Accepted

Regenerative pain medicine, which seeks to harness the body's own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuroimmune modulation. In this Review, we discuss recent progress in mechanistic understanding of nociceptive sensitization in chronic pain with a focus on neuroimmune modulation. We also examine the spectrum of regenerative outcomes, including preclinical and clinical outcomes. We further distinguish the analgesic mechanisms of regenerative therapies from those of cellular replacement, creating a conceptual and mechanistic framework to evaluate future research on regenerative medicine.

Recent efforts to update the definitions and taxonomic structure of concepts related to pain have revealed opportunities to better quantify topics of existing pain research subject areas.

Chronic low back pain (CLBP) affects nearly 20-25% of the population older than 65 years, and it is currently the main cause of disability both in the developed and developing countries. It is crucial to reach an optimal management of this condition in older patients to improve their quality of life. This review evaluates the effectiveness of physical activity (PA) to improve disability and pain in older people with non-specific CLBP. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to improve the reporting of the review. Individual risk of bias of single studies was assessed using Rob 2 tool and ROBINS-I tool. The quality of evidence assessment was performed using GRADE analysis only in articles that presents full data. The articles were searched in different web portals (Medline, Scopus, CINAHL, EMBASE, and CENTRAL). All the articles reported respect the following inclusion criteria: patients > 65 years old who underwent physical activities for the treatment of CLBP. A total of 12 studies were included: 7 randomized controlled trials (RCT), 3 non-randomized controlled trials (NRCT), 1 pre and post intervention study (PPIS), and 1 case series (CS). The studies showed high heterogeneity in terms of study design, interventions, and outcome variables. In general, post-treatment data showed a trend in the improvement for disability and pain. However, considering the low quality of evidence of the studies, the high risk of bias, the languages limitations, the lack of significant results of some studies, and the lack of literature on this argument, further studies are necessary to improve the evidences on the topic.

Our ability to sense mechanical cues from our environment depend on the capacity of molecular sensor capable of converting mechanical energy into biochemical or electrical signals. This process, termed mechanotransduction, relies on the activity of mechanosensitive ion channels (MSCs) that are expressed in most tissues, including cells of the inner and outer ear, sensory and sympathetic neurons, and vascular cells. However, the precise role these channels play in the physiology of the cells and organs, where they are expressed is not completely understood. In this review, we will explore some of the recent findings on the role of MSCs to our sense of mechanical pain.

Interstitial cystitis/bladder pain syndrome is a debilitating condition of unknown etiology characterized by persistent pelvic pain with lower urinary tract symptoms and comprises a wide variety of potentially clinically useful phenotypes with different possible etiologies. Current clinicopathological and genomic evidence suggests that interstitial cystitis/bladder pain syndrome should be categorized by the presence or absence of Hunner lesions, rather than by clinical phenotyping based on symptomatology. The Hunner lesion subtype is a distinct inflammatory disease with proven bladder etiology characterized by epithelial denudation and enhanced immune responses frequently accompanied by clonal expansion of infiltrating B cells, with potential engagement of infection. Meanwhile, the non-Hunner lesion subtype is a non-inflammatory disorder with little evidence of bladder etiology. It is potentially associated with urothelial malfunction and neurophysiological dysfunction, and frequently presents with somatic and/or psychological symptoms, that commonly result in central nervous sensitization. Animal models of autoimmune cystitis and neurogenic sensitization might serve as disease models for the Hunner lesion and non-Hunner lesion subtypes, respectively. Here, we revisit the taxonomy of interstitial cystitis/bladder pain syndrome according to current research, and discuss its potential pathophysiology and representative animal models. Categorization of interstitial cystitis/bladder pain syndrome based on cystoscopy is mandatory to design optimized treatment and research strategies for each subtype. A tailored approach that specifically targets the characteristic inflammation and epithelial denudation for the Hunner lesion subtype, or the urothelial malfunction, sensitized/altered nervous system and psychosocial problems for the non-Hunner lesion subtype, is essential for better clinical management and research progress in this complex condition.