Abstract

Background: Given the established effectiveness of gabapentin and NSAIDs in reducing postoperative pain and the paucity of comparative studies of gabapentin and NSAIDs for postoperative pain management, our current study was designed to assess and compare the effectiveness of celecoxib and gabapentin in preventing post-cesarean section pain.

Methods: This randomized clinical trial was conducted on pregnant women who underwent elective caesarean sections with spinal anesthesia who were referred to Mousavi Hospital, Iran, in 2022. Patients meeting inclusion criteria were grouped via balanced block randomization into three groups. Group 1 received 600 mg of gabapentin and group 2 received 200 mg of celecoxib 1 hour before the surgery, while group 3 did not receive any pain-relief medication before the surgery. Patients’ pain levels were recorded using the visual analog scale (VAS) in the recovery room, as well as at 1, 6, 12, and 24 hours after surgery. Comparisons between groups were made using one-way ANOVA and chi-squared tests.

Results: The mean age of participating mothers was 27.4 ± 4.69 years. There were no statistically significant differences in the mean nausea levels or the request for additional medication among the groups at any time points (0, 1, 6, 12, and 24 hours after the intervention) in mothers following cesarean section surgery (p > 0.05). At all time points, the mean VAS score in the gabapentin group was lower than in the celecoxib and control groups (p < 0.05).

Conclusion: Our study suggests that preoperative administration of 600 mg of gabapentin can effectively reduce postoperative pain in women undergoing elective cesarean section surgery. No significant differences in side effects were observed among groups. This research highlights the potential of gabapentin as a valuable component of pain management strategies for cesarean section patients.

Introduction

Pain following a cesarean section is a substantial source of concern for numerous women. During this period, the mother not only has to endure the pain resulting from the cesarean section but also must be capable of caring for the newborn, who requires special attention1. Furthermore, achieving effective pain relief following a cesarean section is of paramount importance given the heightened risk of thromboembolic conditions that can exacerbate due to the immobility resulting from postpartum pain2. The following consequences of these complications include various economic and medical concerns, such as prolonged hospitalization, the need for re-hospitalization, increased patient recovery costs, and ultimately patient dissatisfaction with hospital care3.

Traditional approaches to managing acute postoperative pain primarily involve the administration of oral or injectable analgesic medications on an as-needed basis. Narcotic medications, especially in injectable form, are commonly utilized to alleviate acute pain. However, postoperative pain is a complex phenomenon that cannot be effectively controlled by single-agent narcotic therapy alone. Furthermore, the use of narcotics is associated with dose-dependent side effects, including respiratory depression, nausea, vomiting, urinary retention, itching, sedation, and postoperative ileus. Therefore, it appears reasonable and rational to administer substances that can enhance the analgesic effects of narcotics, ultimately leading to improved pain relief with reduced opioid consumption4, 5.

Chronic postoperative pain often has a neuropathic component. Neuropathic pain can even be observed in the early stages after surgery. For this reason, drugs traditionally used to treat chronic neuropathic pain are increasingly being used as adjunctive therapy for postoperative pain6. These drugs include antidepressants like amitriptyline, anticonvulsants like gabapentinoids, N-methyl-D-aspartate (NMDA) receptor antagonists like ketamine and magnesium, membrane stabilizers like lidocaine, and alpha-2 agonists like clonidine. Recent studies have demonstrated that drugs like gabapentin and pregabalin can not only alleviate the intensity of acute postoperative pain and reduce the need for opioids but also can contribute to the prevention of chronic postoperative pain7.

The most recognized mechanism for the analgesic effects of gabapentinoids is their binding to the α2δ-1 subunit of voltage-gated calcium channels at presynaptic synapses and the modulation of neurotransmitter release, particularly of glutamate, which reduces neuronal excitability and central sensitization, leading to hypoalgesia and allodynia8. Recent studies have demonstrated that these drugs disrupt the transfer of α2δ-1 subunits to the terminals of dorsal root ganglion (DRG) neurons, reducing calcium influx into the cell. Nonetheless, alternative mechanisms have been suggested for the action of these drugs, which involve the activation of inhibitory pathways within the noradrenergic pain system in the spinal cord and brain, heightened activity of voltage-gated potassium channels, and impacts on NMDA receptors. However, the precise degree to which these mechanisms play a role in the analgesic effects of these drugs remains incompletely understood9, 10. Another group of drugs used to reduce postoperative pain and mitigate the side effects associated with opioid use includes NSAIDs. This drug class inhibits the enzyme cyclooxygenase, which prevents the production of prostaglandins that cause inflammation, fever, and pain11.

Considering the results of this previous research on the beneficial effects of gabapentin and NSAIDs in managing post-cesarean section pain, as well as the limited number of studies in this area and the significant side effects, particularly the risk of respiratory depression, associated with conventional analgesic drugs frequently used during cesarean sections, it becomes imperative to explore alternative and more suitable options for pain relief in these patients. Given the established effectiveness of gabapentin and NSAIDs in reducing postoperative pain and the paucity of comparative studies of gabapentin and NSAIDs for postoperative pain management, our current study was designed to assess and compare the effectiveness of celecoxib and gabapentin in preventing post-cesarean section pain.

