Identifying neuropathic pain and the effects of perioperative psychological intervention in patients with gastric cancer

Abstract

BACKGROUND

Patients with gastric cancer (GC) often experience complex pain, including a neuropathic component, which may influence their response to perioperative interventions.

AIM

To identify neuropathic pain (NP) components in patients with GC and evaluate the clinical efficacy of perioperative psychological interventions.

METHODS

The study comprised 100 patients with GC who underwent surgical treatment at Jiujiang No. 1 People’s Hospital between April 2022 and April 2025. Using randomized number tables, the participants were allocated into either an observation (n = 50) or control (n = 50) group. The control group received conventional perioperative pain management, while the observation group received additional perioperative psychological interventions. Between-group differences were compared in terms of pain intensity, pain characteristics, anxiety and depression levels, postoperative analgesic consumption, early postoperative recovery, and recovery quality.

RESULTS

On postoperative day 7, both groups exhibited higher Numeric Rating Scale scores for resting and activity pain than that demonstrated on preoperative day 1 (P < 0.05), while Hospital Anxiety and Depression Scale (HADS)-Anxiety and HADS-Depression scores were also lower (P < 0.05). Regarding the primary outcomes, patients in the observation group exhibited lower Numeric Rating Scale scores for resting and activity-related pain and a lower NP-positivity rate than those in the control group (P < 0.05). For the secondary outcomes, patients in the observation group had fewer effective presses for intravenous patient-controlled analgesia, lower morphine equivalents, earlier time to first ambulation, earlier time to first flatus, shorter hospital stays, and higher Quality of Recovery-15 scores compared with the control group (P < 0.05). Moreover, their HADS-Anxiety and HADS-Depression scores were also lower than those in the control group (P < 0.05). Stratified regression analysis revealed significant main effects of group assignment and NP status (P < 0.05), with a significant interaction term between group assignment and NP status (P < 0.05).

CONCLUSION

Effective identification of the NP component in the patients’ pain, coupled with perioperative psychological interventions, significantly reduced pain intensity and NP-positivity rates. This approach improved anxiety and depressive symptoms, decreased postoperative analgesic use, accelerated early recovery, and enhanced quality of recovery.

Key Words: Gastric cancer; Pain; Neuropathic; Perioperative; Psychological intervention

Core Tip: Neuropathic pain (NP) components are common but often overlooked in patients undergoing surgery for gastric cancer. Identifying NP components and combining standard perioperative pain management with psychological interventions can significantly alleviate pain intensity, reduce NP positivity, improve emotional well-being, and decrease analgesic consumption. Moreover, such identification accelerates postoperative recovery and enhances overall recovery quality, emphasizing the clinical value of integrating psychological care into perioperative pain management.

INTRODUCTION

Among malignant tumors, gastric cancer (GC) has high incidence and mortality rates globally. Over 70% of patients with mid-to-late stage GC experience moderate to severe pain, with approximately 30%-50% of these patients exhibiting neuropathic pain (NP) components[1,2]. NP arises from direct damage to or from disease effects on the somatic sensory nervous system. Its pathogenesis involves multidimensional pathophysiological alterations, including peripheral sensitization, central sensitization, dysregulation of descending inhibitory pathways, and neuroimmune interactions[3,4]. In the context of GC, tumor infiltration compressing the nerve plexuses, nerve injury from surgical trauma, and the neurotoxic effects of chemotherapeutic agents can induce complex NP, which is distinctly different from simple nociceptive pain[5,6]. Therefore, accurately identifying the NP component within pain experiences among patients with GC and implementing targeted psychological interventions during the perioperative period are crucial for pain management. We examined 100 patients with GC who underwent surgical treatment at Jiujiang No. 1 People’s Hospital between April 2022 and April 2025. This study investigated the identification of NP components within patients’ pain experiences and evaluated the clinical efficacy of perioperative psychological interventions. This study aimed to provide scientific evidence for clinical practice, thereby enhancing pain relief outcomes and quality of life for patients.

MATERIALS AND METHODS

Study population

Following approval by Ethics Committee of Jiujiang No. 1 People’s Hospital, 100 patients with GC who underwent surgical treatment at Jiujiang No. 1 People’s Hospital between April 2022 and April 2025 were enrolled.

