Introduction

Cancer remains one of the leading causes of morbidity and mortality worldwide, with its burden increasingly felt in low- and middle-income countries, including Nigeria. Beyond the direct effects of the malignancy itself, patients with cancer often endure a constellation of debilitating symptoms, among which pain is the most prevalent and distressing. It is estimated that up to 70–80% of patients with advanced cancer experience significant pain, substantially impairing quality of life, functional status, and psychological well-being [1]. While nociceptive pain has been extensively characterized, neuropathic pain (NP) represents a distinct and often underrecognized pain mechanism in the oncologic population.

NP results from direct injury or dysfunction of the somatosensory nervous system, commonly occurring in cancer patients due to tumour infiltration of nerves, nerve compression, or as a consequence of neurotoxic cancer therapies such as platinum-based chemotherapy, taxanes, and radiation [2–4]. Unlike nociceptive pain, NP is frequently refractory to conventional opioids, necessitating the use of adjuvant analgesics such as gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors [5]. The pathophysiology of NP is complex, involving peripheral and central sensitization, ectopic neuronal activity, and—crucially—a robust neuroinflammatory component. Increasing evidence suggests that systemic inflammation plays a pivotal role in the initiation and maintenance of NP, creating a bidirectional interaction between the immune system and the nervous system [6, 7].

The haematological profile of a patient, comprising parameters such as white blood cell (WBC) count, haemoglobin (Hb), neutrophil count, lymphocyte count, and platelet (PLT) count, serves as a readily available and cost-effective reflection of systemic inflammatory status. In recent years, composite inflammatory indices derived from these basic haematological parameters have gained prominence as surrogate markers of systemic inflammation in various disease states [8–10]. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been extensively studied as prognostic indicators in cancer, reflecting the balance between the innate inflammatory response (neutrophils) and adaptive immune regulation (lymphocytes). The systemic immune inflammation index (SII), calculated as PLT × neutrophil/lymphocyte, integrates three major immune cell lineages and has been proposed as a more comprehensive marker of systemic inflammation [11, 12]. Similarly, the neutrophil-platelet score (NPS) and haemoglobin-to-platelet ratio (HPR) have emerged as useful indices in predicting outcomes in malignancies and inflammatory conditions [13, 14].

The rationale linking these haematological indices to NP lies in the central role of inflammation in pain pathogenesis. Neutrophils, as first responders to tissue injury and inflammation, release pro-inflammatory cytokines, chemokines, and reactive oxygen species that can sensitize peripheral nociceptors and promote neuroinflammation. Elevated neutrophil counts, therefore, may reflect heightened systemic inflammatory activity capable of driving NP mechanisms [15]. Conversely, lymphocytes are critical for immune regulation, and a relative lymphopenia—as reflected in elevated NLR—may indicate impaired anti-inflammatory or immunomodulatory capacity, allowing unchecked neuroinflammation [16]. PLTs, beyond their well-established role in haemostasis, are increasingly recognized as key mediators of inflammation, releasing a plethora of pro-inflammatory mediators including serotonin, PDGF, and various chemokines that can modulate neuronal excitability and pain signalling. Thus, the composite indices that capture the interplay between these cell populations may serve as integrated biomarkers of the inflammatory milieu that contributes to NP.

Anaemia, reflected by reduced Hb levels, is common in cancer patients and has been independently associated with pain severity in several studies. The mechanisms linking anaemia to NP are multifactorial and may involve tissue hypoxia, altered oxygen delivery to peripheral nerves, and the systemic inflammatory response that often accompanies cancer-associated anaemia [17, 18]. The HPR, which combines two parameters with opposing inflammatory and functional roles, may offer a nuanced perspective on the balance between oxygen-carrying capacity and inflammatory thrombocytosis.

Despite the growing body of evidence implicating systemic inflammation in NP pathogenesis, studies exploring the direct association between haematological indices and NP in cancer patients remain limited. In the Nigerian context—where cancer burden is rising, resources for comprehensive pain assessment are constrained, and access to advanced diagnostic modalities remains challenging—the identification of simple, cost-effective, and readily available biomarkers for NP could have significant clinical utility. Such biomarkers could facilitate earlier identification of patients at risk for NP, guide targeted therapeutic interventions, and improve pain management outcomes in resource-limited settings.

In this study, we aim to explore the association between haematological parameters—including WBC, Hb, neutrophil count, lymphocyte count, PLT, and composite inflammatory indices such as NLR, PLR, SII, NPS, and HPR—and NP in Nigerian cancer patients. By elucidating these relationships, we hope to contribute to the growing understanding of the inflammatory underpinnings of NP and to identify potential haematological markers that may aid in the risk stratification and management of this challenging pain syndrome in cancer patients.

