Spinal cord injuries (SCIs) are among the most traumatic events worldwide, which often cause disabilities in patients, affecting and reducing the quality of life [1,2]. These spinal cord injuries may be well treated at the early stages and not severe. However, suppose the injury is severe, in addition to numerous primary problems such as reduced mobility permanent muscle paralysis below the lesion. In that case, these patients may have secondary complications such as pain, pressure ulcers (bedsores), reduced physical activity, reduced social participation, and/or even job loss [3-5].
The most common problems of patients with SCIs are paralysis, atrophy, pain, and spasticity. Still, if no proper treatment is taken for the patient, the patient may suffer from long-term renal and musculoskeletal complications such as pain and osteoporosis [6,7]. Pain is one of the significant problems of patients with SCIs, so a study conducted by Hunt et al. on 37 published articles showed that the chronic pain prevalence was 68%, the prevalence of neuropathic pain was 58%, the prevalence of musculoskeletal pain was 56%. The prevalence of visceral pain was 20% . Neuropathic pain is a recurrent complication of spinal cord injury that may have unknown mechanisms, but major interventions should be performed to reduce it [9,10].
There are various methods to reduce patients' pain with spinal problems, mentioned in previously published articles, pharmacological and non-pharmacological methods [11,12]. There are a variety of drugs available to reduce the pain of patients with spinal problems, including steroidal anti-inflammatory drugs (prednisolone, dexamethasone, methylprednisolone, triamcinolone, and betamethasone) and nonsteroidal anti-inflammatory drugs (diclofenac, brufen, naproxen, and piroxicam) [13,14]. Duloxetine is a series of tricyclic antidepressants that have the potential inhibitory properties of histamine H1 and H2 receptors. It seems that duloxetine can effectively reduce patients' pain by increasing serotonergic and noradrenergic activities [15,16]. Duloxetine is a serotonin and reuptake inhibitor of norepinephrine as a pain inhibitor used in lower back pain, fibromyalgia, orthopedic surgery, knee pain, and for the treatment of diseases with psychiatric disorders [17,19].
Due to the importance of reducing the pain of patients and the role of physicians in identifying the types of drugs needed to reduce pain, it is necessary to conduct further studies. Also, since there was no systematic review in this field. For this reason, the present study was conducted aimed to evaluate the effect of duloxetine on the pain status of patients with SCIs by systematic review.
The present systematic review was conducted observing principles of publication ethics and guidelines of systematic reviews and meta-analyzes (PARISMA)  aimed to investigate the effect of duloxetine on the pain status of patients with SCIs during 2010-2021.
Search strategy and selection of studies
Two researchers who were proficient in SCIs (Assistant Professor of Neurosurgery) performed the search and reviewed review articles. The search was performed in all domestic databases in Iran (SID, Iran Doc, RICST), Google Chrome search engine, and the following international databases. Such as the Web of Science, Science Direct, Scopus, Embase, PubMed/Medline, EBSCO, CINAHL, Cochrane Library, EMBASE.
The "All Fields" option was used for the search, and the searched keywords are described in Table 1. In Persian language databases inside Iran, Persian equations of English keywords were used, and a search was performed.
Inclusion and exclusion criteria
Inclusion criteria included articles published with the spinal group in which the effect of duloxetine on pain status was investigated. Also, the scope of the article search was during 2010-2021 in Persian and English. Articles on other groups of patients with incomplete data, qualitative studies, review studies, case report studies, case series studies, and articles on the non-human group were excluded from the study.
A checklist including author’s name, publication date, Outcomes, Control, Intervention, Population, and Study design was used for data collection.
Using Excel 2007 Software, the collected data were classified, and the final report is given in Table 2.
Search results and features
According to Figure 1, 202 articles were included in the study in the first stage. 154 articles were deleted due to the irrelevance of the title and method of the article. Also, 34 articles were done due to duplication of articles, and 8 articles were done due to non-human studies. Finally, 6 articles entered the systematic review stage.
