The efficacy of gabapentin supplementation for pain control after lumbar laminectomy and discectomy: A meta-analysis study

Abstract

Background:

Gabapentin supplementation may have some potential in pain control after lumbar laminectomy and discectomy, and this meta-analysis aims to explore the impact of gabapentin supplementation on postoperative pain management for lumbar laminectomy and discectomy.

Methods:

PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials assessing the effect of gabapentin supplementation on the pain control of lumbar laminectomy and discectomy.

Results:

Five randomized controlled trials were finally included in the meta-analysis. Overall, compared with control intervention for lumbar laminectomy and discectomy, gabapentin supplementation was associated with significantly lower pain scores at 2 hours (MD = −2.75; 95% CI = −3.09 to −2.41; P < .00001), pain scores at 4 hours (MD = −2.28; 95% CI = −3.36 to −1.20; P < .0001), pain scores at 24 hours (MD = −0.70; 95% CI = −0.86 to −0.55; P < .00001) and anxiety score compared to control intervention (MD = −1.32; 95% CI = −1.53 to −1.11; P < .00001), but showed no obvious impact on pain scores at 12 hours (MD = −0.58; 95% CI = −1.39 to 0.22; P = .16). In addition, gabapentin supplementation could significantly decrease the incidence of vomiting in relative to control intervention (OR = 0.31; 95% CI = 0.12–0.81; P = .02), but they had similar incidence of nausea (OR = 0.51; 95% CI = 0.15–1.73; P = .28).

Conclusions:

Gabapentin supplementation benefits to pain control after lumbar laminectomy and discectomy.

1. Introduction

Lumbar laminectomy and discectomy commonly cause obviously postoperative pain which is caused by peripheral mechano-receptor stimulation.^[1–5] Inflammatory, neurogenic and visceral mechanisms participate the formation of acute pain symptoms.^[6,7] Postoperative pain seriously delays the discharge of patients, prolongs the recovery period and affects the patients’ quality of life.^[8–11] It is crucial to take necessary measures to reduce the patient’s pain. Current analgesics mainly include opioids and nonsteroidal anti-inflammatory drugs, but they are limited by insufficient analgesic efficacy, respiratory depression, and peptic ulcer.^[10,12–14]

As one new anticonvulsant, gabapentin is similar to amino acid inhibitory amino acid with aminobutyric acid.^[15,16] Gabapentin displays an important role in analgesic, anticonvulsant, and anxiolytic effects with limited adverse effects.^[17] Gabapentin also demonstrated important potential in alleviating neuropathic pain, chronic pain and postoperative pain.^[18–20] Several RCTs reported that gabapentin may have the capability to improve pain control after lumbar laminectomy and discectomy, but the results were not well established.^[17,21,22] Therefore, this meta-analysis aimed to evaluate the effectiveness of gabapentin versus placebo on postoperative pain intensity of lumbar laminectomy and discectomy.

2. Materials and methods

2.1. Study selection and data collection

This meta-analysis of previously studies did not need ethical approval and patient consent and was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISM) statement and Cochrane Handbook for Systematic Reviews of Interventions.^[23,24] This protocol was registered in PROSPERO (CRD42023477073).

We have searched PubMed, EMbase, Web of science, EBSCO, and the Cochrane library up to December 2022, using the search terms “gabapentin” and “laminectomy” or “discectomy.” The inclusion criteria were as follows: study design was RCT; participants underwent lumbar laminectomy and/or discectomy; (3) intervention treatments were gabapentin supplementation versus placebo.

2.2. Assessment for risk of bias

Two reviewers independently carried out quality assessment of included studies according to the Cochrane Handbook for Systematic Reviews of Interventions. We used the Risk of Bias 2.0 (RoB 2.0) tool to evaluate the risk of bias of RCTs.^[25] Any discrepancy was solved by consensus.

2.3. Outcome measures

The following information was extracted: first author, publication year, sample size, age, female, duration of surgery, and methods of 2 groups. The primary outcomes were pain scores at 2 hours and pain scores at 4 hours. Secondary outcomes included pain scores at 12 hours, pain scores at 24 hours, anxiety score, vomiting and nausea.