Materials and methods

This cross-sectional study was conducted at the University of Ilorin Teaching Hospital and included adult patients with solid cancers attending the outpatient oncology clinics and palliative care services. The study received ethical approval from the institution’s Ethics Review Committee (UITH/CAT/189/21/384). All participants provided written informed consent after receiving a full explanation of the study. Study participants comprised adult cancer patients attending the institution who met the following eligibility criteria: (i) age 18 years or older; (ii) a confirmed medical diagnosis of cancer; and (iii) adequate cognitive function to complete the questionnaire, as evidenced by the ability to respond to simple orientation questions (e.g., name, age, time of day). Participants were recruited using serial sampling. Eligible patients completed a self-administered questionnaire capturing sociodemographic and clinical characteristics, including age, gender, educational level, occupation, and marital status. Clinical data comprising cancer type, treatment history, social history, comorbidities, and performance status were obtained through medical record review and patient interviews. Of the 126 cancer patients initially recruited, 36 were excluded from the final analysis due to incomplete full blood count results, which. Consequently, the remaining 90 patients with complete data comprised the final study cohort available for statistical evaluation.

Results

A total of 90 patients were enrolled in this study from an initial 126 patients. All participants provided informed consent and completed all questionnaire items without omission. The mean age of the cohort was 51.83 ± 13.42 years (Table 1). The study population was predominantly female (80%), with a substantial proportion being married (81.1%) and having attained tertiary education (42.2%). The mean NRS score for the presenting pain was 2.66 ± 1.98, with the majority of patients (87.8%) reporting some degree of pain. Mild pain was reported by 57.8% of patients, moderate pain by 27.8%, and severe pain by 2.2%. For average pain, the score was 3.49 ± 2.15, with 51.1% having mild pain, 43.3% having moderate pain, and 3.3% having severe pain. Using the PD-Q, the mean pain score was 8.20 ± 4.80. Based on PD-Q scores, 21.1% of the study population exhibited evidence of NP (score ≥ 13). The majority (> 50%) of the patients had symptoms of NP except for the cold/ heat (31%) symptoms (Figure 1).

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Figure 1. Percentage of patients that had each neuropathic pain symptom.

Pain management in this cohort was predominantly pharmacological; all patients were receiving analgesic therapy, with the majority (90%) prescribed paracetamol either alone or in combination. NSAID use was 27.8%; weak opioids (dihydrocodeine, tramadol) were utilized by 16.7% of patients, while 34.4% were on strong opioids. Notably, only 7.8% were receiving medications specifically indicated for NP, such as pregabalin.

The haematological parameters showed that Hb was significantly associated with NP (p = 0.006); likewise, the ALC (p = 0.003) and the PLR (p = 0.015) also showed significant associations. The other data are shared in Table 2. The Spearman’s rank correlation test was employed to explore the associations between haematological indices and key pain features, allowing for a bivariate analysis of the CBC parameters against the clinical dimensions of pain. With respect to pain features, none of the CBC parameters showed significant associations with presenting pain, and only the NLR was significantly associated with the average pain in 4 weeks (data not shown). By contrast, a distinct pattern emerged in relation to performance status: PLT, ANC, NLR, PLR, SII, and the HPR all demonstrated significant positive correlations with the Karnofsky performance status (p < 0.05). With regard to the NP symptoms, Hb was significantly correlated with burning sensation, tingling sensation, and electric shock-like pain; PLT were with light touch; ANC was with electric shock-like pain; ALC was with tingling sensation and numbness; NLR was with burning sensation, tingling sensation, and electric shock-like pain; PLR was with tingling sensation and electric shock-like pain; SII was with burning sensation, tingling sensation and electric shock-like pain; NPS was with burning sensation, electric shock-like pain and numbness; HPR was with electric shock-like pain (p < 0.05). The results are shown in Table 3. Correlation analysis showed NP positively correlated with PLT count (ρ = 0.230, p = 0.029), ANC (ρ = 0.263, p = 0.012), NLR (ρ = 0.248, p = 0.019), SII (ρ = 0.215, p = 0.045), and NPS (ρ = 0.248, p = 0.018), while correlating negatively with Hb (ρ = –0.223, p = 0.034) (Table S1).

The Binary logistic regression analysis revealed that Hb (p = 0.01), PLTs (p = 0.014), ALC (p = 0.007), ANC (p = 0.045), NLR (p = 0.021), and HPR (p = 0.003) each independently predicted the presence of NP in the cancer patient cohort (Table 4).

Discussion

This study sought to explore the association between haematological parameters—including CBC components and derived inflammatory indices—and NP in a cohort of Nigerian cancer patients. The findings reveal that several haematological markers, particularly those reflecting systemic inflammation, are significantly associated with the presence of NP. These results align with the growing body of evidence implicating neuroinflammation in the pathogenesis of NP and suggest that simple, cost-effective haematological indices may serve as useful adjuncts in identifying cancer patients at risk for this debilitating pain syndrome.

