperative day 3, 7, 14 and 21. ⋯ Our results found that the JAK2/STAT3 pathway in the spinal cord dorsal horn was significantly activated in the bCCI neuropathic pain rats. WP1066, which inhibited the STAT3 pathway specifically, could partially alleviate the pain behavior of the bCCI rats. So it may serve as a novel therapeutic strategy against neuropathic pain.
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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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Background and aims We have previously reported that systemic administration of sinomenine produced antinociception in various experimental pain conditions in rodents, particularly in models of neuropathic pain. In the present study we assessed the effects of repeated administration of sinomenine in two rodent models of neuropathic pain in order to study the development of tolerance. Methods The analgesic effect of sinomenine was tested in female Sprague-Dawley rats that exhibited mechanical and cold hypersensitivity following ischaemic injury to the spinal cord and in male C57/BL6 mice that developed mechanical hypersensitivity after ischaemic injury to the sciatic nerve. ⋯ The effect of sinomenine on response threshold persisted for days after termination of the 5 day drug administration. Conclusions The results suggest that repeated administration of simomenine produced an enhanced anti-allodynic effect without tolerance in rodent models of neuropathic pain. Implications Sinomenine may be tested as a novel analgesic in treating some forms of chronic neuropathic pain in patients.