Neuropathic pain in an elderly population of an urban area of iran with a special focus on carpal tunnel syndrome : epidemiological aspects, clinical characteristics, and non-surgical therapy

Background: People are getting older, and aging problems and disorders are increasing fast. Knowing the rates, causes, symptomatology, treatment, relief, and prognosis of associated disorders can help and facilitate the elderly, their families, primary health care providers, and health policymakers. Chronic pain in the elderly is a common complaint and its prevalence differs in society and depends on many factors, including type, severity, and localization but also comorbidities, socio-economic factors, and genetics. Pain is in two main categories, nociceptive and neuropathic. Nociceptive pain usually occurs after end-organ damage or derangement such as musculoskeletal problems, osteoarthritis, or trauma. Neuropathic pain arises from central or peripheral nervous system injuries. One of the most common types of peripheral neuropathic pain is hand pain caused by the carpal tunnel syndrome (CTS). Hand pain and CTS are common among the elderly, especially in women. The etiology usually remains uncertain until the late stages of the disorder, when intrinsic hand muscles become weak or atrophy, when it is too late to manage the CTS adequately. Thus, it is important to be aware of its clinical symptoms, signs, and provocation maneuvers, but also to have a noninvasive diagnostic tool when CTS is suspected. Also, it is important to have a solution for mild and moderate types of CTS to prevent surgery in older adults, especially in those with frailer constitutions. Objectives: We evaluated the prevalence of pain, with special focus on neuropathic pain and CTS, in a large population-based study in Tehran, the capital of Iran. We chose CTS as being the most common symptom of focal neuropathy and evaluated the median nerve by noninvasive, high-resolution ultrasonography. We investigated and diagnosed CTS and determined its severity. Following the results of our diagnostic study, we performed interventional treatment studies on patients diagnosed with CTS. To find the optimum steroid dose site, we examined three different doses of steroid in a mixture injected in the tunnel near the affected nerve medianus with an adhesion removal technique called hydro dissection. Finally, we compared different methods of injection in our last study to examine a hypothesis about nonsurgical flexor retinaculum release. Methods and material: More than 5,000 patients were investigated randomly by a multistage cluster sample. Participants were then interviewed using a sociodemographic checklist, a standard pain questionnaire, and general health through GHQ-28. In the 2nd study, demographics were noted along with the clinical presentation of CTS, and the median nerve anatomy was assessed by ultrasound and electrodiagnostic tests. The median nerve cross-sectional area (CSA) at the tunnel inlet and four different areas over the median nerve were measured and analyzed. In the 3rd paper with an intervention, we designed a prospective three group, randomized, double-blind trial to evaluate 40, 80, and 0 mg triamcinolone in a mixture of 3 mL containing 1 cc of lidocaine 2%. Outcome measures included the Boston Carpal Tunnel Questionnaire, VAS (visual analog scale), median nerve conduction criteria, and the ultrasound median CSA. All data were recorded at the baseline, 14 days, 1 month, and 6 months after the injection. In the 4th study, the design was similar to the 3rd one, though we had only two groups and the injecting mixture was 40 mg of triamcinolone and 1 cc of lidocaine 2%. The location of the injection was different with one group injected in the flexor retinaculum and the other near the nerve. All data were recorded as in the 3rd study but only at baseline, and 6 weeks after injection. Results: We found a 13.7% prevalence of chronic neuropathic pain and 30% of chronic nociceptive pain, overall chronic of 31.7% and overall acute of 39.1% which, in combination, add up to 70.8%. The major comorbidities were osteoporosis, diabetes, disability, and stroke. In the 2nd study with 203 CTS and 103 control subjects, CSA at the tunnel inlet with a threshold of 8.5 mm2 had a sensitivity and specificity of 96.9% and 93.6% respectively. In the 3rd study with 161 patients, we did not find any statistically significant differences between groups, i.e., all groups with a steroid dose had similar results. In the last study with 50 eligible subjects randomized into two groups, there was a significant improvement in Boston scores (p-value 0.023), VAS (p-value 0.026), and ultrasonographic measure (p-value 0.004), in favor of intra-flexor retinaculum steroid injection compared to near the nerve. Conclusions: Neuropathic pain prevalence is relatively high; 13.7% among Iranian elderly people, and the overall pain is very high around 70 %. It should be addressed by health policymakers, primary care physicians, and caregivers. High-resolution ultrasonography is a noninvasive diagnostic tool with about 95% sensitivity and specificity in detecting CTS in the elderly and should be introduced as a screening tool by primary physicians engaged in elderly care. The use of plain lidocaine was beneficial in managing CTS in elderly patients, and we did not find any superiority for the steroids. Finally, in case of no contraindication for steroids, we prefer the intra-flexor retinaculum injection. Larger studies should be performed in future studies in this field to confirm our results

