Yukinori Nagakura

OBJECTIVES: Chronic pain is defined as pain that persists or recurs for more than 3 months. This study focuses on neuropathic pain (NP) and fibromyalgia (FM) which are chronic pain states, and aims to identify lifestyle habits associated with their prevalence. Other neurological disorders are also analyzed as references. METHODS: Association between the variable referring to disease prevalence (number of claims for reimbursement of marker drugs) and the variable for lifestyle habits/health examination results (collected from insured individuals aged 40-74 years) was determined by analyzing Japanese nationwide datasets, which were collected in 2018 and aggregated by prefecture. Pregabalin, donepezil, and levodopa were used as marker drugs for the chronic pain states, dementia-related diseases (Alzheimer's disease and Lewy body dementia) and Parkinson's disease (PD), respectively. Pearson's correlation analysis and multiple linear regression analysis were conducted. RESULTS: Variables showing correlation coefficient (|r|)>0.5 were put into the multiple linear regression. Exercise habits (ꞵ=-0.3182), smoking habits (0.3218), daily drinking (0.2683), and alanine aminotransferase>51 U/L (0.2309) were finally incorporated in the equation for pregabalin (R 2=0.7268). Walking speed (-0.4543) and daily drinking (0.5077) were incorporated in the equation for donepezil (R 2=0.5718). CONCLUSIONS: The prevalence of chronic pain states is associated with lifestyle habits, just like the dementia-related diseases. Exercise in daily life is negatively associated with the prevalence of the chronic pain states, although excessive alcohol drinking, smoking, and high serum ALT are positively associated with it. The prevalence of PD seems less associated with lifestyle habits.

INTRODUCTION: Fibromyalgia (FM) is a chronic pain condition characterized by widespread pain and complex comorbidities with a high unmet medical need. Given few past successes in the launch of analgesics with new mechanisms, the implementation of practical biomarkers for drug discovery and development would be necessary to rationally create innovative drugs for chronic pain conditions, including FM. AREAS COVERED: This review surveys the evidence on pathophysiology of FM and the findings regarding the pathophysiology-associated practical biomarker candidates in body fluids (e.g. blood) from the studies in FM patients. This review also summarizes the most commonly used animal models simulating key aspects of clinical FM features. Finally, a strategy for rationally creating innovative drugs for FM is discussed. EXPERT OPINION: Drug discovery and development for FM targeting immune dysregulation/inflammation would be a viable strategy based on the availability of the pathophysiology-associated practical biomarkers (e.g. serum interleukins), which monitor the efficacy of interventions and/or identify responders based on the matching pathophysiology throughout the process from animal models to patients. This strategy could lead to a breakthrough in the development of drugs for FM, a chronic pain condition.

OBJECTIVES: Benign prostatic hyperplasia (BPH) refers to nonmalignant hyperplasia of prostate tissue, which causes lower urinary tract symptoms and has become a global public health concern in the aging population. The purpose of this study is to identify modifiable factors, which would prevent or delay BPH development. METHODS: The association between BPH marker drugs and climate-, socioeconomic-, health condition-, and lifestyle habits-related variables was investigated by analyzing nationwide datasets which were collected in 2018, aggregated by prefecture (administrative unit), and published by Japanese ministries. Uroselective α1 receptor blockers and dutasteride were used as marker drugs referring to BPH prevalence. Correlation analysis, multiple linear regression analysis, and binomial logistic regression analysis were conducted with 47 Japanese prefectures as the unit. RESULTS: The variables which showed |r| > 0.5 by correlation analysis were exercise habits (r = -0.5696), smoking habits (r = 0.6116), and daily drinking (r = 0.6001) for uroselective α1 receptor blockers, and antihypertensive medication (r = 0.5971), smoking habits (r = 0.6598), a small amount of drinking (r = -0.5292), and serum alanine aminotransferase (r = 0.6814) for dutasteride. Multiple linear regression equations were constructed by including these variables (R 2  = 0.5453 for uroselective α1 receptor blockers and R 2  = 0.5673 for dutasteride). Binomial logistic regression analysis found a significant association between climate in the resident area and BPH development. CONCLUSION: This ecological study, analyzing Japanese nationwide datasets, demonstrates that healthy lifestyle habits, especially avoidance of smoking, implementation of exercise in daily life, and a small amount of alcohol consumption, are important to prevent or delay BPH development. High blood pressure and high serum alanine aminotransferase are suggested as risk factors of BPH development.