| 1. |
- Lind, Anne-Li, et al.
(författare)
-
A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients
- 2016
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:2
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.
|
|
| 2. |
- Lind, Anne-Li, et al.
(författare)
-
Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients : A Proteomic Mass Spectrometric Analysis
- 2016
-
Ingår i: Neuromodulation. - : Elsevier BV. - 1094-7159 .- 1525-1403. ; 19:6, s. 549-562
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesElectrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. MethodsTwo different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks. ResultsEighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3). ConclusionPreviously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain.
|
|
| 3. |
- Ljungvall, Hanna, et al.
(författare)
-
“Opioids are opioids” – a phenomenographic analyses of physicians’ understanding of what makes the initial prescription of opioids become long-term opioid therapy
- 2022
-
Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 22:3
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective: To explore prescribers’ understanding of what makes initial prescription of opioids become long-term-opioid therapy (opioids >90 days).Design: Qualitative study, using phenomenography for data analysis.Methods: Semi-structured interviews conducted by one researcher were used for data collection. Participants were recruited consecutively until categorical saturation was reached. The transcripts were analyzed and categorized by two researchers. A third researcher checked for consistency between the data and the categories. An outcome space was constructed representing the logical relationship between the categories.Setting: Primary, secondary and tertiary care in Sweden.Subjects: Fifteen attending physicians working within the fields of general practice, rehab medicine, orthopedic surgery, neurosurgery, or obstetrics and gynecology.Results: The analysis identified six categories: The addictive opioid, The deserving patient, The ignorant prescriber, The lost patient, The compassionate prescriber, and The exposed prescriber. The differences in conceptions among the categories were clarified through three main contributors related to opioid therapy: prescriber’s characteristics, patient’s characteristics, and the healthcare organization.Conclusion: Opioids were understood as being addictive with long-term use promoting a downward spiral of tolerance and withdrawal driving the pain, leading to continued prescription. Long-term opioid therapy could be justified for patients who improved in function, and who were perceived as trustworthy. Inadequate follow-up of patients, poor training in pain management and addiction medicine, personal attitudes and beliefs about opioids, a perceived professional obligation to treat patients with pain, and lack of collegial support, were factors understood to promote clinically unindicated long-term opioid therapy.
|
|
| 4. |
- Memedi, Mevludin, PhD, 1983-, et al.
(författare)
-
Sensor-based Measurement of Nociceptive Pain : An Exploratory Study with Healthy Subjects
- 2022
-
Ingår i: Pervasive Computing Technologies for Healthcare. - Cham : Springer. - 9783030991937 - 9783030991944 ; , s. 88-95
-
Konferensbidrag (refereegranskat)abstract
- Valid assessment of pain is essential in daily clinical practice to enhance the quality of care for the patients and to avoid the risk of addiction to strong analgesics. The aim of this paper is to find a method for objective and quantitative evaluation of pain using multiple physiological markers. Data was obtained from healthy volunteers exposed to thermal and ischemic stimuli. Twelve subjects were recruited and their physiological data including skin conductance, heart rate, and skin temperature were collected via a wrist-worn sensor together with their selfreported pain on a visual analogue scale (VAS). Statistically significant differences (p< 0.01) were found between physiological scores obtained with the wearable sensor before and during the thermal test. Test-retest reliability of sensor-based measures was good during the thermal test with intraclass correlation coefficients ranging from 0.22 to 0.89. These results support the idea that a multi-sensor wearable device can objectively measure physiological reactions in the subjects due to experimentally induced pain, which could be used for daily clinical practice and as an endpoint in clinical studies. Nevertheless, the results indicate a need for further investigation of the method in real-life pain settings.
|
|
| 5. |
- Nylander, Erik, 1986-, et al.
(författare)
-
Mitochondrial function and membrane integrity: an in vitro comparison between six commonly used opioids
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: There is an ongoing opioid crisis in the United States where the illicit and non-medical use of prescription opioids is associated with an increasing number of overdose deaths. Few studies have investigated the effects of opioid-induced effects on cell viability, and comparative studies are scarce. Here we examine the toxic effect on cell viability from six commonly used opioids; methadone, morphine, oxycodone, hydromorphone, ketobemidone, and fentanyl with respect to mitochondrial and membrane function in vitro. Methods: The opioids were tested in four different cell cultures; primary cortical cell cultures, human neuroblastoma SH-SY5Y cells, and both differentiated and undifferentiated neuroblastoma/glioma hybrid NG108-15 cells. Results: The six different opioids displayed the same trend of reduced cell viability in all four cell cultures. The ranking of opioids, with respect to reduced cell viability were as follows; methadone, fentanyl, ketobemidone, oxycodone, hydromorphone, and morphine. Conclusion: Methadone was ranked as the most toxic opioid closely followed by fentanyl. Ketobemidone and oxycodone had modest effects while both hydromorphone and morphine only displayed little to no negative impact on cell viability.
|
|
| 6. |
- Sjödin, Marcus O.D. 1978-, et al.
(författare)
-
Proteomic analysis of cerebrospinal fluid from neuropathic pain patients reveals proteins with potential role in spinal cord stimulation
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Spinal cord stimulation (SCS) is a widely used mode of therapy in neuropathic pain of peripheral origin. Despite its well-established clinical use, the underlying physiological mechanisms behind the beneficial analgesic effects of SCS still remain only partially known. In this study, a proteomic approach was used to compare the protein concentration in cerebrospinal fluid (CSF) from responsive human patients (n=12). The comparison was made between samples taken during at two different timepoints. The first sample was taken when the stimulator had been off for 48 h, the second sample was taken after the stimulator had been used for three weeks. In total, 419 proteins could be identified (P<0.05) and relatively quantified using a shotgun proteomic approach based on immunoaffinity fractionation, multiplexed dimethyl labeling and reversed phase nanoliquid chromatography in combination with electrospray ionization high resolution tandem mass spectrometry. Statistical analysis (P<0.01) revealed two significantly down-regulated proteins; Co2 (P=0.0046), Ibp6 (P=0.0071) and five up-regulated proteins; Lynx1 (P=0.000048), Klk6 (P=0.00058), Angt (P=0.00057), A4 (P=0.0052) and Sap3 (P=0.0076) during the on state. Lynx1was the most significantly and consistently increased protein in all patients. Lynx1 is a modulator of the nicotinic acetylcholine receptor activity in the central nervous system previously described in mice. This study reports for the first time the possible involvement of Lynx1 in SCS-induced analgesia in humans.
|
|
