Spinal serum- and glucocorticoid-regulated kinase 1 (SGK1) signaling contributes to morphine-induced analgesic tolerance in rats
In this study, we determined whether spinal SGK1 signaling contributes to the development of morphine analgesic tolerance. Chronic morphine administration markedly induced phosphorylation of SGK1 in the spinal dorsal horn neurons. Intrathecal injection of SGK1 inhibitor GSK-650394 reduced the development of morphine tolerance with a significant leftward shift in morphine dose-effect curve. Furthermore, spinal inhibition of SGK1 suppressed morphine-induced phosphorylation of nuclear factor kappa B (NF-κB) p65 and upregulation of NMDAR NR1 and NR2B expression in the spinal dorsal horn. In contrast, intrathecal administration of NMDAR antagonist MK-801 had no effect on the phosphorylation of SGK1 in morphine-treated rats. In addition, morphine-induced upregulation of NR2B, but not NR1, was significantly abolished by intrathecal pretreatment with PDTC, a specific NF-κB activation inhibitor. Finally, spinal delivery of SGK1 small interfering RNA exhibited similar inhibitory effects on morphine-induced tolerance, phosphorylation of NF-κB p65, as well as upregulation of NR1 and NR2B expression. Our findings demonstrate that spinal SGK1 contributes to the development of morphine tolerance by enhancing NF-κB p65/NMDAR signaling. Interfering spinal SGK1 signaling pathway could be a potential strategy for prevention of morphine tolerance in chronic pain management.
Chronic low back pain (CLBP) is a condition that commonly consumes many resources and creates economic burden for the health care system. Evidence-informed care is crucial to guide management and prevent unnecessary procedures, including diagnostic imaging. Conservative therapy is currently recommended as the first-line and the most cost-effective treatment. Antibiotic therapy and surgical procedures are considered last resort treatment options for CLBP. The aim of this article is to summarize CLBP options for nurse practitioners (NP).
ConclusionsA robust body of evidence examining SCS and PNS was identified. Only one study for PNFS and TENS was identified; both reported pain reductions. Generally, neurostimulation improved pain control. Future studies should examine the effectiveness of neurostimulation offered early in the trajectory of chronic pain.
Conclusions: These findings indicated the crucial role of the P2Y6 receptor in modulating the microglial and inflammatory responses in the process of NP in vivo. Results from this study would provide insights into targeting the P2Y6 receptor to treat NP in the near future. PMID: 31281556 [PubMed - in process]
Conclusion: This case series was able to demonstrate that our described novel spinal cord stimulator trial lead placement and dressing technique can decrease the incidence of lead displacement and migration, thus improving trial success. PMID: 31281554 [PubMed - in process]
CONCLUSIONS: A combination of SDT with CSE has proven to be more significant when compared with CSE alone to reduce pain and disability in subjects with chronic LDP. PMID: 31282394 [PubMed - as supplied by publisher]
For more than a century, clinicians have noticed a paradoxical phenomenon: certain patients who are taking opioids (which are supposed to numb pain) become more sensitive to pain than those who are not taking opioids. The earliest observation of this phenomenon can be traced back to the British physician Sir Clifford Allbutt, who, in 1870, described it: “at such times I have certainly felt it a great responsibility to say that pain, which I know is an evil, is less injurious than morphia, which may be an evil. Does morphia tend to encourage the very pain it pretends to relieve?” Research studies and clinical ob...
AbstractPurpose of ReviewThe purpose of this study is to evaluate the effectiveness of a multimodal approach to treating chronic low back pain.Recent FindingsChronic non-cancer-related back pain is often a frustrating and poorly managed problem for patients. It poses a significant public health issue worsened by the widespread use of narcotics. In 2016, the CDC released guidelines with noticeably more strict recommendations on prescription of narcotics for pain.SummaryVeterans at an interventional pain clinic presenting with chronic back pain refractory to medical and to surgical care were enrolled in an 8-week interdiscip...
Gluten? Lactose? Stomach pain? Digestive troubles? Way too many people suffer from gastrointestinal issues, and much less are aware of the digital technologies that can come to their aid. Did you know that digestibles could successfully replace the dreaded colonoscopy? Or have you heard about microbiome testing? What about the swarm of health apps supporting dietary restrictions? We took a deep breath and jumped into the universe of digital technologies just to bring you as much information about the future of gastroenterology as possible. Will you jump after us? IBS, colorectal cancer, and other animals Referring to...
Discussion: The current case series describes the use of a targeted exercise approach consisting mostly of hip abductor strengthening in a group of patients with CLBP and hip abductor weakness. The results indicated that this approach may be effective in reducing pain and improving function, particularly for older patients.
Conclusion: This review will offer clinical evidence of acupuncture injection therapy for the patients with nonspecific CLBP. PROSPERO Research registration identifying number: CRD42019119158