Sample size estimation

Based on prior literature and anticipated effect size, with α = 0.05 (two-tailed), β = 0.20 (80% test power), and accounting for a 20% dropout rate, the final sample size was determined as 100 cases. Inclusion criteria comprised patients: (1) Aged 18-75 years; (2) With pathologically confirmed primary GC; (3) Had undergone laparoscopic radical gastrectomy; (4) Had chronic pain persisting for ≥ 3 months preoperatively; (5) Were conscious and alert, with basic communication and comprehension abilities to complete questionnaire assessments; and (6) Voluntarily participated and signed an informed consent form. Exclusion criteria comprised patients with: (1) A history of severe cognitive impairment or psychiatric disorder; (2) Concurrent severe chronic pain conditions, such as lumbar disc herniation or postherpetic neuralgia; (3) Long-term high-dose opioid use or history of substance abuse preoperatively; (4) Severe cardiac, pulmonary, hepatic, or renal failure, or other surgical contraindications; (5) An expected survival of < 6 months; and (6) An inability to cooperate with the study protocol. Patients were randomized into an observation group (n = 50) and a control group (n = 50) using a random numbers table. Baseline characteristics were comparable between the groups (P > 0.05; Table 1).

Table 1 Comparison of general data, n (%)/mean ± SD.

Group	n	Sex		Age (years)	BMI (kg/m2)	TNM stage
		Male	Female			II	III	IV
Observation	50	32 (64.00)	18 (36.00)	62.41 ± 7.75	22.54 ± 1.86	8 (16.00)	36 (72.00)	6 (12.00)
Control	50	29 (58.00)	21 (42.00)	61.83 ± 7.58	22.77 ± 1.94	10 (20.00)	33 (66.00)	7 (14.00)
χ2/t		0.407		0.378	0.605	0.431
P value		0.523		0.706	0.547	0.806

BMI: Body mass index; TNM: Tumor-node-metastasis.

The target parameter for the power calculation was the between-group difference in the Numeric Rating Scale (NRS) for activity-related pain on postoperative day 7, as this variable best reflects the combined benefit of pharmacological and psychological interventions. Based on our pilot work (n = 20 per arm), we observed mean ± SD NRS scores of 5.8 ± 1.4 and 4.7 ± 1.2 in the control and intervention groups, respectively (Δ = 1.1). These values were consistent with the 1.0-1.3-point clinically relevant difference reported by Gerbershagen et al[7] in abdominal-oncology surgery. Using two-sided α = 0.05, power = 0.80, and assuming equal variances, the required sample size per group was calculated as follows: n = 2 × (Zα/2 + Zβ)² × σ²/Δ² = 2 × (1.96 + 0.84)² × 1.4²/1.1² = 42 patients per arm. Anticipating a 15% loss to follow-up (dropout, withdrawal of consent, or protocol violation), we increased the number to 50 patients per arm (n = 100). All calculations were performed using PASS 1 software.

Research methods

Conventional perioperative pain management for control group: Patients in the control group received the following conventional perioperative pain management. Preoperative phase: In accordance with the Chinese Expert Consensus on Perioperative Pain Management for Cancer Patients (2020 Edition), pain health education was conducted via verbal instructions and distribution of information leaflets detailing the usage and precautions for analgesic pumps. Intraoperative phase: General anesthesia was combined with postoperative intravenous patient-controlled analgesia (PCA). The drug formulation comprised sufentanil 2 μg/kg + tropanol 10 mg/100 mL saline solution, with a background rate of 2 mL/hour, a single bolus dose of 0.5 mL, and a lockout period of 15 minutes. Postoperative phase pain levels were assessed at regular intervals. Nonsteroidal anti-inflammatory drugs such as paracetamol sodium or weak opioids such as tramadol were administered on demand to supplement postoperative intravenous PCA. Concurrently, routine nursing measures, including wound care and early mobilization guidance, were implemented.