The prevalence of NP in this study, as determined by the PD-Q, was 21.1%. This figure is consistent with previous reports in mixed cancer populations, where NP prevalence ranges from 20% to 40%, depending on tumour type, disease stage, and diagnostic criteria employed [19, 20]. The relatively lower prevalence observed in our cohort may reflect the under-recognition of NP in routine clinical practice. Notably, despite this prevalence, only 7.8% of patients were receiving medications specifically indicated for NP, such as pregabalin, underscoring a significant treatment gap that warrants clinical attention.

A central finding of this study is the consistent association between markers of systemic inflammation and NP. In bivariate correlation analysis, PLT, ANC, NLR, PLR, SII, NPS, and HPR all demonstrated significant correlations with NP and its constituent symptoms. These associations persisted in multivariate logistic regression, where Hb, PLTs, ALC, ANC, NLR, and HPR emerged as independent predictors of NP. Collectively, these findings support the hypothesis that systemic inflammation plays a pivotal role in the pathophysiology of NP and some other chronic conditions.

The observed positive correlations between neutrophil-related indices (ANC, NLR, SII, NPS) and NP are biologically plausible. Neutrophils are among the first responders to tissue injury and inflammation, releasing a cascade of pro-inflammatory cytokines which includes IL-1β, tumour necrosis factor-α (TNF-α), and IL-6—as well as chemokines and reactive oxygen species that can sensitize peripheral nociceptors and promote central sensitization with associated hyperalgesia [21–23]. In the context of cancer, tumour-derived factors may further amplify this neutrophilic response, creating a pro-inflammatory milieu conducive to the development and maintenance of NP [24–26]. A recent study demonstrated that inhibiting neutrophil differentiation and maturation can help alleviate inflammatory pain hypersensitivity caused by neutrophils [27]. On the other hand, the NLR, which captures the balance between neutrophilic inflammation and lymphocytic immune regulation, has been extensively studied as a prognostic marker in cancer [9, 28–30]. Our finding that elevated NLR is associated with NP extends this utility, suggesting that the NLR may serve as a dual-purpose biomarker, reflecting both oncologic prognosis and pain phenotype.

PLTs also emerged as key correlates of NP in our study. Elevated PLT and PLR were significantly associated with NP, a finding that aligns with the emerging recognition of PLTs as mediators of neuroinflammation [31]. Beyond their canonical roles in haemostasis and thrombosis, PLTs are increasingly understood to be active participants in inflammatory processes, releasing a rich array of mediators—including serotonin, PLT-derived growth factor (PDGF), and various chemokines—that can modulate neuronal excitability, promote glial activation, and contribute to pain sensitization [32, 33]. Thrombocytosis, commonly observed in malignancy as a paraneoplastic phenomenon [34], may therefore represent not merely a marker of systemic inflammation but an active contributor to NP pathogenesis.

The SII, which integrates PLT, neutrophil, and lymphocyte counts into a composite index, demonstrated significant associations with NP and its symptoms, including burning sensation, tingling, and electric shock-like pain. As a more comprehensive measure of systemic immune-inflammatory status, SII may capture synergistic interactions among these cell populations that are not fully reflected in simpler indices [35]. Our results suggest that SII warrants further investigation as a potential biomarker for NP risk stratification.

Anaemia, reflected by reduced Hb, was significantly associated with NP, with lower Hb levels correlating with greater NP likelihood. This finding is consistent with previous studies linking anaemia to quality of life in cancer patients [36]. The mechanisms underlying this association are multifactorial. Anaemia may contribute to tissue hypoxia, compromising oxygen delivery to peripheral nerves and exacerbating nerve injury. Additionally, anaemia in cancer patients often reflects underlying chronic inflammation, with inflammatory cytokines suppressing erythropoiesis and promoting hepcidin-mediated iron sequestration [37]. Interestingly, painkillers like diclofenac, though they attenuate acute phase reactants, have been shown to amplify the expression of hepcidin in cancer [38]. This could have been another cause of anaemia in our study. Thus, low Hb may serve as a surrogate marker of systemic inflammation rather than a direct cause of NP. The HPR, a composite index combining Hb and PLTs, was among the strongest independent predictors of NP in our regression analysis, suggesting that the interplay between oxygen-carrying capacity and inflammatory thrombocytosis may be particularly relevant to NP pathogenesis.

Interestingly, none of the haematological parameters demonstrated significant associations with presenting pain intensity, suggesting that these markers may be more closely linked to the neuropathic quality of pain, thus reflecting underlying neuroinflammatory mechanisms rather than acute pain severity. This distinction supports the conceptualization of NP as a distinct pain entity with unique pathophysiological underpinnings that may be captured by systemic inflammatory markers.