Cristina Vocca

Background/Objectives: Fibromyalgia (FM) is diagnosed using symptom-based criteria, and clinician-assigned labels may diverge from standardized classification frameworks. FM may also coexist with musculoskeletal and other pain-related conditions. We determined the proportion of patients in a combined referral-based cohort who fulfilled the 2019 ACTTION-American Pain Society Pain Taxonomy (AAPT) criteria after retrospective record-based adjudication and described documented concomitant musculoskeletal or pain-related diagnoses and symptom burden according to AAPT status. Methods: This retrospective, single-center cross-sectional pilot study included consecutive adult outpatients evaluated in a tertiary pain unit between January and April 2026 after referral for suspected FM or with a previous clinician-assigned FM diagnosis. AAPT classification was reconstructed from available longitudinal clinical documentation; the historical look-back varied by record availability and extended approximately 8–10 years in some patients. Results: Among 76 patients (96.1% female), 28 fulfilled the AAPT criteria (36.8%; 95% CI, 26.9–48.1). At least one documented concomitant musculoskeletal or pain-related diagnosis was recorded in 25/28 AAPT MET patients (89.3%; 95% CI, 72.8–96.3) and 26/48 AAPT NOT MET patients (54.2%), corresponding to a crude, unadjusted OR of 7.05 (95% CI, 1.87–26.54; p = 0.002). This association may partly reflect criterion-related overlap and differential diagnostic ascertainment. Exploratory analyses suggested greater symptom and affective burden in the AAPT MET group, whereas NRS pain intensity did not differ. Conclusions: Approximately one-third of this combined referral-based cohort fulfilled the AAPT criteria on retrospective adjudication. Documented concomitant musculoskeletal or pain-related diagnoses were common, but the observed association with AAPT status should not be interpreted as independent or causal. Standardized classification and multidimensional clinical pain phenotyping provide complementary information in chronic widespread pain.

Background/Objectives: Fibromyalgia (FM) is diagnosed using symptom-based criteria, and clinician-assigned labels may diverge from standardized classification frameworks. FM may also coexist with other pain-generating musculoskeletal disorders. We determined the proportion of patients referred for suspected or previously diagnosed FM who fulfilled the 2019 ACTTION-American Pain Society Pain Taxonomy (AAPT) criteria after specialist record-based adjudication and compared documented concomitant pain-related diagnoses and symptom severity according to AAPT status. Methods: This retrospective, single-center cross-sectional pilot study included consecutive adult outpatients evaluated in a tertiary pain unit for suspected or previously diagnosed FM. Routinely collected clinical records were reviewed to determine fulfilment of the AAPT 2019 criteria, identify documented concomitant pain-related diagnoses, and assess symptom severity using FIQR, Zung SAS/SDS, DN4, and NRS measures. Results: Among 76 patients (96.1% female), 28 fulfilled the AAPT criteria (36.8%; 95% CI, 26.9–48.1). Of these, 25 (89.3%; 95% CI, 72.8–96.3) had at least one documented concomitant pain-related diagnosis, compared with 26/48 (54.2%) patients who did not fulfil the criteria (OR, 7.05; 95% CI, 1.87–26.54; p = 0.002). Exploratory analyses showed higher FIQR, SAS, SDS, and DN4 scores in the AAPT MET group, whereas NRS pain intensity did not differ significantly. Conclusions: Approximately one-third of patients in this referral-based cohort fulfilled the AAPT criteria, and concomitant pain-related diagnoses were common. Because the retrospective adjudication, small single-center sample, and potential definitional and detection biases limit causal interpretation, these findings should be considered hypothesis-generating. They suggest that criteria-based classification and clinical assessment provide complementary information when evaluating chronic widespread pain.

Background and objectives: Fibromyalgia (FM) is diagnosed using symptom-based criteria, and clinician-assigned labels frequently diverge from them. FM also coexists with pain-generating musculoskeletal disorders. We determined how many patients referred or labeled as having FM fulfilled the 2019 ACTTION-American Pain Society Pain Taxonomy (AAPT) criteria after specialist assessment and compared concomitant pain-related diagnoses and symptom severity by AAPT status. Methods: Single-center cross-sectional pilot study of consecutive adult outpatients attending a pain unit for suspected or previously diagnosed FM. Clinical records were reviewed to determine fulfilment of the AAPT 2019 criteria, identify documented concomitant pain-related diagnoses, and assess symptom severity (FIQR, Zung SAS/SDS, DN4, NRS). Results: Among 76 patients (96.1% female), 28 fulfilled the AAPT criteria (36.8%; 95% CI, 26.9–48.1%). Of these, 25 (89.3%; 95% CI, 72.8–96.3%) had at least one documented concomitant pain-related diagnosis, versus 54.2% of those not fulfilling the criteria (OR, 7.05; 95% CI, 1.87–26.54; p = 0.002). AAPT MET patients had higher FIQR, SAS, SDS and DN4 scores, whereas NRS did not differ significantly. Conclusion: Approximately one-third of patients with an FM label fulfilled the AAPT criteria, and most of those who did also had a concomitant pain-related diagnosis. Comprehensive assessment for coexisting pain generators remains necessary.