2.4. Statistical analysis

A team consisting of 3 authors did the statistical analyses. Mean difference (MD) with 95% confidence interval (CI) was used to assess continuous outcomes. I² statistic was used to assess the heterogeneity, and significant heterogeneity was observed when I² > 50%.^[26] The random-effect model was used for significant heterogeneity, and otherwise fixed-effect model was applied. We conducted the sensitivity analysis through detecting the influence of a single study on the overall estimate via omitting one study in turn or using the subgroup analysis. P ≤ .05 indicated statistical significance and Review Manager Version 5.3 was used in all statistical analyses.

2.5. Quality of evidence

The quality of evidence for each outcome was evaluated based on the methodological quality and the confidence in the results, and it was assessed by GRADE recommendations as high quality, moderate quality, low quality, or very low quality.^[27]

3. Results

3.1. Literature search, study characteristics, and quality assessment

The flow chart for the selection process and detailed identification was presented in Figure 1. Two hundred thirty two publications were identified through the initial search of databases. Ultimately, 5 RCTs were included in the meta-analysis.^{[17,21,22,28,29]}

Figure 1.

Flow diagram of study searching and selection process.

The baseline characteristics of 5 eligible RCTs in the meta-analysis were summarized in Table 1. The 5 studies were published between 2005 and 2018, and total sample size was 322. There were similar characteristics between gabapentin group and control group at baseline. Gabapentin was used before the surgery, and its doses ranged from 300 to 900 mg.

Table 1.

Characteristics of included studies.

	Author	Gabapentin group					Control group					Jada scores
		Number	Age (yrs)	Female (n)	Duration of surgery (min)	Methods	Number	Age (yrs)	Female (n)	Duration of surgery (min)	Methods
1	Javaherforooshzadeh et al[17]	30	45 ± 6.1	16	80 ± 5.2 min	600 mg gabapentin before induction of anesthesia	30	48 ± 5.6	15	75 ± 5.1 min	Placebo	4
2	Vasigh et al[21]	38	49.5 ± 5.9	7	2.27 ± 0.28 h	600 mg gabapentin before surgery	38	50.2 ± 7.2	10	2.11 ± 0.23 h	Placebo	5
3	Vahedi et al[22]	36	44.5 ± 10.37	–	–	300 mg gabapentin before surgery	40	44.4 ± 10.56	–	–	600 mg gabapentin before surgery	4
4	Khan et al[28]	25	41.9 ± 10.7	10	155.5 ± 28	900 mg gabapentin before surgery	25	41.0 ± 10.5	10	154.6 ± 17.8	Placebo	3
5	Radhakrishnan et al[29]	30	39.63 ± 10.87	–	163.4 ± 31.99	400 mg gabapentin before surgery	30	41.67 ± 12.06	–	168.67 ± 12.86	Placebo	4

Among the 5 RCTs, 2 studies reported pain scores at 2 hours and pain scores at 4 hours,^[21,28] 3 studies reported pain scores at 12 hours,^[21,22,28] 2 studies reported pain scores at 24 hours,^[21,22] 2 studies reported anxiety score,^[17,21] and 2 studies reported vomiting and nausea.^[21,28] Jadad scores of the 5 included studies ranged from 3 to 5, and all studies were considered to be high-quality ones according to quality assessment.

3.2. Assessment of risk of bias

All 5 RCTs were assessed by RoB 2.0. Three of them were judged with some concerns in the risk of bias.^[17,28,29] Three RCTs did not clearly describe the randomization process and/or intended interventions (Table 2). The quality of evidence for each outcome by GRADE recommendations was presented (Fig. 2).

Table 2.

Risk of bias assessment (RoB 2.0).

No.	Author and year	Bias arising from the randomization process	Bias due to deviations from intended interventions	Bias due to missing outcome data	Bias in measurement of the outcome	Bias in selection of the reported result	Overall assessment
1	Javaherforooshzadeh et al[17]	Low risk	Some concerns	Low risk	Low risk	Low risk	Some concerns
2	Vasigh et al[21]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
3	Vahedi et al [22]	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
4	Khan et al[28]	Some concerns	Some concerns	Low risk	Low risk	Low risk	Some concerns
5	Radhakrishnan et al[29]	Some concerns	Low risk	Low risk	Low risk	Low risk	Some concerns

Figure 2.

The quality of evidence for each outcome by GRADE recommendations.

