Our study showed the general characteristics, pain and related factors of patients who referraled to Palliative care service of advanced NSCLC patients. It is a relatively rare description on the characteristics of pain caused by a certain cancer. In addition to reflecting patient's pain features, we try to find some indicators and factors that can reflect patient's pain frequency and its’ severity in clinical data such as inflammatory markers, related symptom severity. Our study confirmed that the clinical manifestations of pain in NSCLC patients were correlated with bone metastasis, metastasis with more than two sites, elevated CRP, and the EGFR-TKI usage. Whether there is a certain potential connection between these factors deserves to be further studied.
Of all 95 included patients, 54 patients (56.7%) reported cancer pain suffering. Of 54 patients with pain, there were 23 patients (42.6%) who suffered from severe pain (score > = 7) at the admission of PC. The incidence of pain in lung cancer patients was reported quite differently. It may be due to different baseline conditions of patients, different research background, etc. Prevalence of pain in the early stages of lung cancer has been reported to be as high as 56% [11]. Over 90% of patients with advanced lung cancer experienced pain and fatigue in another research [12]. In another study of patients with NSCLC, pain was reported to be only 37% [13]. These studies were quite heterogeneous with differences in sample sizes, cancer stage and clinical variables, making it difficult to ascertain the exact prevalence of pain among advanced lung cancer patients.
In our patients’ baseline, at the time of admission to PC, 60% of patients had been confirmed combined with bone metastasis. Approximately 40% of NSCLC patients developed bone metastases in their disease course [14]. Previous studies have testified that bone metastases strongly affected presence of cancer pain[15]. Bone pain was thought to be related with stimulation of sensory fibers distributed in the periosteum. Osteodynia was also known as related with prostaglandins, endothelins, nerve growth factors or inflammatory cells, and maybe the activation of several acid sensing receptors by local tissue acidosis[16,17]. The presence of bone metastasis also affects the pain distribution of NSCLC patients. Bone metastases sites of lung cancer are most common in the lumbar spine, pelvis, thoracic spine and ribs. In our research, the most frequent pain location was chest (n = 22), followed by dorsum (n = 11). The incidence of dorsum is high in patients, which may be related to the proportion of bone metastasis of our patients.
With the development of targeted therapy, more patients have done the corresponding gene detection before receiving systematic treatment. There was no significant correlation between EGFR mutation status and pain characteristics in our research but patients used EGFR-TKI reported lower pain intensity with statistical differences. Previous research also showed that EGFR-TKI strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. The PI3K/AKT/mTOR pathway and upregulated mitogen-activated protein kinase (MAPK) expression maybe involved in enhancement of nociception by activation of EGFR [18]. No EGFR-TKI usage, together with smoking, histological subtype and performance status were shown as associated with bone metastasis’ skeletal-related events (SRS) [19]. The systemic effect and mechanism of EGFR mutation and EGFR-TKI usage, their relationship with bone metastasis and pain characteristics are worth of further study.
C reactive protein (CRP), together with inflammation markers were testified to be related with pain manifestaion in previous research [20, 21]. Among breast cancer patients, women with pain detected higher CRP levels before anticancer treatment than women without pain[22]. It was reported that systemic inflammation maybe linked CP, but the relationship between pain and systemic inflammation in cancer was less well understood [23, 24
]. The current findings suggest a potential association between pain and inflammatory processes in NSCLC patients, with potential attention for future research and treatment strategies.