Neuropathic Pain Prevalence of Older Adults in an Urban Area of Iran: A Population-Based Study

Background. Pain prevalence would increase as the population grows older, but the exact prevalence rate is not apparent in Iran. Objectives. This study, therefore, set out to reveal the prevalence of pain, especially neuropathic type and explore its associated comorbidities among Iranian older adults in a large urban population-based survey. Methods. 5326 older people, aged � 60 years, were randomly chosen by a multistage, cluster sampling method. The selected people then were interviewed by using the following instruments: a standard questionnaire about pain, questions of interview part of Douleur Neuropathique 4 Questions (DN4) and its comorbidities, GHQ-28, and a sociodemographic checklist. Descriptive statistics and multiple regression analysis were conducted to analyze the gathered data. Results. The average of the participants' age was 68.92 ± 7.02 years. Of 5326 participants, 2529 (47.5) of participants were male. About one-third of this population had chronic pain. Chronic neuropathic pain prevalence was 13.7 and nociceptive in 30. Knee pain (20.6) and feet dysesthesia (7.8) were the most common sites of nociceptive and neuropathic pain, respectively. Results of multiple regression analysis revealed that the major comorbidities of chronic pain were osteoporosis, disability, diabetes mellitus, and stroke. Neuropathic pain experiences were significantly associated with GHQ-28 scores (t=-11.42, P<0.001). Conclusions. In addition to neuropathic pain, other subtypes of pain prevalence and the comorbidities are determined in the community-dwelling elder adults. This study highlights the importance of neuropathic pain and its adverse consequences and can be used to manage this populations' needs in Iran effectively. © 2019 Reza Salman Roghani et al

Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition

Colorectal cancer (CRC) is the third most prevalent form of cancer in the United States and results in over 50,000 deaths per year. Treatments for metastatic CRC are limited, and therefore there is an unmet clinical need for more effective therapies. In our prior work, we coupled high-throughput chemical screens with patient-derived models of cancer to identify new potential therapeutic targets for CRC. However, this pipeline is limited by (1) the use of cell lines that do not appropriately recapitulate the tumor microenvironment, and (2) the use of patient-derived xenografts (PDXs), which are time-consuming and costly for validation of drug efficacy. To overcome these limitations, we have turned to patient-derived organoids. Organoids are increasingly being accepted as a “standard” preclinical model that recapitulates tumor microenvironment cross-talk in a rapid, cost-effective platform. In the present work, we employed a library of natural products, intermediates, and drug-like compounds for which full synthesis has been demonstrated. Using this compound library, we performed a high-throughput screen on multiple low-passage cancer cell lines to identify potential treatments. The top candidate, psymberin, was further validated, with a focus on CRC cell lines and organoids. Mechanistic and genomics analyses pinpointed protein translation inhibition as a mechanism of action of psymberin. These findings suggest the potential of psymberin as a novel therapy for the treatment of CRC

Normal Values and Reproducibilitiy of Electric Current Perception Threshold in Sensory Fibers

Objective: Routine electrodiagnosis (EMG-NCS) has some shortcomings in the evaluation of peripheral nervous system, auch as autonomous nervous system evaluation, in pure sensory radiculopathies and acute hyperesthetic stages of neuropathies. Quantitative sensory testings such as current perception threshold (CPT) with electrical stimulations are suggested for above mentioned pathologies. Ttest results should be compared with a normal value of similar identical population. This study is conducted to determine normal value and reproducibility of CPT in the Iranian population. Materials & Methods: Fifty normal volunteers (32 men, 18 woman) in the range of 20-40 years without exclusion criteria (such as neuro- musculoskeletal disorders, diabetes mellitus and alcoholism) were recruited with simple randomized selection and CPT test was conducted on C8 (4th finger) and L5 (1st Toe)dermatomes. To determine test’s reproducibility, 6 persons (4 men, 2 women) were examined 3 times a day, 2 day per week. Collected data were analyzed to determine mean and standard deviation. Results: Normal values of CPT test was defined as one standard deviation from mean of our CPT data. These values are in C8 dermatome 2000 Hz: 2.04± 47 250 Hz: 0.75±0.25 5 Hz: 0.76±0.3 and for L5 dermatome 2000Hz: 2.83± 0.73 250 Hz: 1.24 ± 45 5Hz: 0.76± 0.3 To determine our results reproducibility and reliability, Alpha- cronbach (existed in SPSS software) was used and %98.5 & 99% were obtained for C8 & L5 dermatomes respectively. Conclusion: Our findings are about C8 & L5 dermatomes which could be used as a normal Values for such dermatomes. Regarding to its good correlation with international results we can use international references as a normal Valueswith consideration of each clinic’s reproducibility should be assessed individually