3.3. Primary outcomes: pain scores at 2 hours and pain scores at 4 hours

Compared to control group for lumbar laminectomy and discectomy, gabapentin supplementation was associated with significantly reduced pain scores at 2 hours (high quality, MD = −2.75; 95% CI = −3.09 to −2.41; P < .00001) with no heterogeneity among the studies (I² = 0%, heterogeneity P = .62, Fig. 3) and pain scores at 4 hours (low quality, MD = −2.28; 95% CI = −3.36 to −1.20; P < .0001) with significant heterogeneity among the studies (I² = 88%, heterogeneity P = .004, Fig. 4).

Figure 3.

Forest plot for the meta-analysis of pain scores at 2 h.

Figure 4.

Forest plot for the meta-analysis of pain scores at 4 h.

3.4. Sensitivity analysis

Significant heterogeneity was observed for pain scores at 4 hours. We did not perform the sensitivity analysis by omitting one study in each turn because there were only 2 RCTs.

3.5. Secondary outcomes

Compared with control intervention for lumbar laminectomy and discectomy, gabapentin supplementation showed no obvious impact on pain scores at 12 hours (very low quality, MD = −0.58; 95% CI = −1.39 to 0.22; P = .16; Fig. 5), but resulted in substantially reduced pain scores at 24 hours (high quality, MD = −0.70; 95% CI = −0.86 to −0.55; P < .00001; Fig. 6). In addition, gabapentin supplementation could significantly decrease anxiety score compared to control intervention (moderate quality, MD = −1.32; 95% CI = −1.53 to −1.11; P < .00001; Fig. 7). In terms of safety, vomiting and nausea were thought to be the most common adverse events among the included RCTs.^[21,28] In comparison with control intervention, gabapentin supplementation could significantly decrease the incidence of vomiting (very low quality, OR = 0.31; 95% CI = 0.12–0.81; P = .02; Fig. 8), but showed no influence on nausea (very low quality, OR = 0.51; 95% CI = 0.15–1.73; P = .28; Fig. 9).

Figure 5.

Forest plot for the meta-analysis of pain scores at 12 h.

Figure 6.

Forest plot for the meta-analysis of pain scores at 24 h.

Figure 7.

Forest plot for the meta-analysis of anxiety score.

Figure 8.

Forest plot for the meta-analysis of vomiting.

Figure 9.

Forest plot for the meta-analysis of nausea.

4. Discussion

In this meta-analysis, we included 5 RCTs and 322 patients undergoing lumbar laminectomy and discectomy. The results confirmed that gabapentin supplementation could significantly reduce pain scores at 2 hours, pain scores at 4 hours, pain scores at 24 hours and anxiety score compared to control intervention, but showed no obvious impact on pain scores at 12 hours.

Our results confirmed the efficacy of gabapentin supplementation to alleviate pain and anxiety after lumbar laminectomy and discectomy. However, there was significant heterogeneity for pain scores at 4 hours. Several factors may account for the heterogeneity. First, patients underwent different surgical procedures including lumbar laminectomy and/or discectomy. Second, the doses of gabapentin ranged from 300 to 900 mg, which caused some bias. Third, although gabapentin was used before the surgery, the detailed time for gabapentin use was not completely same.

In terms of safety, gabapentin supplementation resulted in decreased incidence of vomiting compared to control intervention. With regard to the mechanisms of gabapentin supplementation for analgesic effect, gabapentin is able to reduce the voltage-dependent membrane calcium flow to the posterior nerve endings of the ganglia and the neurotransmitter release, which reduces the sensitivity of sensory nerves dependent on calcium.^[20,30,31] In addition, gabapentin analgesic function is improved by the regulation of glutamate receptors (n-methyl-d-aspartic acid and α-amino-3-methyl-4-isoxazole-propionate/caynate).^[32,33]

We should also consider several limitations. First, our analysis was based on only 5 RCTs and more studies with large patient samples should be conducted to confirm these findings. Second, the detailed doses and methods of gabapentin were different in the included studies, and its ideal dose remained elusive. Third, different surgical procedures including lumbar laminectomy and discectomy were involved, which may affect the pooling results.

5. Conclusion

Gabapentin supplementation benefited to reduce the pain and anxiety after lumbar laminectomy and discectomy.

Author contributions

Conceptualization: Ruhui Li, Wenbin Lei.

Formal analysis: Ruhui Li.

Funding acquisition: Ruhui Li, Xiongbin Yao.

Resources: Ruhui Li, Wenbin Lei.

Software: Ruhui Li, Wenbin Lei.

Supervision: Wenbin Lei.

Writing – original draft: Xiongbin Yao.

Writing – review & editing: Xiongbin Yao.