Methods

The present study was a randomized controlled clinical trial conducted in 2022 at Ayatollah Mousavi Hospital in Zanjan, Iran, with the aim of comparing the effectiveness of celecoxib and gabapentin in reducing post-cesarean section pain in pregnant women.

The inclusion criteria for study participation were as follows: patient’s voluntary willingness to participate, eligibility for non-emergency cesarean section surgery, absence of allergies to gabapentin and NSAIDs, age between 20 and 45 years, lack of contraindications for spinal anesthesia (e.g., patient dissatisfaction and coagulation disorders), lack of infection at the injection site, lack of history of chronic pain or neurological or psychiatric disorders, and lack of use of any pain-relief medication in the 24 hours prior to the study. Exclusion criteria included patient withdrawal from the study at any point, cesarean section duration exceeding 2 hours, an increase in incision length for any reason, occurrence of unusual complications during surgery, conversion from spinal anesthesia to general anesthesia for any reason, and receiving pain-relief medication during the surgery.

The study protocol received approval from the ethics committee of Zanjan University of Medical Sciences under the code IR.ZUMS.REC.1401.051. Additionally, the study was registered in the Iranian Registry of Clinical Trials (IRCT) with the code IRCT20220517054889N1. Patients meeting the inclusion criteria were selected as a convenience sample. They were first classified into three groups using balanced block randomization for intervention assignment:

Group 1 received 600 mg of gabapentin 1 hour before the surgery.Group 2 received 200 mg of celecoxib 1 hour before the surgery.Group 3, the control group, did not receive any pain-relief medication prior to the surgery.

Prior to the commencement of surgery, patients received an explanation of the visual analog scale (VAS) for pain assessment. On this scale, 0 signifies the absence of pain, while 10 denotes the most severe pain. Patients’ pain levels were documented using this scale in the recovery room, as well as at 1, 6, 12, and 24 hours post-surgery. Any potential side effects stemming from the medications, such as seizures, reduced level of consciousness, nausea, and vomiting, were likewise recorded during the 24 hours following the surgical procedure.

At any time following the cesarean section when a patient reported pain on the VAS greater than or equal to 4, an additional dose of diclofenac suppository (100 mg) was administered. The cumulative quantity of supplementary pain-relief medication administered to patients within a 24-hour period was calculated and documented.

Data were collected using a researcher-designed checklist that included demographic and clinical variables such as age, history of previous pregnancies, underlying diseases, and pregnancy-related illnesses.

To compare the means of each of the examined variables before and after the intervention among the three groups, ANOVA was employed. When variables failed to meet the assumption of normality, Kruskal–Wallis nonparametric tests were used instead. To compare qualitative variables among the three groups, chi-square tests were employed. In the final analysis, a repeated measures ANOVA was used to compare the mean pain intensity at different time points among the three groups. The data were analyzed using SPSS software, version 24, with a significance level set at p

Results

Of a total of 102 candidates for participation in the research, 8 individuals did not meet the entry criteria, and 4 participants declined to participate in the study. Ultimately, analysis was conducted with data from 90 individuals. Figure 1 illustrates a flowchart describing the clinical trial.

× Figure 1 . CONSORT flowchart of the study . Figure 1 . CONSORT flowchart of the study .

Table 1.

Distribution of individual characteristics and clinical information of the mothers and Neonatal in interventions and control groups

Variable Gabapentin group (n = 30) Celecoxib group (n = 30) Control group (n = 30) P value* Mother’s weight (kg) (Mean ± SD) 83.8 ± 8.64 83.11 ± 11.3 83.99 ± 9.23 0.963 a Neonatal ‘s weight (kg) (Mean ± SD) 3.37 ± 0.71 3.46 ± 0.63 3.61 ± 0.56 0.325 a Age (years) (Mean ± SD) 28.1 ± 4.42 27.77 ± 4.59 27.87 ± 5.2 0.962 a Apgar (Mean ± SD) 8.0 ± 0.69 7.93 ± 0.69 7.90 ± 0.66 0.848 a

Table 2.

Comparison of sleepiness in 3 study groups at time point zero (recovery) after cesarean surgery

Control group (n = 30) Celecoxib group (n = 30) Gabapentin group (n = 30) Total p-value Sleepiness n 1 1 0 2 0.600 Frequency 3.3% 3.3% 0% 2.2%

Table 3.

Comparison of nausea in 3 study groups at time points 0 (recovery), 1, 6, 12, and 24 hours after cesarean surgery

Time Gabapentin group (n = 30) Gabapentin group (n = 30) Control group (n = 30) Total p-value Recovery, n (%) 15 (50%) 17 (56.7%) 16 (53.3%) 48 (53.3%) 0.875 1 hour later, n (%) 22 (73.3%) 17 (56.7%) 19 (63.3%) 58 (64.4%)