This bibliometric analysis provides a comprehensive overview of the research landscape surrounding neuropathic pain, focusing on publication trends, collaborative networks, and emerging research themes. Our analysis identified a dynamic yet irregular trajectory in publication activity from 2005 to 2024. While periods of substantial growth were evident, such as the notable peak in publications between 2021 and 2022, these were followed by periods of decline, reflecting an inconsistent upward trend. This fluctuation likely mirrors the evolving priorities within neuropathic pain research, influenced by shifts in funding, advancements in related disciplines, and changes in clinical and scientific focus. This finding is not entirely novel, as a decline in the number of published papers after 2021 was also reported in a bibliometric analysis focusing on neuropathic pain in neurodegenerative diseases [26]. Additionally, the COVID-19 outbreak may have impacted the allocation of clinical resources and shifted the focus of published research topics [27]. However, the significant upward trend observed suggests that fundamental questions in neuropathic pain still need to be addressed. Despite advancements in scientific knowledge and the development of clinical applications, neuropathic pain remains a complex condition that is challenging to manage effectively. This persistent complexity highlights the necessity for ongoing and intensified research efforts, supported by substantial material and human resources, to enhance understanding and improve treatment outcomes. This need was further underscored by forecasting predictions, which indicate a consistently high and stable volume of publications over the next five years, reflecting sustained and growing interest in this field.

The distribution of studies across journals demonstrated considerable dispersion. While most documents were published in prestigious Q1 journals, underscoring their high-quality contributions to the field, a notable proportion appeared in Q3 journals, particularly within the domains of neurology and neuroscience. This pattern suggests that a significant portion of neuropathic pain research is conducted within these disciplines. However, it also highlights a potential gap in the allocation of space for neuropathic pain studies in highly impactful neurology-focused journals, indicating the need for greater recognition of the topic's importance in these outlets. Pain was the journal with the highest impact factor and the largest number of published papers on neuropathic pain. This finding underscores the journal's pivotal role in advancing neuropathic pain research, both in elucidating underlying mechanisms and in developing effective management strategies. Our findings also highlighted the importance of international collaboration in advancing neuropathic pain research. The co-authorship network revealed dense clusters of collaboration, particularly among countries such as the United States, China, and leading European nations. However, gaps remain in fostering partnerships with underrepresented regions, emphasizing the need for a more globally integrated approach.

If we assess the quality of articles based on citation counts, five articles stand out as the most highly cited. The article with the highest number of citations (n = 2053) was published by Finnerup et al. in 2015 [28]. This publication presents the revised Neuropathic Pain Special Interest Group (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain, which were updated following a systematic review and meta-analysis of 229 randomized, double-blind studies. It underscores the modest efficacy of existing treatments for neuropathic pain while strongly recommending tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin as first-line therapies. Furthermore, it highlights a substantial unmet need due to inadequate treatment responses and limitations in clinical trials. The second most cited article (n = 1959) introduced the grading system (definite, probable, possible) for diagnosing neuropathic pain, developed by Treede et al. [29], which is based on neurological evidence and proposed for both clinical and research applications. Another highly cited article (n = 1933) by Rolke et al. [30] presented the standardized quantitative sensory testing (QST) protocol developed by the German Research Network on Neuropathic Pain (DFNS), which includes age- and gender-matched reference values to characterize somatosensory phenotypes in neuropathic pain patients, providing valuable insights into underlying mechanisms through precise sensory profiling. The fourth and fifth most highly cited articles (n = 1751 and 1630, respectively) were the paper presenting the development of the DN4 questionnaire by the French Neuropathic Pain Group [31] and the paper introducing the painDETECT screening tool [32], designed to identify neuropathic components in patients with low back pain.

The co-authorship analysis identified six distinct clusters, each exhibiting varying degrees of interconnectivity within the group but with no links connecting the clusters to one another. This finding underscores the presence of independent networks of researchers in the field, suggesting that each cluster operates as a separate aggregation of scientists with minimal collaboration across groups. Such a fragmented structure may indicate a lack of interdisciplinary exchange or communication between research teams, potentially limiting the broader dissemination of knowledge and innovation within the field. Encouraging stronger cross-cluster collaborations could foster a more integrated research community and promote a more unified approach to advancing the field. The largest cluster included Ralf Baron, Andrew S.C. Rice and Didier Bouhassira. One of the most influential articles from this group, cited nearly 600 times, described distinct neuropathic pain patterns using QST data from 902 patients (test cohort) and 233 patients (validation cohort) [33]. Through cluster analysis, three distinct sensory subgroups were identified. The first subgroup, characterized by sensory loss (42%), exhibited loss of small and large fiber’s function accompanied by paradoxical heat sensations. The second subgroup, representing 33% of the patients, was defined by thermal hyperalgesia, with preserved sensory function but heightened sensitivity to heat and cold, along with mild mechanical allodynia. The third subgroup, accounting for 24%, was characterized by mechanical hyperalgesia, involving small fiber loss, pinprick hyperalgesia, and dynamic mechanical allodynia. These subgroups were linked to specific etiologies, providing valuable insights into the relationship between sensory profiles and pathophysiological mechanisms. This classification has significant implications for clinical trial design, enabling the targeting of treatment-responsive populations and improving therapeutic outcomes.

