Neuralgia is a type of pain resulting from damage or disease in the nervous system. The International Association for the Study of Pain defines neuropathic pain as pain caused by a lesion or dysfunction of the somatosensory system, which may involve the peripheral or central nervous system (International Association for the Study of Pain, 2025). Unlike nociceptive pain, which results from direct tissue injury, neuropathic pain originates from abnormal nerve signaling, often occurring in the absence of external stimuli (Bernetti et al., 2021). This type of pain can be persistent or episodic and may severely compromise the patient’s quality of life and psychological wellbeing.

Preventing neuralgia requires addressing underlying conditions, minimizing nerve injury, and ensuring rational drug use (Bannister et al., 2020). Although drug-induced neuralgia is relatively rare, it presents unique challenges owing to its often delayed onset and nonspecific symptoms (Yao et al., 2025; Merheb et al., 2022). Typically characterized by sharp, burning, or shooting pain, it may be misdiagnosed in its early stages, complicating timely intervention (Li and Liu, 2025). Among the various etiologies of neuropathic pain, chemotherapeutic agents are prominent contributors due to their neurotoxic effects (Etminan et al., 2014). Other recognized causes include certain antiviral agents and antibiotics (Han et al., 2023). Although treatments such as antidepressants, gabapentinoids, sodium channel blockers, TRPV1 agonists, and opioids are available, managing neuropathic pain remains challenging, due to interindividual variability in treatment response and an incomplete understanding of the underlying pathophysiological mechanisms (Baranidharan et al., 2023). Therefore, its pathophysiology underscores the critical need for further investigation (Jensen et al., 2011).

We conducted a pharmacovigilance study using data from the FAERS. FAERS serves as a vital resource in pharmacovigilance, facilitating the identification of potential drug-related adverse drug events (ADEs) through post-marketing surveillance. The database contains voluntarily submitted reports from healthcare professionals and consumers, offering valuable information on demographic characteristics, drug exposure, clinical outcomes, and more (Bousquet et al., 2005). Through systematic analysis of this database, we can identify disproportionality signals, which are statistical indicators suggesting a higher-than-expected frequency of a specific ADE associated with a particular drug (Fusaroli et al., 2024; Almenoff et al., 2007).

The objective of this study was to identify pharmacological agents potentially associated with drug-induced neuralgia by performing disproportionality analysis of the FAERS database. The findings aim to support clinicians in recognizing high-risk medications, inform future research directions, and ultimately enhance the management of neuralgia in patients receiving pharmacotherapy.

Neuropathic pain arises from various causes, including nerve trauma, compression, vascular and neurological diseases, infections, metabolic disorders, medications, and hereditary conditions (Jones et al., 2020). It is a complex condition resulting from nervous system damage or dysfunction and is commonly associated with diabetes mellitus, infections, and nerve trauma (Besi et al., 2015). However, certain medications can also induce neuropathic pain through mechanisms such as direct neurotoxicity, mitochondrial dysfunction, immune-mediated responses, and metabolic imbalances that impair nerve function (Zhuo et al., 2011). The severity and persistence of symptoms depend on multiple factors, including drug type, dosage, treatment duration, and patient susceptibility (Guo et al., 2024). Notably, a study in Taiwan identified renal disease as a predisposing factor for ethambutol-induced optic neuropathy, underscoring the role of underlying conditions in drug-induced neurotoxicity (Chen et al., 2012). Given its significant clinical impact, drug-induced neuropathic pain necessitates early recognition and intervention to minimize patient burden. A thorough understanding of the mechanisms and risk factors associated with neurotoxic medications enables clinicians to optimize treatment strategies while mitigating adverse effects. Future research should prioritize the development of neuroprotective approaches to prevent or reduce the risk of drug-induced neuropathy.

The results of this study indicate a continuous annual increase in adverse event reports related to drug-induced neuralgia, peaking in 2022. This trend may be attributed to multiple factors, including the growing use of medications, heightened public awareness of adverse reactions, regulatory and policy changes, advancements in medical technology, and improved data sharing and transparency (Baah, 2020). These factors collectively contribute to the rising number of reported cases. Furthermore, the findings suggest that the incidence of drug-induced neuropathic pain is significantly higher in females than in males. Although clinical observations do not indicate substantial sex-based differences in responses to analgesic medications, research on sex differences in neuropathic pain remains limited (Salis et al., 2024). Notably, variations in neuropathic pain intensity have been documented in diabetic patients, with females generally reporting higher pain sensitivity and intensity than males (Abraham et al., 2018). Moreover, sex-related differences may influence responses to certain analgesics, often necessitating dose adjustments or alternative pain management strategies (Marcianò et al., 2024). Hormonal fluctuations in females may further affect pain perception and treatment efficacy, highlighting the need for more targeted research in this area.

