Inhibition of spinal 15-LOX-1 attenuates TLR4-dependent, nonsteroidal anti-inflammatory drug–unresponsive hyperalgesia in male rats

Although nonsteroidal anti-inflammatory drugs are the first line of therapeutics for the treatment of mild to moderate somatic pain, they are not generally considered to be effective for neuropathic pain. In the current study, direct activation of spinal Toll-like 4 receptors (TLR4) by the intrathecal (IT) administration of KDO2 lipid A (KLA), the active component of lipopolysaccharide, elicits a robust tactile allodynia that is unresponsive to cyclooxygenase inhibition, despite elevated expression of cyclooxygenase metabolites in the spinal cord. Intrathecal KLA increases 12-lipoxygenase-mediated hepoxilin production in the lumbar spinal cord, concurrent with expression of the tactile allodynia. The TLR4-induced hepoxilin production was also observed in primary spinal microglia, but not in astrocytes, and was accompanied by increased microglial expression of the 12/15-lipoxygenase enzyme 15-LOX-1. Intrathecal KLA-induced tactile allodynia was completely prevented by spinal pretreatment with the 12/15-lipoxygenase inhibitor CDC or a selective antibody targeting rat 15-LOX-1. Similarly, pretreatment with the selective inhibitors ML127 or ML351 both reduced activity of the rat homolog of 15-LOX-1 heterologously expressed in HEK-293T cells and completely abrogated nonsteroidal anti-inflammatory drug–unresponsive allodynia in vivo after IT KLA. Finally, spinal 12/15-lipoxygenase inhibition by nordihydroguaiaretic acid (NDGA) both prevents phase II formalin flinching and rev...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

Related Links:

Abstract The Editor-in-Chief has retracted this article [1] because an investigation by Keio University has concluded that there are inaccuracies in the data reported. PMID: 31730223 [PubMed - in process]
Source: Aging Clinical and Experimental Research - Category: Geriatrics Authors: Tags: Aging Clin Exp Res Source Type: research
ConclusionUsing the data from this study, it was possible to calculate the odds ratio of the agricultural pilot suffering low back pain, based on eight personal and work-related factors.Relevance for the industryBased on the results of the present study, it was possible to define strategies to reduce whole-body exposure in agricultural aircraft and, consequently, improve the pilots’ health. Strategies included management of the exposure and aircraft improvement.Graphical abstract
Source: International Journal of Industrial Ergonomics - Category: Occupational Health Source Type: research
Enhanced recovery after surgery is an interdisciplinary, multimodal approach to improve postoperative outcomes by applying multiple evidenced-based interventions. It has been adapted at multiple institutions for patients undergoing spine surgery to combat the rising rate of opioid consumption. Various preoperative, intraoperative, and postoperative pharmacologic and nonpharmacologic interventions have been introduced to augment patient care with the goal to decrease hospital length of stay and improve postoperative outcomes. Future studies will focus on health care-related quality of life outcomes to evaluate the effective...
Source: Neurosurgery Clinics of North America - Category: Neurosurgery Authors: Source Type: research
This study protocol describes the process undertaken by the research team to design the methodology of this study.MethodsParticipants aged between 18 and 64 years, injured in a crash involving a motorised vehicle, will be recruited from public hospitals in Queensland. Participants will be excluded if their injuries are severe, including severe traumatic brain injury or spinal cord injury. Baseline data collection will occur within 28 days of the injury, with major follow up assessments occurring at 6 and 12 months post-baseline. Outcome measures include return to work status, health-related quality of life, musculoskeletal...
Source: Journal of Transport and Health - Category: Occupational Health Source Type: research
In this study, the authors described the technical notes of percutaneous transforaminal endoscopic lumbar discectomy (PTELD) through unilateral approach and compared PTELD through unilateral versus bilateral approach for L3/4 or L4/5 lumbar disc herniation with bilateral symptoms.MethodsA prospective randomized clinical study was performed from June 2014 to October 2016. A total of 71 patients with lumbar disc herniation (L3/4 or L4/5) and bilateral symptoms were divided randomly into Unilateral-Approach group (n = 35) or Bilateral-Approach group (n = 36). Operation time, blood loss, intraoperat...
Source: European Spine Journal - Category: Orthopaedics Source Type: research
Authors: Hay ME, Connelly DM Abstract Physical inactivity and chronic back pain are prevalent among older adults; however, there are individuals who persist in exercising despite daily pain. This research explored the meaning of exercise in the lives of older adults with chronic back pain. Hermeneutic phenomenology, valuing everyday experiences and highlighting meaning, was employed. Individual in-depth interviews with 10 adults aged 65 years and older gathered rich descriptions of their experiences. Data collection and analyses were iterative processes. The experience of exercise was inextricably connected with ol...
Source: Journal of Aging and Physical Activity - Category: Geriatrics Tags: J Aging Phys Act Source Type: research
CONCLUSION: Men with rectal prolapse were younger, healthier, and had relatively better anorectal function than women. The Delorme-Thiersch operation in men promoted lower recurrence rates and was advantageous in preserving the fertility of young patients, but the incidence of complications was also higher in men. Adequate counseling and preparation for the possibility of complications are needed. PMID: 31726002 [PubMed]
Source: Annals of Coloproctology - Category: Gastroenterology Tags: Ann Coloproctol Source Type: research
By Irene Mirembe, Knowledge management manager, IntraHealth International The BABIES matrix is a simplified quality-improvement methodology for collecting and displaying data. It was introduced and implemented by the Katakwi Hospital to improve services. Photo courtesy of Irene Mirembe.November 15, 2019Margret Imma from Uganda’s Katakwi District looks lovingly at her 4-month-old, bubbly baby boy, Orisa. He is glowing and Margret couldn’t be happier. This was not the case a few months ago, when Orisa was born too soon.“The pain and suffering that came with handling a preterm baby was unbearable,”...
Source: IntraHealth International - Category: International Medicine & Public Health Authors: Tags: Maternal, Newborn, & Child Health Education Performance Midwives Source Type: news
What is the Definition of “Opioid”? The definition of opioid is as follows: Opioids are a class of drugs that include the illegal drug heroin, synthetic opioids such as fentanyl, and pain relievers available legally by prescription, such as oxycodone, hydrocodone, codeine, morphine, and many others. Opioids work by interacting with the opioid receptors on nerve cells in the body and brain. By interacting with these receptors, opioids medications are able to cut off communication between the pain point on the body to the brain. This chemical interaction gives it’s users pain relief that is too great for ov...
Source: Cliffside Malibu - Category: Addiction Authors: Tags: Addiction to Pharmaceuticals fentanyl heroin heroin addiction opiate opiate abuse opiate addiction opiates opioid opioids Source Type: blogs
Condition:   Low Back Pain Interventions:   Behavioral: Qigong Exercise;   Behavioral: P.Volve Exercises Sponsor:   University of Minnesota Recruiting
Source: - Category: Research Source Type: clinical trials
More News: Anesthesiology | Back Pain | Brain | Neurology | Pain | Study