The second cluster focused on Chinese authors, from Nanchang University, China. Their most prominent contribution to neuropathic pain research highlighted the role of adenosine triphosphate (ATP) as an extracellular signaling molecule acting via P2X and P2Y purinergic receptors expressed by satellite glial cells (SGCs) and macrophages [34]. They demonstrated how these cells, forming a macrophage-SGC-neuron triad in response to injury, release inflammatory cytokines and pro-nociceptive mediators, which enhance neuronal excitability and perpetuate inflammation-related neuropathic pain. A smaller cluster included Ghelardini C., from the University of Florence, Italy. Her scientific production on neuropathic pain was mainly focused on chemotherapy-induced neurotoxicity [35, 36] and diagnostic biomarker of peripheral neurotoxicity [37].

Another significant finding from our analysis was the identification of principal clusters derived from keyword co-occurrence analysis. These clusters offer valuable insights into the primary research themes and focal points within the field of neuropathic pain. By grouping frequently co-occurring keywords, the analysis highlights the interconnected areas of interest. The first identified cluster in the keyword co-occurrence analysis was centered on terms like "chronic pain," "prevalence," and "management," reflecting a strong research focus on understanding the treatment of neuropathic pain along with the evaluation of its real prevalence. Additionally, this cluster highlighted the prevalence of double-blind studies aimed at evaluating treatment efficacy, underscoring the commitment to evidence-based approaches in addressing these debilitating conditions. The keyword co-occurrence analysis revealed additional clusters that highlight the wide scope of research efforts in neuropathic pain. One cluster was centered on "model," emphasizing the use of animal models and experimental studies to investigate the mechanisms of neuropathic pain, including insights into spinal cord and peripheral nerve injuries. The most cited article (n = 527) on this topic, published by Nirmal Singh's group, provided a comprehensive review of approximately 40 animal models of neuropathic pain [38]. The study discussed their methodologies, behavioral characteristics, limitations, and advantages. These models have been instrumental in elucidating the peripheral and central mechanisms underlying chronic neuropathic pain and have significantly contributed to the development of novel therapeutic agents. However, the authors emphasized the importance of interpreting results within the specific context of each model, as variations in methodology can lead to significant differences in outcomes.

Another identified cluster centered on "expression," highlighting molecular and cellular research aimed at revealing the mechanisms underlying inflammation, oxidative stress, and the role of microglia and other critical proteins in the pathophysiology of neuropathic pain. According to the most cited article on this topic [39] (n = 209), microglia play a pivotal role in the development and persistence of neuropathic pain. Microglial activation is initiated in response to nerve injury, during which mediators such as Neuregulin-1, matrix metalloproteinases (MMP-2 and MMP-9), chemokine ligand 2 (CCL2), and fractalkine are released, further triggering and sustaining microglial activation. Activated microglia, in turn, release pro-inflammatory cytokines such as interleukin (IL)−6, IL-1β, and tumor necrosis factor-α (TNF-α), which enhance neuronal excitability and reduce inhibitory signals, contributing to the painful symptoms of neuropathic pain.

Another significant area of exploration highlighted the therapeutic potential of neuromodulation as a minimally invasive approach for managing neuropathic pain. This spectrum of interventions ranges from simpler techniques, such as pulsed radiofrequency (PRF) applied directly to targeted nervous tissues like the dorsal root ganglion (DRG) [40], to more advanced systems, including spinal cord stimulation (SCS) [41, 42] and dorsal root ganglion stimulation (DRGS) [43, 44]. However, the interconnected but distinct nature of the research clusters underscores the need for integrating findings across these domains to deepen the understanding and enhance the treatment of neuropathic pain. Integrating experimental, molecular, and clinical findings will be crucial for advancing the development of targeted interventions aimed at improving the quality of life for patients with neuropathic pain.

