Flaminia Coluzzi

Ultra-processed foods (UPFs) represent one of the major sources of industrial food additives (IFAs). The increasing consumption of UPFs has determined an enhancement of dietary exposure to IFAs, including phosphorus, sodium and potassium-based compounds, and to emulsifiers, preservatives and synthetic colorants. Although these additives improve food stability and extend shelf life, increasing evidence suggests that they may adversely affect kidney health by promoting oxidative stress (OS), systemic chronic inflammation, gut dysbiosis, endothelial dysfunction and disturbances in mineral metabolism, mainly in chronic kidney disease (CKD) patients. This review aims to analyze the current evidence on the impact of IFAs on kidney health in the general population and on the progression of CKD in nephropathic patients. It discusses the potential of natural bioactive compounds (NBCs) as safer alternatives capable of combining food preservation with kidney protection. The literature data show that high UPF consumption is associated with an increased risk of CKD onset and progression. In contrast, NBCs, which substitute the use of IFAs, exhibit antioxidant, anti-inflammatory, antimicrobial and nephroprotective properties. They also show promising technological applications as natural preservatives, emulsifiers and colorants, supporting their use as alternatives to IFAs. In conclusion, IFAs might contribute to CKD onset and progression, whereas NBCs represent promising alternatives capable of combining technological functionality with potential benefits, above all, on renal health. However, well-designed clinical trials are required to confirm the long-term efficacy and safety of NBCs in CKD prevention and management.

Obesity is a complex, heterogeneous, chronic, and progressive disease, which correlates with an augmented risk of developing several comorbidities, including painful conditions, such as osteoarthritis. In this review, authors present for the first time the term meta-neuroinflammation for describing how the chronic, low-grade systemic inflammation, that occurs in obesity, may trigger oxidative stress and neuroinflammatory processes. Both the peripheral and the central nervous system are involved in neuroinflammation, leading to central sensitization and pain chronification, which leads to the observed increased incidence in obese patients of chronic pain syndromes, particularly osteoarthritis, low back pain, fibromyalgia, headache, and diabetic peripheral neuropathy. Possible mechanisms by which obesity may cause meta-neuroinflammation include adiposopathy, gut microbiota dysbiosis, and compromised integrity of blood–brain barrier, which could explain obesity-related depressive and neurodegenerative disorders. Preclinical data suggest the meta-neuroinflammation as a potential target of treatment in obese patients with degenerative joint disease. Based on these observations, targeted therapeutic strategies may include systemic administration of ultramicronized palmitoylethanolamide (um-PEA), well known for its neuroprotective, anti-neuroinflammatory, and analgesic actions, and comicronized PEA–rutin and hydroxytyrosol to restore intestinal eubiosis, with beneficial effects on body weight and mental disorders. Finally, Adelmidrol, as a PEA congener, could be considered for mitigating intra-articular meta-neuroinflammation in knee osteoarthritis.

Given the growing mean age of population, a substantial percentage of patients undergoing surgical procedures can be classified as elderly or as frail, because oncological, malnourished, anemic, depressed or with chronic organ failure. Identification of frailty in the preoperative assessment is essential for implementing the application of ERAS protocols, whose main principles are potentially tailored for frail patients. Preoperative optimization and minimal invasiveness are mandatory to improve baseline resilience of these subjects. In particular, being pain a strong determinant of frailty, adequate multimodal postoperative analgesia is strongly recommended. Despite the limited number of studies available, current evidence suggests that application of ERAS protocols to frail patients may reduce the rates of postoperative complications.

Nociplastic pain has recently been introduced as a third entity for identifying patients suffering from chronic pain that arises from altered nociception, without evidence of peripheral nociceptors activation or alterations of the somatosensory system. Currently, the main challenge of nociplastic pain is that it remains a diagnosis of exclusion, since no specific biomarkers are available. Positron emission tomography (PET) neuroimaging studies, using selective translocator protein (TSPO) radiopharmaceuticals, specific for microglia activation, showed a strong correlation between neuroinflammation and nociplastic pain: in particular, in fibromyalgia (FM), which is the prototype disease. Neuroimaging studies identified key brain changes associated with pain processing and neuroinflammation in patients suffering from widespread pain, often associated with sleep, mood disorders, and cognitive impairment. The present review will provide an overview on the role of neuroinflammation in nociplastic pain, focusing on preclinical evidence of microglia activation and advances in PET neuroimaging. Understanding the role of neuroinflammation could have relevant implications in selecting targeted therapeutic strategies and improving analgesic efficacy.

An Italian multidisciplinary team of pain management experts reviewed ibuprofen and paracetamol in combination for acute pain. Effective treatment of acute pain should target both inflammation and pain signaling to reduce suffering and prevent the development of persistent pain. The combination of a non-steroidal anti-inflammatory drug (NSAID) and paracetamol appears to be a logical choice: paracetamol primarily acts centrally, while NSAIDs inhibit the inflammation that perpetuates the pain response. Both drugs are rapidly absorbed, reaching maximal concentrations within 1-2 hours. Coadministration may enhance paracetamol absorption, leading to earlier onset of pain relief. The rate of drug interactions between ibuprofen and paracetamol is low, and the two do not directly interact with each other. Multiple studies and meta-analyses have shown that the combination is more effective than placebo or either drug used alone in relieving postoperative pain and reducing the need for rescue analgesia after surgery or acute musculoskeletal injury. The most commonly evaluated daily dosage was ibuprofen/paracetamol 400/1,000 mg. A single-pill combination of ibuprofen and paracetamol also reduces the incidence of persistent pain compared with other systemic analgesics, with an adverse-effect profile similar to, or better than, placebo or monotherapy. When prescribing ibuprofen/paracetamol, physicians should consider age, blood pressure, and concomitant medications, particularly aspirin and warfarin.