Perioperative psychological intervention protocol for the observation group: Patients in the observation group received the same conventional perioperative pain management as those in the control group along with a structured perioperative psychological intervention protocol. Details concerning the psychological intervention were as follows. Intervention team composition: A dedicated perioperative psychological intervention team was established consisting of one psychiatrist, one psychological counsellor, and two pain management nurses. This team was fully responsible for conducting systematic psychological assessments and delivering standardized interventions to the patients in the observation group. Preoperative phase (from admission to one day prior to surgery): The intervention team conducted face-to-face interviews with the patients to comprehensively evaluate their pain levels (using the NRS) and psychological status [using the Hospital Anxiety and Depression Scale (HADS)]. During the interviews, the team also explored patients’ perceptions of their illness and surgery, identified their key concerns (e.g., fear of pain, surgical risks, and cancer prognosis), and clarified their psychological needs. Cognitive behavioral therapy sessions, two personalized cognitive behavioral therapy sessions were provided, each lasting 60 minutes. The core contents included the following: Guiding patients to conduct cognitive restructuring, helping them identify and challenge catastrophic thinking related to pain (e.g., “postoperative pain will be unbearable”), surgery (e.g., “the surgery will definitely fail”), and cancer (e.g., “cancer means death”).

Assisting patients in establishing rational expectations regarding perioperative pain (e.g., “postoperative pain can be effectively controlled with proper management”), the surgical process (e.g., “laparoscopic surgery has less trauma and faster recovery”), and recovery progress (e.g., “it takes about 1-2 weeks to return to basic daily activities”). Encouraging patients to engage in moderate preoperative activities (e.g., bedside walking for 10-15 minutes twice daily, and slow deep breathing exercises) to break the vicious cycle of “pain-avoidance-functional decline”. Instructing patients on relaxation techniques, including progressive muscle relaxation and guided imagery. They were provided with audio materials for practice, with each training session lasting 30 minutes and conducted once daily until the day prior to surgery.

Early postoperative phase (postoperative days 2-3): The intervention team conducted daily bedside visits to provide supportive psychological intervention, with each interaction lasting 20-30 minutes. Technique reinforcement: A focus was placed on reinforcing the application of cognitive behavioral intervention techniques learned preoperatively. For example, when patients reported pain, the team guided them to recall the pain and applied cognitive restructuring methods to alleviate pain-related negative thoughts. Emotional expression and pain coping guidance: Patients were encouraged to openly express their pain sensations and emotional states (e.g., anxiety and frustration). When pain intensified, particularly before dressing changes or functional exercises, or when patients’ self-perceived pain worsened, the team guided them to actively apply relaxation techniques (progressive muscle relaxation, guided imagery) learned preoperatively to relieve pain and emotional tension.

Recovery phase (from postoperative day 4 to discharge): A cognitive behavioral consolidation session lasting 45 minutes was conducted. The session focused on guiding patients to review the pain management strategies that were effective during their recovery (e.g., which relaxation technique worked best for relieving pain and how cognitive restructuring helped reduce anxiety) and reinforcing these effective strategies. Peer support group participation: Patients participated in peer support groups consisting of individuals with similar GC-related conditions. During the group sessions (conducted in a ward meeting room, duration 60 minutes), patients were encouraged to share their experiences in pain management and rehabilitation, which helped enhance their self-efficacy and expand their social support networks. Post-discharge plan development: This involved collaboratively developing a personalized post-discharge pain management and activity plan for patients. The plan included: Continuing relaxation training (30 minutes per session, once daily). Gradually increasing activity levels (e.g., starting with 15-minute walks at home and gradually extending to 30 minutes as tolerated). Establishing clear guidelines for identifying and responding to potential pain recurrence (e.g., when to use over-the-counter analgesics and when to contact the hospital).

Observation indicators

The differences between the two patient groups were compared in terms of pain intensity, pain characteristics, anxiety and depressive mood, postoperative analgesic consumption, early postoperative recovery, and recovery quality. Data collection and assessments were conducted by two pain specialists who had undergone standardized training. These specialists were blinded to the randomization of the study and did not participate in the group allocation or intervention.

Pain intensity

Resting and activity-related pain were assessed using the NRS[8] on day 1 preoperatively and postoperatively on day 7. The scale ranged from 0 (representing no pain) to 10 (representing unbearable pain). Higher scores indicated greater pain intensity.

