Browse by Audience
Complex regional pain syndrome (CRPS) is related to microcirculation impairment caused by tissue hypoxia and peripheral cytokine overproduction in the affected human limb and chronic post-ischemic pain (CPIP) is considered as an animal model for this intractable disease. Previous studies suggest that the pathogenesis of CPIP involves the hypoxia inducible factor-1α (HIF-1α) and an exaggerated regional inflammatory and free radical response. The inhibition of HIF-1α is known to relieve CPIP. So, propofol, as a free radical scavenger, is very likely to be beneficial in terms of relieving CPIP.
Learn More >Medication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications. In previous proteomic studies, several proteins have been found at high concentrations in the urine of MOH patients and in the serum of rats with neuropathic pain. The aim of this study was to compare the serum levels of lipocalin-type Prostaglandin D2 synthase (L-PGDS), Vitamin D-binding protein (VDBP), apolipoprotein E (APOE) and apolipoprotein A1 (APOA1) in MOH patients and healthy individuals, further exploring their relationship with cutaneous pain thresholds (CPTs) in the territories innervated by the trigeminal nerve.
Learn More >α-Conotoxin Vc1.1 inhibits the nicotinic acetylcholine receptor (nAChR) α9α10 subtype and has the potential to treat neuropathic chronic pain. To date, the crystal structure of Vc1.1 bound-α9α10 nAChR remains unavailable, thus understanding the structure-activity relationship of Vc1.1 with the α9α10 nAChR remains challenging. In this study, the Vc1.1 side chains were minimally modified to avoid introducing large local conformation perturbation to the interactions between Vc1.1 and α9α10 nAChR. The results suggest that the hydroxyl group of Vc1.1 Y10 forms hydrogen bond with the carbonyl group of α9 N107 and a hydrogen bond donor is required, whereas Vc1.1 S4 is adjacent to the α9 D166 and D169, and a positive charge residue at this position increases the binding affinity of Vc1.1. Furthermore, the carboxyl group of Vc1.1 D11 forms two hydrogen bonds with α9 N154 and R81 respectively, whereas introducing an extra carboxyl group at this position significantly decreases the potency of Vc1.1. Second generation mutants of Vc1.1 [S4Dab, N9A] and [S4Dab, N9W] increased potency at the α9α10 nAChR by 20-fold compared with that of Vc1.1. The [S4Dab, N9W] mutational effects at positions 4 and 9 of Vc1.1 are not cumulative but are coupled with each other. Overall, our findings provide valuable insights into the structure-activity relationship of Vc1.1 with the α9α10 nAChR and will contribute to further development of more potent and specific Vc1.1 analogues.
Learn More >Antineoplastic drugs induce dramatic transcriptional changes in dorsal root ganglion (DRG) neurons, which may contribute to chemotherapy-induced neuropathic pain. K 1.1 controls neuronal excitability by setting the resting membrane potential. Here, we report that systemic injection of the chemotherapy agent paclitaxel time-dependently downregulates the expression of K 1.1 mRNA and its coding K 1.1 protein in the DRG neurons. Rescuing this downregulation mitigates the development and maintenance of paclitaxel-induced mechanical allodynia and heat hyperalgesia. Conversely, in the absence of paclitaxel administration, mimicking this downregulation decreases outward potassium current and increases excitability in the DRG neurons, leading to the enhanced responses to mechanical and heat stimuli. Mechanically, the downregulation of DRG K 1.1 mRNA is attributed to paclitaxel-induced increase in DRG DNMT3a, as blocking this increase reverses the paclitaxel-induced the decrease of DRG K 1.1 and mimicking this increase reduces DRG K 1.1 expression. In addition, paclitaxel injection increases the binding of DNMT3a to the K 1.1 gene promoter region and elevates the level of DNA methylation within this region in the DRG. These findings suggest that DNMT3a-triggered downregulation of DRG K 1.1 may contribute to chemotherapy-induced neuropathic pain. This article is protected by copyright. All rights reserved.
