Maurizio Evangelista

The journal retracts the article, “Formyl Peptide Receptor 1 Signaling in Acute Inflammation and Neural Differentiation Induced by Traumatic Brain Injury”

Chronic pain represents a major challenge for healthcare systems worldwide. Pharmacological agents such as opioids, gabapentinoids, and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used depending on the pain type (nociceptive, neuropathic, or nociplastic), but their use is often limited by adverse effects. Nutraceuticals and dietary supplements have emerged as potential adjuvants to conventional pain management, offering improved safety profiles. This narrative review aims to evaluate the preliminary evidence on the efficacy and safety of selected plant-derived nutraceuticals for pain management. Particular attention is given to a new fixed nutraceutical formulation containing lycopene, sulforaphane (Brassica oleracea), silymarin (extracted from Silybum marianum), reduced glutathione, escin (Aesculus hippocastanum), tryptophan, and green tea (Camellia sinensis). Although this formulation has not yet been evaluated in clinical trials, preliminary data suggest that individual components may target different pain mechanisms. None of the currently available nutraceuticals act comprehensively on all pain types. Additionally, the inclusion of hepatoprotective compounds (e.g., glutathione and silymarin) may be advantageous for patients receiving multiple medications. Current evidence on these nutraceuticals remains limited and primarily preclinical. Further randomized controlled trials are needed to confirm their efficacy and safety in human pain management.

Osteoporosis is a chronic disease affecting individual, public and social health. Few data are available about the awareness of osteoporosis in Italy. The main purpose of our study is to evaluate the perception of osteoporosis in a selected sample of subjects of different age and sex. This is a survey involving 299 adults (aged 18-75 years) designed to assess knowledge about osteoporosis and fracture risk conducted by a multidisciplinary research team of LUISS Guido Carli University. The knowledge of osteoporosis resulted almost high among the participants (97%) and most of them considered it a disease (86.1%). Most respondents (30.5%) did not know if they might be at risk of osteoporosis, especially the youngest (43.5%). A high percentage of participants (73.8%) considered a family history of osteoporosis the principal risk factor for bone loss, while only 8.9% thought that moderate to vigorous physical activity could favor bone loss. Many women (17.4%) did not consider menstrual irregularities a risk factor for osteoporosis. As for nutrients, 79.5% and 89.4% of subjects, respectively, thought that vitamin D and calcium might be useful to prevent bone loss. The majority of sample (74.8%) did not know the public and social impact of osteoporosis. Although this survey involved a selected population and, thus, it cannot reflect the Italian general knowledge of osteoporosis, it might contribute to estimate the actual awareness of osteoporosis among people, regardless of their current bone health status, highlighting areas for further educational and research efforts.

Chronic pain represents a complex debilitating condition that extends beyond the protective function of physiological pain, often persisting as an independent disease entity. Chronic primary and secondary pain syndromes reflect a multifaceted continuum involving nociceptive, neuropathic and nociplastic mechanisms. The maladaptive plasticity of the peripheral and central nervous system (encompassing the ascending and descending pain pathways) sustains hypersensitivity and correlates with comorbid alterations in mood, cognition, sleep, and fatigue, underpinned by functional reorganization of brain networks. In this scenario traditional analgesics frequently demonstrate limited efficacy, while current guidelines recommend antiepileptic agents and antidepressants, particularly gabapentinoids and duloxetine, a first line pharmacological options. This review explores the mechanistic rationale and clinical evidence supporting the combined use of gabapentinoids and duloxetine in chronic pain management. These agents act on distinct yet complementary targets: gabapentinoids reduce excitatory neurotransmission via modulation of calcium channel activity, while duloxetine restores descending noradrenergic inhibition and alleviates comorbid symptoms. Clinical trial and meta-analyses highlight their individual efficacy in diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia. Among gabapentinoids, pregabalin exhibits a favorable pharmacokinetic profile that allows rapid titration and demonstrates effectiveness against anxiety-related sleep disorders. Importantly, emerging evidence suggests that their combination may yield superior pain relief and functional improvement compared with monotherapy, particularly in patients with residual pain. This review provides a proof of concept by bridging theoretical knowledge and real-life clinical settings aiming to develop treatment protocols based on predominant pain mechanisms that can effectively control hypersensitivity and improve quality of life.

Both neuropathic and nociplastic pain (non-nociceptive pain) are characterized by a similar pattern of clinical symptoms, including numbness, dysesthesia, tingling, and pricking. Whereas nociplastic pain results from altered nociception without indication of tissue damage or a somatosensory system lesion, neuropathic pain is caused by a disease or lesion affecting the somatosensory system. The available therapeutic options consist of antiepileptic drugs, antidepressants, and muscle relaxants. Unfortunately, symptoms are often refractory, and increasing drug dosage may lead to adverse events. In this narrative review, we searched PubMed, MEDLINE, Cochrane, and EMBASE databases from their inception up to 26 July 2025, using the key words “duloxetine,” “pregabalin,” and then ‘‘combination,’’ “nociplastic pain,” “neuropathic pain,” “efficacy,” “safety,” “pharmacology,” “pharmacokinetic,” and “pharmacodynamic.” We evaluated the role of combination therapy with duloxetine, a serotonin–norepinephrine reuptake inhibitor, and pregabalin, an antiseizure medication that acts on voltage-gated calcium channels α2δ subunit, in patients with neuropathic or nociplastic pain. The literature data indicate that combination therapy has synergistic effects, leading to fewer adverse events in specific categories of patients. Available evidence showed that combination therapy is generally not inferior to monotherapy, with slight differences in safety outcomes depending on supplementation, drug labels, and titration. These results indicate that even if not superior, combination therapy may be an alternative to monotherapy in selected patients: those who experience side effects from higher dosages of duloxetine or pregabalin and for whom symptom relief from dose reduction alone is not possible; those who use medications that interact with duloxetine; those who suffer from anxiety–depression, where pain is closely linked to mental symptoms; and those who have central neuropathic pain (often refractory).