Pain characteristics

NP was assessed using the Douleur Neuropathique en 4 Questions scale[9], 1 day preoperatively and 7 days postoperatively. This 10-item questionnaire (seven symptom descriptions and three clinical examinations) scores one point for each affirmative response and zero points for each negative response. A total score ≥ 4 indicates significant NP components (NP-positive).

Anxiety and depression

Anxiety and depression were assessed using the HADS[10] at preoperative day 1 and at postoperative day 7. The HADS comprises anxiety (A) and depression (D) subscales, each with seven items scored from 0 to 3 points. Total scores range from 0 to 21 points, with a score ≥ 8 indicating potential anxiety/depression.

Postoperative analgesic consumption

The number of effective presses on the intravenous PCA pump and the supplemental analgesic medications administered within 72 hours postoperatively were recorded and converted to milligram equivalents of intravenous morphine.

Early postoperative recovery and quality of recovery

The time to first ambulation, time to first flatus, and length of hospital stay were recorded. Early postoperative recovery quality was assessed using the Quality of Recovery-15 score (QoR-15)[11] (range, 0-150 points; higher scores indicate better recovery quality).

Statistical analysis

Data were analyzed using SPSS 26.0. Count data n (%) were subjected to χ² tests, Shapiro-Wilk tests were used for quantitative data demonstrating a normal distribution, and t-tests were used for between-group comparisons. Stratified regression analysis or generalized estimating equations were utilized, incorporating grouping (observation/control), NP status (positive/negative), and their interaction terms as independent variables, to assess their influence on postoperative day 7 pain intensity. A significant interaction term indicated that NP status moderated the intervention effect. Forest plots were generated to visualize the differences in intervention effects between the NP-positive and NP-negative groups. Differences were considered statistically significant at P < 0.05.

RESULTS

Comparison of pain intensity and pain characteristics

On preoperative day 1, there were no statistically significant differences between the observation and control groups in terms of NRS scores for resting pain, activity-related pain, or NP-positivity rate (P > 0.05). On postoperative day 7, both groups had higher NRS scores for resting and activity-related pain than those on preoperative day 1 (P < 0.05). The observation group had lower NRS scores for resting and activity-related pain and a lower NP-positivity rate than the control group (P < 0.05; Table 2).

Table 2 Comparison of pain intensity and pain characteristics, n (%)/mean ± SD.

Group	n	Resting pain NRS score		NRS score for activity-related pain		Nature of pain (NP-positive)
		Pre-1 day	Post-7 days	Pre-1 day	Post-7 days	Pre-1 day	Post-7 days
Observation	50	2.25 ± 0.91	2.86 ± 0.95a	3.92 ± 1.25	4.72 ± 1.16a	21 (42.00)	18 (36.00)
Control	50	2.14 ± 0.82	4.03 ± 1.38a	3.83 ± 1.19	5.83 ± 1.44a	22 (44.00)	29 (58.00)
t		0.635	4.940	0.369	4.252	0.041	4.878
P value		0.527	< 0.001	0.713	< 0.001	0.840	0.027

^aP < 0.05, compared with pre-treatment levels.

NP: Neuropathic pain; NRS: Numeric Rating Scale; Post: Postoperatively; Pre: Preoperatively.

Comparison of anxiety and depression

On preoperative day 1, there were no statistically significant differences in HADS-A or HADS-D scores between the two groups (P > 0.05). On postoperative day 7, both groups had lower HADS-A and HADS-D scores than those on preoperative day 1 (P < 0.05). The observation group had lower HADS-A and HADS-D scores than the control group (P < 0.05; Table 3).

Table 3 Comparison of anxiety and depression emotions, mean ± SD.

Group	n	HADS-A		HADS-D
		Pre-1 day	Post-7 days	Pre-1 day	Post-7 days
Observation	50	7.24 ± 2.58	5.19 ± 1.87a	6.82 ± 2.36	4.97 ± 1.65a
Control	50	7.63 ± 2.75	8.34 ± 2.40a	7.15 ± 2.52	8.03 ± 2.04a
t		0.731	7.326	0.676	8.248
P value		0.467	< 0.001	0.501	< 0.001

^aP < 0.05, compared with pre-treatment levels.