Osteoarthritis (OA) is one of the most frequent orthopedic disorders and a common cause of chronic pain, which is one of the most important factors in recommending total joint arthroplasty (TJA). Due to a greater need for pain relief and improved mobility in the OA population, TJA procedures are in high demand, and most patients with OA experience long waiting times. Waiting for TJA places a significant burden on patients as a result of worsening pain and functional deterioration. Therefore, optimizing pre-operative circumstances in these patients is essential to target analgesic interventions, preserve post-operative quality of life, and minimize post-operative outcomes such as chronic post-surgical pain. Achieving optimal pain control before surgery remains an unmet need, and it is difficult to devise a one-size-fits-all analgesic regimen. Pain is a challenge for orthopedic healthcare professionals (OHCPs), and orthopedic patients are notably less satisfied than patients undergoing other surgeries in terms of pain management. We reviewed the latest clinical evidence on pain management in patients with OA wait-listed for TJA to help OHCPs effectively manage their pain. Here, we provide actionable suggestions to strengthen orthopedic surgeons’ competency in pain assessment and therapy selection. By integrating the perspectives of an orthopedic surgeon and a pain therapist, we also introduce the concept of “pain prehabilitation” and propose integrating it into standard care protocols during the TJA wait-list period to optimize TJA outcomes and prevent the development of chronic post-surgical pain.

Background/Objective: The long-term implications of spinal interventional pain procedures (IPPs) remain underexplored. This study aimed to evaluate pain intensity, overall health quality, and disability over a four-year period following an IPP, while also assessing physical therapy (PT) compliance, the need for repeated procedures, and analgesic consumption. Methods: A prospective observational study with retrospective registration was conducted on patients with chronic spinal pain at Hamad Medical Corporation (HMC), Qatar. Patients were assessed using the Numeric Rating Scale (NRS), the Oswestry Disability Index (ODI), and the EuroQol 5-Dimension Index (EQ-5D). Additional tools included the EQ-Health Visual Analog Scale and the Patient Global Impression of Change (PGIC). Follow-ups were performed at 6, 12, 24, 36, and 48 months. Results: A total of 766 patients were initially recruited, of whom 174 met the inclusion criteria. All patients demonstrated significant improvement across all outcome measures compared to the baseline. No significant differences were observed in pain or functional outcomes between PT-compliant and non-compliant groups. By the end of this study, 56.9% of patients reported reduced analgesic use, while 43.1% reported increased use. The patient satisfaction data showed that 55% (62/113) of those receiving a single IPP were satisfied, compared to 54% (33/61) in the multiple IPP group. The PGIC satisfaction scores revealed no statistically significant differences (p = 1). Overall health status, as measured by the EQ-5D Health scale, also showed no meaningful differences between groups. Conclusions: Despite several limitations, patients reported sustained improvement and satisfaction four years post-IPP. PT compliance did not appear to significantly influence long-term outcomes. Further research is needed to identify factors affecting post-IPP recovery and medication usage.

Obesity is a complex, heterogeneous, chronic and progressive disease, which correlates with an augmented risk to develop several comorbidities with an enhanced risk of death. In addition to metabolic and cardiovascular diseases, obesity is related to depressive disorders and neurodegenerative diseases, in which gut microbiota dysbiosis plays a central role in triggering the meta-neuroinflammation through the gut-brain axis. In obese patients, the release of inflammatory mediators by dysfunctional adipocytes and the oxidative stress induces meta-neuroinflammation, which have been identified as the main physio-pathological pathway underlying chronic pain syndromes, particularly osteoar-thritis, low back pain, fibromyalgia, headache, and painful diabetic peripheral neu-ropathy. Both the peripheral and the central nervous system are involved in neuroin-flammatory processes, leading to central sensitization and pain chronification. Me-ta-neuroinflammation is also a potential peripheral target of treatment in degenerative joint disease, in order to minimize the traditional pharmacological approaches use. The ultramicronized palmitoylethanolamide is able to control the body weight, to exert neuroprotective, anti-neuroinflammatory and analgesic actions, and to restore intestinal eubiosis, with beneficial effects on mental disorders via the gut-brain axis. Finally, adelmidrol, as a PEA congener, available for intra-articular injection associated with hyaluronic acid, has been shown to modulate meta-neuroinflammation in knee osteo-arthritis.

The burden of cancer is growing in almost every country. Bone metastases significantly affect the prognosis and lead to an increase in mortality and morbidity. The management of cancer-induced bone pain (CIBP) still shows various unmet needs. Opioid use is burdened by a number of possible side effects. Moreover, recent progresses in cancer treatment significantly increased the life expectancy of cancer patients, even those with metastatic disease. In this narrative review, we reported the main findings regarding TRP channel function in cancer pain models. TRP cation channels play a key role in different functions of cancer cells, including the regulation of their potential for metastasization, and are the main channels involved in the pathways of pain perception, through peripheral and central effects. Genetic deletion decreased pain sensitivity following tumour cell inoculation. Preclinical data suggest a potential role for modulators of some TRP channels, such as TRPV1, TRPA1, TRPM7 and TRPM8. Clinical results are still scarce; however, the physiological role in modulating bone remodelling and the involvement of TRP channels in preclinical models of bone cancer pain have garnered interest as areas of research in the last few years, as innovative analgesic strategies that may overcome the long-term side effects of opioids.