Demographic characteristics articles reviewed
Out of 64 reviewed articles, 6 articles entered the systematic review (Altiparmak et al. ., Prabhala et al. (2019) , Tsuji et al. , Samadi et al. (2021) , Hyer et al. (2015) , and Vranken et al. (2011) ). Except for the article published by Tsuji et al. , which was a retrospective observational type, the rest of the published articles were RCT type. In all 6 articles, the total sample size was 298 patients, and most of the patients were female. Regarding the effect of duloxetine on the pain status of patients with spinal cord problems in all 6 articles, the results showed that duloxetine can reduce patients' pain. The flowchart of articles entered the systematic review is shown in Figure 1.
Role of doxepin in reducing pain
In all reviewed articles, it was shown that doxepin effectively reduces pain and can reduce pain. While in the placebo group, patients' pain did not decrease.
The present study was conducted aimed to investigate the effect of duloxetine on pain status in patients with spinal cord injuries. According to the study results, duloxetine can effectively reduce the pain of patients with spinal cord injuries. This study was conducted for the first time in the world on a group of patients with spinal cord injuries, so the results will be compared with other studies in which duloxetine has been used on the pain of other patients. Patients with spinal cord injuries experience a lot of pain, and finding ways to reduce pain is one of the objectives of experts in this field . Regarding the presence of pain in patients with spinal cord injuries, the results of Hatefi et al.'s meta-analysis showed that pain in patients with SCI in Iran was 65.9%, indicating a high prevalence of pain in these patients .
According to the study results, it reduces patients' pain with spinal cord injuries. A study by Hirase et al. on 5 articles prescribing duloxetine to 832 patients with CLBP showed that in all studies, patients' pain was reduced after taking duloxetine and a significant difference between was the pain of the patients who received duloxetine and the placebo group . Another meta-analysis investigating the effect of duloxetine on pain was published in a study by CHEN et al. on 2059 patients showed that their pain was reduced after taking this drug . Duloxetine is also prescribed to reduce pain in patients with neuropathy and fibromyalgia. According to a study by Sultan et al. duloxetine has been prescribed as a placebo for 1510 patients for 12-13 weeks. According to the results, prescribing this drug has reduced patients with painful diabetic neuropathy , which is consistent with the study results.
One of the limitations of this study is not conducting a meta-analysis study and reporting the data in a systematic review. It is suggested to conduct a meta-analysis study for another intervention in this field and obtain more results. Other limitation of this study is the heterogeneity of the articles reviewed and the questionnaire used. For this reason, the study results were reported in a systematic review. One of the strengths of this study is the novelty of the study, which no study has been conducted in this field so far, and therefore can be helpful as a suitable clinical finding.
Due to the effect of duloxetine on reducing pain in patients with SCIs, it is suggested that duloxetine can reduce pain in patients.
The authors are grateful to Ilam University of Medical sciences, Ilam, Iran.
Masoud Hatefi: https://orcid.org/0000-0002-1529-2419
Khalil Komlakh: https://orcid.org/0000-0002-8291-5540
RCT: double-blind randomized controlled trial
IG: Intervention group
CG: Control group
CP: Chronic Pain
PCN: Postsurgical chronic numbness
SCS: Spinal cord stimulation
PSF: Posterior spinal fixation
CLBT: chronic low back pain
R: systematic review and meta-analysis
SCIs: Spinal cord injuries
RICST: Regional Information Center for Science and Technology
SID: Scientific Information Database
Iran Doc: Iranian Research Institute for Information Science and Technology
How to cite this article: Masoud Hatefi, Khalil KomLakh*. Investigation of the effect of Duloxetine on pain status of patients with spinal cord injuries: A systematic review of drug therapy. Eurasian Chemical Communications, 2022, 4(3), 256-262. Link: http://www.echemcom.com/article_144433.html
Copyright © 2022 by SPC (Sami Publishing Company) + is an open access article distributed under the Creative Commons Attribution License(CC BY) license (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.