The main goal of a bibliometric study is to offer insights and strategic recommendations that can help shape and direct future research initiatives. Consequently, future research in neuropathic pain should focus on developing innovative and tailored therapeutic approaches to address the limitations of current treatments. Several agents, such as botulinum toxin A (BTX-A), ketamine, and mexiletine, have emerged as promising candidates for targeting specific pathways implicated in neuropathic pain. BTX-A is hypothesized to exert its analgesic effects through central mechanisms involving retrograde axonal transport [45]. It is now generally recommended as a third-line therapy for peripheral neuropathic pain due to its ability to modulate pain signals effectively. Mexiletine, an older anti-arrhythmic medication with sodium channel-blocking properties, has been repurposed for conditions such as primary erythromelalgia, a genetic disorder characterized by intense burning pain and vasomotor disturbances exacerbated by heat [46, 47]. This condition is associated with a gain-of-function mutation in Nav1.7 sodium channels, making mexiletine an effective therapeutic option [48]. Ketamine, an NMDA antagonist with potent analgesic properties, has demonstrated a statistically significant reduction in pain intensity when added to standard neuropathic pain treatments, both one week and 30 days after treatment. However, this benefit is counterbalanced by potential adverse effects, including increased discomfort and psychedelic symptoms [49]. Another notable candidate is ambroxol, traditionally used for its antitussive and anti-secretory effects. Ambroxol exhibits potent sodium channel-blocking activity by targeting Nav1.7 and Nav1.8 channels, coupled with anti-inflammatory properties [50]. These characteristics highlight its potential as a topical formulation for neuropathic pain management, offering a novel therapeutic option for patients.

Advances in neurostimulation techniques, including SCS, DRGS, and transcranial magnetic stimulation (rTMS), offer minimally invasive alternatives that act on central and peripheral mechanisms of pain. These modalities should be further refined through rigorous clinical trials to optimize stimulation parameters and expand their applications. Additionally, individualized therapeutic strategies based on patient stratification using biomarkers, sensory phenotyping, and genetic profiling can enhance treatment outcomes. Stratified approaches, as endorsed by regulatory guidelines, could link specific neuropathic pain profiles to targeted therapies, improving the precision of clinical trials and therapeutic interventions.

Emerging technologies, such as artificial intelligence (AI) and machine learning (ML), offer significant potential for analyzing large datasets and identifying patterns in treatment responses, thereby advancing the personalization of care in pain medicine [51]. These advancements are particularly promising for the minimally invasive management of neuropathic pain, where AI could optimize procedural strategies and enhance treatment outcomes [52]. However, while the integration of clinical data with AI systems holds tremendous potential, several ethical challenges, including data privacy, algorithmic transparency, and equitable access, must be addressed before such approaches can be broadly implemented in clinical practice [53]. Finally, fostering interdisciplinary collaborations and addressing existing research gaps in future studies will likely lead to the development of more effective and comprehensive therapeutic strategies for this challenging condition. A graphical representation of the proposed strategy to enhance both research studies and clinical management of neuropathic pain is illustrated in Fig. 9.

Proposed strategy for effective neuropathic pain management. This figure illustrates a comprehensive approach integrating new drug development, personalized therapeutic strategies based on patient stratification through biomarkers, sensory phenotyping, and genetic profiling. It emphasizes the importance of clinical data integration, advancements in neurostimulation techniques, and the application of artificial intelligence (AI) and machine learning (ML) models to optimize treatment outcomes for patients with neuropathic pain. Created with BioRender.com

Our bibliometric analysis has several limitations. First, the study was confined to articles retrieved exclusively from the WoSCC database, potentially excluding relevant studies indexed in other databases such as Scopus or PubMed, as well as grey literature sources. While WoSCC was selected for its reliability and widespread use in bibliometric research [54], this choice may have limited the comprehensiveness of our dataset. Second, bibliometric analyses inherently differ from systematic reviews or meta-analyses. Their purpose is to explore publication patterns, citation networks, and collaborative trends rather than to evaluate the quality or outcomes of specific studies [55]. Therefore, while our analysis provides a high-level overview of research trends in neuropathic pain, it does not replace in-depth evaluations of individual studies or treatment outcomes. Another limitation lies in the search strategy, which, despite being carefully designed, may not have fully captured all relevant publications on neuropathic pain. Although our comprehensive search initially identified a large volume of articles, many were excluded for irrelevance or duplication. This suggests that while the search strategy was effective in covering a significant portion of the indexed literature, some studies of importance might have been overlooked. Finally, temporal trends in publication activity may be influenced by external factors, such as variations in funding availability, regional research priorities, and evolving scientific interests. These factors could affect the representation of certain topics or geographic regions within the dataset. Additionally, since research is dynamic, bibliometric analyses should be periodically updated to reflect the latest developments in the field.