HADS-A: Hospital Anxiety and Depression Scale-Anxiety; HADS-D: Hospital Anxiety and Depression Scale-Depression; Post: Postoperatively; Pre: Preoperatively.

Comparison of postoperative analgesic consumption, early recovery, and recovery quality

Patients in the observation group had fewer effective presses for intravenous PCA, lower morphine equivalents, earlier time to first ambulation, earlier time to first passage of flatus, and shorter hospital stays than those in the control group (P < 0.05). Their QoR-15 scores were higher than those in the control group (P < 0.05; Table 4).

Table 4 Comparison of pain intensity and pain characteristics, mean ± SD.

Group	n	Effective number of presses for intravenous patient-controlled analgesia (times/72 hours)	Morphine equivalent (mg)	First time getting out of bed (hours)	Initial venting time (hours)	Quality of Recovery-15	Length of hospital stay (days)
Observation	50	15.24 ± 4.36	24.58 ± 6.81	25.54 ± 2.07	68.24 ± 4.06	128.54 ± 12.35	9.26 ± 1.85
Control	50	22.83 ± 5.67	38.23 ± 9.46	32.06 ± 3.11	76.84 ± 5.19	102.75 ± 14.83	10.54 ± 2.30
t		7.502	8.281	12.348	9.227	9.447	3.069
P value		< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	0.003

Moderating effect of NP status on intervention outcomes

Stratified regression analysis showed that the main effects of group assignment and NP status were significant (P < 0.05), as was the interaction term between group assignment and NP status (P < 0.05; Table 5, Figure 1).

Figure 1 Moderating effect of neuropathic pain status on psychological intervention outcomes (forest plot). NP: Neuropathic pain; NRS: Numeric Rating Scale.

Table 5 Analysis of the moderating effect of neuropathic pain status on intervention outcomes.

Predictor variables	β	SD	t	P value
Grouping (observation group/control group)	-1.25	0.18	-6.94	< 0.001
NP status (positive/negative)	0.98	0.21	4.67	< 0.001
Grouping × NP status	-1.05	0.31	-3.39	0.001
Constant term	4.32	0.28	15.43	< 0.001

NP: Neuropathic pain.

DISCUSSION

The primary clinical treatment for GC is surgery; however, perioperative patients frequently encounter pain, anxiety, and depression, which affect postoperative recovery and quality of life. Conventional perioperative pain management centers for pharmacological analgesia often overlook the distinct nature of NP and the regulatory role of psychological factors in pain perception[12,13]. Research indicates[14,15] that NP forms a vicious cycle with negative emotions, such as anxiety and depression, further intensifying the pain experience and delaying postoperative recovery. This study focused on the NP component of perioperative pain in patients with GC and systematically investigated its influence on the efficacy of structured psychological interventions.

Research findings indicated that the Douleur Neuropathique en 4 Questions scale preoperatively identified NP components in 42% of patients in the observation group and 44% in the control group. This result aligns with the 30%-50% NP positivity rates reported by Doan et al[16] and Lakkad et al[17], suggesting that NP components are prevalent in patients with GC and constitute a significant constituent of their complex pain experience. Ni et al[18] reported that NP components are prevalent in patients with GC and constitute an important dimension of their complex pain experiences. This also challenges the conventional clinical categorization of GC-related pain as ‘nociceptive pain’. Regarding pain intensity and characteristics, on postoperative day 7, the observation group exhibited lower NRS scores for resting pain and activity-related pain, a lower NP positivity rate, and reduced HADS-A and HADS-D scores than the control group (P < 0.05). This conclusively demonstrated that psychological intervention effectively reduced perioperative pain intensity and NP positivity rates in these patients with GC. This finding closely aligns with the sensitization-maintenance theory of NP. Inflammatory mediators such as nerve growth factor and tumor necrosis factor-α released from the tumor microenvironment induce peripheral sensitization by activating tropomyosin-regulated kinase A receptors, while surgical trauma further exacerbates central sensitization, forming a pain memory circuit[19,20]. Psychological interventions involving cognitive restructuring and behavioral activation assist patients in developing rational perceptions of pain, surgical procedures, and recovery expectations, which disrupts the vicious cycle of pain-avoidance-functional decline. Mechanistically, affective pain processing in the anterior cingulate cortex and insula may be downgraded, inhibiting glial cell activation and pro-inflammatory factor release, thereby blocking the neuroimmune axis mechanisms of NP[21,22]. Targeted psychological interventions provide patients with channels of emotional expression and psychological support, thereby fostering a sense of care and understanding. This enhances their confidence in managing illness and pain, and teaching them relaxation techniques helps to better regulate physiological and psychological states during painful experiences[23,24]. Such approaches effectively alleviate anxiety and depressive symptoms, while reducing pain amplification caused by tension and apprehension.