Lenalidomide, used to treat multiple myeloma and lymphoma, can cause peripheral neuropathy, though less frequently than thalidomide. Symptoms include numbness, tingling, and pain in the extremities (Cao et al., 2022). Its neurotoxicity may stem from mitochondrial dysfunction, oxidative stress, or immune-related mechanisms (Deng et al., 2021; Stino et al., 2024). Regular monitoring is essential, and dose adjustments or supportive treatments like vitamin B supplementation may help manage symptoms (Dalla Torre et al., 2016). Early detection and intervention can improve patient outcomes. Sodium citrate serves as an anticoagulant, preservative, and pH regulator, with widespread applications in both the food industry and medical field (Shvetsova et al., 2024). Studies have demonstrated that in sustained low-efficiency dialysis, sodium citrate provides effective regional anticoagulation without affecting systemic coagulation function, offering a viable alternative for clinicians (Zhang et al., 2013). Additionally, research indicates that using a 4% sodium citrate solution as a locking agent for central venous catheters in ICU patients is safer than heparin, as it reduces the risk of bleeding and catheter occlusion without increasing the incidence of hypocalcemia or infections (Deng et al., 2023). Furthermore, sodium citrate has been shown to inhibit cancer cell metabolism, suppressing proliferation and enhancing chemotherapy efficacy (Icard et al., 2024; Yin et al., 2025). It also improves immune cell function by increasing glucose availability, thereby promoting an antitumor immune response, suggesting its potential role as an adjuvant in immunotherapy (Wu et al., 2024).

Drug-induced neuralgia, a type of neuropathic pain resulting from medication-related nerve damage, is a critical concern in clinical practice (Si et al., 2018). Among the most commonly implicated drug classes are chemotherapeutic agents, antibiotics, and immunosuppressants, each of which causes nerve injury through distinct biological mechanisms (van Velzen et al., 2020). Understanding these mechanisms is essential for developing effective preventive and therapeutic strategies. Chemotherapeutic agents, particularly platinum-based drugs such as cisplatin and oxaliplatin, taxanes such as paclitaxel and docetaxel (Tian et al., 2025), and vinca alkaloids such as vincristine, are known to cause peripheral neuropathy (Ye and Abdi, 2025). These drugs induce nerve damage through mitochondrial dysfunction, oxidative stress, and microtubule disruption, leading to impaired neuronal function and persistent pain (Sisignano et al., 2014). Similarly, certain antibiotics, including aminoglycosides such as gentamicin and amikacin, polymyxins, and fluoroquinolones such as ciprofloxacin, have been associated with neurotoxicity (Kuehn, 2013). These antibiotics can disrupt neuronal membranes, interfere with ion channel function, and hinder neuronal repair, with the severity of neuralgia often correlating with the dosage and duration of treatment (Rezaei et al., 2018). Furthermore, immunosuppressants, particularly biologic agents targeting tumor necrosis factor-alpha, may contribute to neuropathic pain by altering immune responses and triggering neuroinflammation. Prolonged use can further impair nerve repair mechanisms and exacerbate neural damage, increasing the risk of persistent pain (Lallana and Fadul, 2011).

Overall, drug-induced neuralgia is a multifactorial condition driven by neurotoxic, immune-mediated, and metabolic disturbances. Recognizing the mechanisms by which different drug classes contribute to neuropathic pain is essential for minimizing risks, guiding clinical decisions, and improving patient outcomes.

The FAERS database plays a crucial role in drug safety research but has notable limitations. It relies on voluntary reporting, leading to reporting bias and underreporting of certain adverse events. The lack of exposure data prevents accurate risk estimation, and data quality issues, including missing or inconsistent information, further complicate analysis. FAERS cannot establish causal relationships due to potential confounding factors, and media influence may amplify reporting. Duplicate reports, delayed data updates, and limitations in adverse event classification also affect reliability. Additionally, most data come from the U.S. and other high-income countries, reflecting differences in healthcare systems and reporting habits. This may limit how well our findings apply to low- and middle-income countries and may not reflect the global burden of drug-induced neuralgia. We recommend future pharmacovigilance efforts include more diverse international data to improve fairness and accuracy.

This study analyzed the FAERS database to identify drugs associated with neuralgia. Chemotherapy drugs, certain antibiotics, and immunosuppressants were major triggers, likely causing nerve damage through neurotoxicity, immune responses, or metabolic disturbances. The findings indicate a higher prevalence in women. In terms of indications, multiple myeloma and multiple sclerosis were the most frequently reported. The study highlights the importance of early monitoring and rational drug use. These insights provide guidance for future research and clinical practice.