Alternative Options for Complex, Recurrent Pain States Using Cannabinoids, Psilocybin, and Ketamine: A Narrative Review of Clinical Evidence
, Juliana M. Fort 1, Christina Singh 1, Sarah E. Wagner 2, Jessica R. Rodriguez 2, Catherine A. Johnson 2, Elyse M. Cornett 3, Kevin S. Murnane 1,4,5, Adam M. Kaye 6 and Alan D. Kaye 3Round 1
Reviewer 1 Report
This review has intended to provide information on the use of non-opioids for pain management. It is advisable to consider the following parts in the composition of the content.
1. It is suggested that the subject be narrated in four large known categories. (eg. 1. Nonsteroidal anti-inflammatory drugs; 2. Acetaminophen; 3. COX-2 inhibitors; 4. Antidepressants and anti-seizure medications; 5. (and if any)).
2. Cancer pain and CRPS are the most important diseases related to complex pain, but it is wondering as to why they were not mainly handled.
3. A separate table should also be provided for the clinical cases in the use of cannabinoids.
4. It is also suggested to describe certain cases of complex pain management related to central and peripheral nerve damage separately.
Author Response
This review has intended to provide information on the use of non-opioids for pain management. It is advisable to consider the following parts in the composition of the content.
1. It is suggested that the subject be narrated in four large known categories. (eg. 1. Nonsteroidal anti-inflammatory drugs; 2. Acetaminophen; 3. COX-2 inhibitors; 4. Antidepressants and anti-seizure medications; 5. (and if any)).
Answer: We feel that presenting this in a stepwise fashion as that is what is recommended to do clinically. We feel it better to present this like the guidelines in the ladder treatment model. If we break it into categories, we may need to lengthen these sections and that would not add to this manuscript.
2. Cancer pain and CRPS are the most important diseases related to complex pain, but it is wondering as to why they were not mainly handled.
Answer: The reason that it wasn’t handled in this paper is we were trying to limit what was presented to what the studies also aligned to.
3. A separate table should also be provided for the clinical cases in the use of cannabinoids.
Answer: This has been added
4. It is also suggested to describe certain cases of complex pain management related to central and peripheral nerve damage separately.
Answer: We’re not sure if that would add to the paper as we described briefly treatments but wanted to focus more solely on the alternative treatments.
Reviewer 2 Report
This is an overall nice work. I would encourage the authors to consider a more specific title. ''Alternative Options for Complex, Recurrent Pain States'' is a quite general description. Moreover, orexin should not be discussed more extensicely than other widely used treatments. The ''Side effects of opioids'' should be placed proximally to their description in ''The Ladder of Treatment for Chronic Pain''. The section of ''Multimodal Treatments'' appears to be rather unstrauctured. There appears to be no connection between several concepts: e.g., ''Chronic low back pain is another condition that may benefit from combination drug therapy due to the presence of both neuropathic and nociceptive pain mechanisms. Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbance, and memory and mood issues.'' In general, the first part of the review is rather unstructured and deficient. I understand that the purpose of this study is to focus on alternative options; however, since it was decided to describe other treatments as well, please pay improve its structure and content.
Author Response
This is an overall nice work. I would encourage the authors to consider a more specific title. ''Alternative Options for Complex, Recurrent Pain States'' is a quite general description. Moreover, orexin should not be discussed more extensicely than other widely used treatments. The ''Side effects of opioids'' should be placed proximally to their description in ''The Ladder of Treatment for Chronic Pain''. The section of ''Multimodal Treatments'' appears to be rather unstrauctured. There appears to be no connection between several concepts: e.g., ''Chronic low back pain is another condition that may benefit from combination drug therapy due to the presence of both neuropathic and nociceptive pain mechanisms. Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbance, and memory and mood issues.'' In general, the first part of the review is rather unstructured and deficient. I understand that the purpose of this study is to focus on alternative options; however, since it was decided to describe other treatments as well, please pay improve its structure and content.
Answer: Thank you for your comments. We hope the revisions we made here make this manuscript better.
Reviewer 3 Report
Thank you for allowing me to review the article "Alternative Options for Complex, Recurrent Pain States: A Narrative Review of Clinical Evidence ".
The study evaluated chronic pain management with alternative
and combinations of medications in the treatment of chronic pain. The authors conducted an extensive and careful review of the literature following standard bibliography evaluation guidelines. The conclusion of the study is that chronic pain management is a complex problem across healthcare and is a significant factor in the quality of life for individuals affected
While strong methodologically, the manuscript does not deliver a clear message in key sections because of grammar weaknesses (e.g., awkward sentences). The first paragraph of the Discussion is particularly problematic and less impactful than the last two sentences of the Abstract. There are also typo errors.
It is an original work, very ambitious and of great importance in public health.
The title should be adjusted to the content of the work.
I think that the objective should be a bit more adjusted to the results, since "effects reported in these studies translate to the general population or even are significant"" is not reflected in the results or indicate in results those countries in which they have not identified any initiative.
In the methodology, the reviewers indicate the use of inclusion and exclusion criteria. They should be indicated.
The discussion is the most interesting section of this work, I think it provides a vague reflection on the subject. However, you should be careful with how you consider your information collection "robust", I do not think so.
In sum, although many issues would be resolved by careful proofreading, the manuscript needs a careful evaluation of data quality beyond applied methodology. In other words, do we have enough data to arrive to strong conclusions?
Author Response
Thank you for allowing me to review the article "Alternative Options for Complex, Recurrent Pain States: A Narrative Review of Clinical Evidence ".
The study evaluated chronic pain management with alternative
and combinations of medications in the treatment of chronic pain. The authors conducted an extensive and careful review of the literature following standard bibliography evaluation guidelines. The conclusion of the study is that chronic pain management is a complex problem across healthcare and is a significant factor in the quality of life for individuals affected
While strong methodologically, the manuscript does not deliver a clear message in key sections because of grammar weaknesses (e.g., awkward sentences). The first paragraph of the Discussion is particularly problematic and less impactful than the last two sentences of the Abstract. There are also typo errors.
Answer: This has been looked over and revised
It is an original work, very ambitious and of great importance in public health.
The title should be adjusted to the content of the work.
Answer: This has been revised
I think that the objective should be a bit more adjusted to the results, since "effects reported in these studies translate to the general population or even are significant"" is not reflected in the results or indicate in results those countries in which they have not identified any initiative.
Answer: This has been revised but let us know if we’re not fully understanding your suggestion so we can make further edits.
In the methodology, the reviewers indicate the use of inclusion and exclusion criteria. They should be indicated.
Answer: This has been included.
The discussion is the most interesting section of this work, I think it provides a vague reflection on the subject. However, you should be careful with how you consider your information collection "robust", I do not think so.
Answer: This has been revised
In sum, although many issues would be resolved by careful proofreading, the manuscript needs a careful evaluation of data quality beyond applied methodology. In other words, do we have enough data to arrive to strong conclusions?
Answer: There really isn’t so this has been revised
Round 2
Reviewer 1 Report
The authors gave little consideration to the reviewer's suggestions.
Reviewer 3 Report
The manuscript reads much better and I am happy to recommend it for publication.
Good luck to you all!
