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The Effect of Preoperative Oral Melatonin on Postoperative Pain after Lumbar Disc Surgery: A Double-Blinded Randomized Clinical Trial

December 2022

Baradari AG, Habibi MR, Aarabi M, et al. The Effect of Preoperative Oral Melatonin on Postoperative Pain after Lumbar Disc Surgery: A Double-Blinded Randomized Clinical Trial. Ethiop J Health Sci. 2022;32(6):1193-1202. doi:10.4314/ejhs.v32i6.17


Overview

This double-blind, randomized, placebo-controlled trial that included 80 individuals was conducted to investigate the effectiveness of oral melatonin to aid in the reduction of postoperative pain after a lumbar laminectomy/discectomy.  Four groups received either a placebo or a dose of 3, 5, or 10 mg of melatonin 1 hour before surgery.  Pain was measured 6, 12, and 24 hours post-surgery.  The melatonin-treated group reported significantly less pain (P<0.001) than the placebo group, though no statistical significance was noted between the 3 treated melatonin groups. 


Our comments/takeaway from the article

Using oral melatonin was shown to be significant in reducing post-operative pain following a lumbar laminectomy/discectomy compared to placebo. Interestingly, while each of the three melatonin-treated groups reported less pain than the placebo group, there was not a significant difference in the pain reported between the melatonin-treated groups. Thus, the biggest takeaway from this article is that the model of using the lowest, most effective dose of melatonin for this clinical purpose may be best. 


Article summary

Lumbar discectomy is a common surgery performed to address disc herniation. Reducing post-operative pain can decrease complications and improve outcomes such as decreasing immobility time. Since anesthesia can reduce plasma levels of melatonin, the authors suggest that supplemental melatonin use is recommended prior to surgery. 


Melatonin is a known anti-inflammatory agent and antioxidant, but it is also reported to have analgesic effects, though the exact mechanism is not fully understood. It is suggested that the stimulation of endorphins as well as melatonin’s effect on opioid, benzodiazepine, and serotonergic receptors as well as GABA and nitric oxide arginine pathways may contribute. Based on other studies suggesting melatonin’s effectiveness for reducing pain following cesarean section, hysterectomy, and prostatectomy, the author’s hypothesized that treatment of melatonin would reduce post-operative pain for a discectomy. 


This parallel, double-blind randomized controlled clinical trial, included 80 individuals undergoing open lumbar laminectomy and discectomy. Four (4) groups were randomized to be given placebo or 3 mg, 5 mg, or 10 mg of oral melatonin 1 hour prior to the scheduled surgery.  All patients were given the same anesthesia and all surgeries were performed by the same surgeon, utilizing the same surgical approach.  


Pain was monitored at 6, 12, and 24 hours following the surgery using the validated Visual Analog Scale (VAS), with morphine given to those who rated their pain above a 3. All patients were given paracetamol (1 gram) every 8 hours to aid in pain control. 


Inclusion criteria:

  • 35-70 years old

  • Diagnostic tests to determine the need for discectomy included a physical exam, CT, and MRI

  • Elective surgery status 


Exclusion criteria:

  • Emergency surgery status

  • More than two lumbar discs required surgery

  • Opioid drug use up to 12 hours before surgery

  • Alcohol/drug abuse history

  • Previous spinal surgery

  • History of unusual complications during surgery 


The primary outcome of this study was the severity of postoperative pain. The secondary outcomes included opioid use, nausea, vomiting, pruritis, and patient satisfaction. 


The results of the study included:

  • Significantly less pain was reported in all melatonin-treated groups compared to placebo (p<0.001)

  • No significant difference in pain levels was reported between the 3 melatonin treated groups (p>0.05)

  • The request for opioid medication was not significantly different between the groups.

  • Post hoc testing indicated a significant decrease in the request for opioid medication in the 5 mg treated group compared to the placebo group (p<0.04), though all melatonin groups received less opioid medication than the placebo, though not to statistical significance.

  • There was no significant difference in the severity of nausea, pruritus, or vomiting between the groups (secondary outcomes)

  • No side effects of using melatonin were observed. 


The author’s note, “...no decisive conclusion can be drawn regarding the optimal dose of melatonin in terms of its analgesic effects.” Based on current literature, they have suggested 5-20 mg of melatonin for this clinical use, though further studies are needed to define this recommendation. 


Author’s limitations include:

  • Selective bias is possible

  • VAS (pain score) is a subjective measure

  • Many factors influence one’s pain level/perception 


Other limitations noted in our review:

  • One time dosing of melatonin was used prior to surgery only

  • Unknown medical history of individuals

  • Inflammatory markers were not measured, which may provide insight into perceived pain levels

  • A wide range in the age group (35-70 yo) 



Article review completed by Kim Ross,

DCNContent reviewed by Deanna Minich,

PhDDecember 18, 2022

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