The findings further revealed that patients in the observation group exhibited lower rates of effective pressing for intravenous PCA, lower morphine equivalents, earlier times to first ambulation and first flatus, and shorter hospital stays than those in the control group (P < 0.05). However, their QoR-15 scores were higher than those in the control group (P < 0.05). This indicates that psychological intervention not only alleviated the patients’ pain and negative emotions but also promoted the recovery of postoperative physical functions, shortened hospital stay, and enhanced the quality of recovery. Psychological interventions can alleviate patients’ pain and anxiety, placing the body in a relatively relaxed state conducive to the recovery of various bodily functions. Patients in a positive psychological state are more willing to cooperate actively with rehabilitation training and engage in moderate activities[25,26], thereby promoting gastrointestinal motility, accelerating the time to first flatus, and enabling earlier ambulation. Concurrently, psychological interventions diminish reliance on analgesic medications, aligning with contemporary “opioid minimization” pain management strategies. This approach reduces potential adverse drug reactions and offers potential long-term benefits in preventing postoperative chronic pain conditions such as opioid-induced hyperalgesia[27,28], thereby further supporting patients’ physical recovery.

Simultaneously, the stratified regression analysis revealed significant main effects of group assignment and NP status (P < 0.05), along with a significant interaction term between group and NP status (P < 0.05). This finding demonstrated that NP status moderated the efficacy of psychological interventions. The presence or absence of NP is a key determinant in predicting whether patients can derive maximal analgesic and emotional benefits from structured psychological interventions. A core feature of NP is marked central sensitization. In NP-positive patients, spinal dorsal horn neuronal excitability increases, inhibitory control weakens, and glial cell activation typically exceeds that observed in patients with purely nociceptive pain. Episodes often exhibit paroxysmal and provoked characteristics, and patients frequently perceive the pain as unpredictable and uncontrollable[29,30]. Psychological interventions enhance patients’ self-management capabilities and sense of control over pain through psychoeducation, teaching distraction techniques, cognitive disengagement, relaxation, and setting realistic activity goals for behavioral activation. This provides a non-pharmacological, mechanistically complementary analgesic pathway[31,32]. Particularly for NP-positive patients, this approach can reorient the cognitive, emotional, and behavioral response patterns towards NP, disrupting the vicious cycle of pain, and achieving superior analgesic and mood-enhancing effects. NP-negative individuals may exhibit relatively weaker responses to psychological interventions than NP-positive patients. In NP-negative patients, pain perception is predominantly nociceptive in nature, reflecting distinct pain mechanisms from NP-positive counterparts[33,34]. While psychological interventions may alleviate pain and negative emotions to some extent, the absence of prominent central sensitization characteristics in NP-positive patients may limit the mechanisms by which such interventions regulate pain and emotional states[35]. This study had some limitations, including a relatively small sample size, a short observation period, and a single psychological intervention model. Future studies should expand the sample size, prolong the observation period, and investigate diverse psychological intervention approaches to provide a more robust theoretical foundation for precise pain management in clinical practice.

CONCLUSION

In summary, effective identification of the NP component in patients with GC, coupled with perioperative psychological interventions, was shown to significantly reduce pain intensity and NP-positivity rates. This approach improved anxiety and depressive symptoms, decreased postoperative analgesic use, accelerated early postoperative recovery, and enhanced the quality of recovery.