Chronic pain is a serious concern for the healthcare system, considering the high public expense. Many drugs, such as opioids, non-steroidal anti-inflammatory drugs, amitriptyline, duloxetine, and pregabalin, can be used considering the type of pain (nociceptive, neuropathic, or nociplastic). This is because prescription drugs have a significant negative impact on patient health and the economy, increasing the risk of drug interactions and side effects. Nutraceuticals/supplements may be useful to reduce safety issues, particularly in elderly patients. A new fixed nutraceutical formulation containing lycopene (Solanum lycopersicum), sulforaphane (Brassica oleracea), silymarin (Silybum marianum), reduced glutathione, escin (Aesculus hippocastanum), tryptophan, and green tea (Camellia sinensis) can be used to manage the pain even if its action on pain has not been proved in clinical trials. Nevertheless, the evidence of a strong anti-nociceptive effect by escin and green tea, alongside the antioxidant and anti-neuropathic pain properties of other components, may be useful as adjuvant therapy to reduce drug dosage and prescription. Additionally, patients in polytherapy may benefit from the presence of two hepatoprotective compounds, such as glutathione and silymarin. The aim of this narrative review is to evaluate the data available on both efficacy and safety of the described nutrients in the management of pain.

Introduction: Neuropathic pain is defined as pain induced by a lesion or disease of the somatosensory nervous system. Pharmacological and non-pharmacological treatments are frequently employed. In the current clinical investigation, we assessed the effects of sex on the safety and effectiveness of medications used to treat neuropathic pain. Methods: We conducted a prospective analysis between 1 February 2021 and 20 April 2024, involving patients with neuropathic pain referred to the Ambulatory of Pain Medicine of “Renato Dulbecco” University Hospital in Catanzaro (Calabria, Italy). Patients over 18 years old with signs of neuropathic pain (Douleur Neuropathique en 4 questionnaire ≥ 4) were included. Exclusion criteria comprised patients with Alzheimer’s disease; patients with nociplastic or nociceptive pain; and patients with neoplasms. Patients with fewer than two accesses to ambulatory care were excluded, as were those who did not sign the informed consent. Clinical data were collected from each enrolled patient and subsequently analyzed, considering clinical outcomes. Sex and gender differences in efficacy were estimated using multivariate linear modeling and propensity-score matching. Results: During the study, 531 patients were screened, and 174 were enrolled (33.5%, mean age 61.5 ± 13.1; 64 males and 110 females, mean age 60.6 ± 13.4 and 61.96 ± 13.0) in accordance with the inclusion and exclusion criteria. Only minor differences in treatment prescription were observed based on age, body mass index, and comorbidities. Smoking, sex, educational level, and body mass index did not induce a significant change in pain perception. Males required slightly higher, though not significantly, doses of drugs for pain control than females. The treatment was not significantly more effective for females than for males. Females did not exhibit a significantly lower number of adverse drug reactions compared to males. Conclusions: The current study found that there are no appreciable differences between the sexes when it comes to the treatment of neuropathic pain.

Long COVID is a recognized post-viral syndrome characterized by neurological, somatic and neuropsychiatric symptoms that might last for long time after SARS-CoV-2 infection. An ever-growing number of patients come to the observation of General Practitioners complaining of mild or moderate symptoms after the resolution of the acute infection. Nine General Practitioners from the Rome area (Italy) performed a retrospective analysis in order to evaluate the role of the supplementation with Palmitoylethanolamide co-ultramicronized with Luteolin (PEALUT) on neurologic and clinical symptoms reported by their patients after COVID-19 resolution. Supplementation with PEALUT helped to improve all patient-reported symptoms, especially pain, anxiety and depression, fatigue, brain fog, anosmia and dysgeusia, leading to an overall improvement in patients’ health status. To our knowledge these are the first data presented on Long COVID patients collected in a territorial setting. Despite their preliminary nature, these results highlight the pathogenetic role of “non-resolving” neuroinflammation in Long COVID development and consequently the importance of its control in the resolution of the pathology and put the focus on the General Practitioner as the primary figure for early detection and management of Long COVID syndrome in a real-life setting. Future randomized, controlled, perspective clinical trials are needed to confirm this preliminary observation.

In agreement with the International Association for the Study of Pain, chronic pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. To date, there are several types of pain: nociceptive, neuropathic, and nociplastic. In the present narrative review, we evaluated the characteristics of the drugs used for each type of pain, according to guidelines, and their effects in people with comorbidity to reduce the development of severe adverse events.

Chronic pain affects almost 20% of the European adult population and it significantly reduces patients’ quality of life. Chronic pain is considered a multidimensional experience determined by the interaction of several genetic and environmental factors. The effect of specific genetic contributions is often unclear, and the interpretation of the results from studies focused on genetic influences on pain has been complicated by the existence of multiple pain phenotypes. A step forward from genetics could be given by the application of metabolomics and microbiomics tools. Metabolomics is a powerful approach for hypothesis generation in biology, and it aims to analyze low molecular weight compounds, either metabolic intermediates or metabolic end-products, resulting from human or microbial metabolism. Microbiomics is a fast-growing field in which all the microbes are examined together, and as a result, its perturbation may indicate the development of chronic diseases. By applying these methodologies for the study of chronic pain, several differences have been identified. The alteration of the choline-PAF pathway is an intriguing finding recognized by several groups. In our opinion, metabolomics and microbiomics techniques will allow significant progress into the medical field. Patients may benefit from the possibility of being stratified and classified based on their metabolic and microbial profile, which, in the next future, may lead to personalized therapy.