Background: Osteoarthritis (OA) is a heterogeneous joint disorder traditionally considered mechanically driven; however, evidence indicates that inflammatory mechanisms contribute to symptom expression. Exploratory analyses of peripheral biomarkers may provide insights into systemic inflammation in symptomatic knee OA, but formal phenotypic validation requires dedicated clustering or longitudinal studies. Objective: To examine associations between clinical pain, functional impairment, and circulating inflammatory biomarkers in patients with knee OA compared with healthy controls. Methods: In this prospective, single-center study, patients aged 40–80 years with radiographically confirmed knee OA and chronic knee pain were compared with age- and sex-matched healthy controls. Pain intensity and functional status were assessed using the Visual Analogue Scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Circulating inflammatory biomarkers, including cytokines and matrix metalloproteinases, were quantified using multiplex immunoassays. Statistical analyses included adjusted linear regression models, with age and BMI as covariates, and multiple testing correction using the Benjamini–Hochberg procedure (FDR alpha error 5%). Results: OA patients exhibited higher circulating levels of TNF-α, IL-6, IL-8, MMP-1, MMP-3, TNFSF13, TNFSF13B, and pentraxin-3 compared with controls (p < 0.01). No significant sex differences were observed. KOOSs correlated with IL-6 and IL-10 levels, suggesting an association between systemic inflammatory activity and functional limitation. All findings are presented as exploratory and associative. Conclusions: Patients with knee OA display systemic inflammatory biomarker differences associated with pain and functional impairment. These results support the role of inflammation in OA symptoms within an exploratory framework. Larger, longitudinal studies are warranted to validate these observations.

Background: Nutraceuticals are increasingly used in clinical practice for their anti-inflammatory, antiproliferative, and antioxidant properties. This study aimed to evaluate the safety and efficacy of a fixed nutraceutical combination containing chondroitin sulfate, α-lipoic acid, astaxanthin, lycopene, escin, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in improving pain and quality of life in patients with chronic knee osteoarthritis (OA). Methods: This observational study included patients with chronic knee OA who were referred to the ambulatory pain clinic at Dulbecco University Hospital, Catanzaro, Italy. Participants received one tablet daily for three months. Quality of life was assessed using the 36-Item Short Form Health Survey (SF-36), and adverse drug reactions (ADRs) were evaluated using the Naranjo scale. Results: Fifty patients (20 men and 30 women; mean age, 63.6 ± 11.4 years; range, 26–88 years; mean body mass index, 26.9 ± 3.7 kg/m²) were enrolled. Pain symptoms demonstrated a statistically significant improvement over time (p < 0.01). No ADRs were reported during the study period. Conclusions: The fixed nutraceutical combination improved pain and quality of life in patients with chronic knee OA and demonstrated an excellent safety profile.

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.

Background: Nutraceuticals are increasingly used in clinical practice for their anti-inflammatory, antiproliferative, and antioxidant properties. This study aimed to evaluate the safety and efficacy of a fixed nutraceutical combination containing chondroitin sulfate, α-lipoic acid, astaxanthin, lycopene, escin, and omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in improving pain and quality of life in patients with knee osteoarthritis (OA). Methods: This observational study included patients with knee OA referred to the ambulatory pain clinic at Dulbecco University Hospital, Catanzaro, Italy. Participants received one tablet daily for three months. Quality of life was assessed using the 36-Item Short Form Health Survey (SF-36), and adverse drug reactions (ADRs) were evaluated using the Naranjo scale. Results: Fifty patients (20 men and 30 women; mean age, 63.6 ± 11.4 years; range, 26–88 years; mean body mass index, 26.9 ± 3.7 kg/m²) were enrolled. A statistically significant improvement in pain symptoms was observed over time (p < 0.01). No ADRs were reported during the study period. Conclusions: The fixed nutraceutical combination improved pain and quality of life in patients with knee osteoarthritis and demonstrated an excellent safety profile.

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.

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