Learn More >Neuropathic pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite decades of research, it remains difficult to treat neuropathic pain. Lacosamide is a sodium-channel blocker that is efficacious in animal models of neuropathic pain. In humans, its effect in neuropathic pain is inconclusive, based on inconsistent results and very large placebo responses. Previous trials have not used patient stratification or looked for predictors for response.
Learn More >Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health – Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. We considered a 25% decrease of NIH-CPSI baseline score or a six-point reduction as MCID.
Learn More >In humans, pain due to osteoarthritis has been demonstrated to be associated with insomnia and sleep disturbances that affect perception of pain, productivity, and quality of life. Dogs, which develop spontaneous osteoarthritis and represent an increasingly used model for human osteoarthritis, would be expected to show similar sleep disturbances. Further, these sleep disturbances should be mitigated by analgesic therapy. Previous efforts to quantify sleep in osteoarthritic dogs using accelerometry have not demonstrated a beneficial effect of analgesic therapy; this is despite owner-reported improvements in dogs' sleep quality. However, analytic techniques for time-series accelerometry data have advanced with the development of functional linear modeling. Our aim was to apply functional linear modeling to accelerometry data from osteoarthritic dogs participating in a cross-over non-steroidal anti-inflammatory (meloxicam) drug trial. Significant differences in activity patterns were seen dogs receiving drug (meloxicam) vs. placebo, suggestive of improved nighttime resting (sleep) and increased daytime activity. These results align with owner-reported outcome assessments of sleep quality and further support dogs as an important translational model with benefits for both veterinary and human health.
Learn More >There are conflicting results about sex differences in the response to opioids for pain control and the role of potential influencing factors of these differences has not been investigated. We meta-analyzed differences and similarities between men and women in opioid response for pain control and investigated the potential influence of baseline pain intensity, age, body weight, and other factors in these findings. PubMed, Scopus, and Cochrane CENTRAL were searched through January 15, 2019, for clinical studies in which opioids were administered for pain control. We included clinical studies in which (a) opioids were used to treat acute or chronic pain, (b) the response to opioids was broken down for men and women, and (c) the response to opioids was reported as (i) difference between baseline and final Visual Analog Scale of Pain Intensity (VASPI) score 30 minutes after opioid administration (Delta-VASPI at 30'), or daily dose of opioids (ii) self-administered by patients (patient-controlled analgesia PCA), or (iii) administered by physicians. Risk of bias was evaluated using ROBINS-I and the overall quality of evidence for primary outcomes was evaluated using the GRADE system. Globally, we included 40 comparisons (6,794 patients). Regarding acute pain, we found moderate quality of evidence that women and men do not differ in their response to opioids 30 minutes after their administration [Delta-VASPI at 30': mean difference, MD = 0.42 (-0.07; 0.91)]. We also found moderate quality of evidence that women self-administer lower daily amounts of opioids [daily PCA: standardized mean difference, SMD = -0.30 (-0.41; -0.18)]. Regarding chronic pain, we found low quality of evidence that women receive lower daily doses for non-cancer pain [MD = -36.42 (-57.86; -14.99)]. By contrast, we found very low quality of evidence that women and men do not differ in the daily dose of opioids for cancer pain [MD = -16.09 (-40.13; 7.94)]. Age, comorbid mental disorders, type of administration, type of opioids, type of patients, and body weight significantly modified these results. In conclusion, the results of the present meta-analysis suggest that men and women may differ in the response to opioids for pain relief, but these differences as well as similarities are significantly influenced by factors like age and comorbid mental disorders. However, the role of these factors is not usually evaluated in the prescription of opioids for pain control. There is an urgent need to conduct clinical trials on the use of opioid medications for pain, in which information about all possible influencing factors are provided and broken down for men and women.
Learn More >The greatest increases in long-term opioid use and opioid-related overdose mortality in recent years have been among women in midlife. Common menopausal symptoms broadly affect health and health care utilization in midlife, but their contribution to chronic pain management during this period is unknown.
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) is a common and distressing side-effect of many chemotherapy regimens. Currently, aside from symptomatic treatments for neuropathic pain, there are no treatments to prevent CIPN or treat established CIPN. We discuss recent articles addressing clinimetric issues and treatment of CIPN.
Learn More >