Why are we still missing the pain? - Rethinking diabetic neuropathy in primary care - lessons from the REGENERAR study

Sep 28, 2026

Letter to the editor discussing the clinical importance of painful diabetic peripheral neuropathy and the need for improved detection in primary care. It highlights high baseline pain prevalence (77.5%) and neuropathic pain classification (48.3%), notes gaps between patient-reported pain and clinical diagnosis, and considers external validity of the multicenter design. It addresses limitations in professional participation and unassessed cognitive status, argues for systematic phenotypic characterization, and emphasizes tailored treatments, education, psychological management, and physical exercise.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages3

Reading Time8 min

AccessFree to download

Letter to the editor

Key findings and comparison with prior studies

Study strengths and observed improvements

Limitations and unanswered factors

Need for systematic phenotypic characterization

Evidence for phenotype-specific management

Education, psychosocial impact, and physical exercise

Letter to the editor Why are we still missing the pain? Rethinking diabetic neuropathy in primary care – lessons from the REGENERAR study Antonio Alcántara Montero centro de Salud trujillo, trujillo, cáceres, Spain this letter to the editor is written in response to the article by Antunes et al., recently published in Future Science oA, on the prevalence of pain and health literacy in patients with diabetic peripheral neuropathy (dPN) in Portugal (reGeNerA r Study) . the study represents a valuable contribution to the clinical and epidemiological understanding of a complication that is both common and underdiagnosed [1] . From Spain, where type 2 diabetes affects more than 14% of the adult population, i observe the findings with particular interest, considering them extrapolable to other european contexts and relevant for improving primary care [2] . one of the most striking findings of the reGeNerA r study is the high prevalence of pain among patients with dPN: 77.5% at baseline, with 48.3% classified as neuropathic pain according to the dN4 questionnaire [3] . these values are considerably higher than those reported in previous european studies, where prevalence ranged from 5.8% to 40.3%[4] . in Spain, a multicenter study found that up to 80% of patients with diabetes experience pain, although only half receive a diagnosis of painful dPN [5] . this gap between patient perception and clinical diagnosis highlights the urgent need to strengthen detection tools in primary care through standardized protocols and targeted training. the multicenter design carried out in primary care settings provides strong external validity to thereGeNerA r study. Moreover, an improvement was observed in patients’ literacy regarding pain as a symptom of diabetes [6], together with positive lifestyle changes: reduced alcohol and tobacco consumption and a modest increase in physical activity. these findings suggest that participation in clinical studies may have benefits that extend beyond data collection [7] . Nevertheless, important limitations are evident. the limited participation of healthcare professionals in the literacy questionnaires does not allow robust conclusions about their knowledge and practices. Patients’quality of life, assessed with the eQ-5d-5L, remained consistently suboptimal, with a median score of 70/100, showing that pain continues to have a major impact on well-being. in addition, cognitive status was not evaluated, a factor that could influence the interpretation of literacy results, particularly in older populations. recent studies have demonstrated that cognitive function may differ between patients with painful and painless dPN, potentially acting as a confounding factor [8] . in this context, i believe it is time to move toward a systematic phenotypic characterization of dPN. identifying clinical phenotypes—painful, painless, or mixed—provides deeper insight into the underlying pathophysiological mechanisms and facilitates the selection of more appropriate treatments [9] . this approach is consistent with the principles of personalized medicine and could be particularly valuable in primary care, where symptom variability and multimorbidity often complicate diagnosis and management of neuropathic pain. the literature strongly supports this approach. Studies have shown that patients with the painful phenotype demonstrate greater small fiber involvement and central sensitization [10], which justifies the use of specific treatments such as gabapentinoids or dual serotonin–norepinephrine reuptake inhibitors [11] . in contrast, patients with the painless phenotype present more pronounced distal sensory loss, making them more vulnerable to injuries and amputations and therefore requiring more intensive preventive measures [12] . in Spain, health literacy continues to be a major challenge. A study conducted in ourense reported that 81.5% of patients with type 2 diabetes had insufficient literacy levels,

FAQs

What does the letter identify as the most striking finding of the REGENERAR study?

The letter emphasizes the high prevalence of pain among patients with diabetic peripheral neuropathy: 77.5% at baseline and 48.3% classified as neuropathic pain.

Why does the letter argue that stronger detection is needed in primary care?

It points to a gap between patients’ perception of pain and clinical diagnosis, and calls for standardized detection tools and targeted training for healthcare professionals.

What approach does the author recommend for improving understanding and treatment?

The author recommends systematic phenotypic characterization of diabetic peripheral neuropathy (painful, painless, or mixed) to clarify mechanisms and support more appropriate, phenotype-informed treatments.

Sep 28, 2026

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