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Peer-Review Record

Perceived Pain in People Living with Amyotrophic Lateral Sclerosis—A Scoping Review

Nurs. Rep. 2024, 14(4), 3023-3039; https://doi.org/10.3390/nursrep14040220
by Debora Rosa 1, Laura Ingrande 1, Ilaria Marcomini 1, Andrea Poliani 1, Giulia Villa 1,*, Martina Sodano 2 and Duilio Fiorenzo Manara 1
Reviewer 1:
Reviewer 2: Anonymous
Reviewer 3: Anonymous
Nurs. Rep. 2024, 14(4), 3023-3039; https://doi.org/10.3390/nursrep14040220
Submission received: 27 June 2024 / Revised: 12 October 2024 / Accepted: 14 October 2024 / Published: 17 October 2024

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

nursrep-3101891

This is a formal literature review of pain in patients with ALS, asking about what is the impact, how is it perceived and what are its characteristics?  The methodology is reasonable, the manuscript is clearly written, and overall, the study is a reasonable exercise. 

While the English is very readable there are places where it is somewhat overwritten, specifically in the Introduction where the data on incidence is not germane to the study.

As a comment, the major issues could be anticipated that the data would be disparate over how pain is asked about and medications tried with varying amounts rigor, and at the end of the literature review very little is learned that can be applied – perhaps this is the goal of the study hopefully leading to more focused research, but it asks the question of whether the authors will perform a study with greater rigor?  There also seems to be a searching for a particular type of pain, perhaps unique to ALS, but most of the pain described by ALS patients is related to relative immobility and its consequences and less commonly to something unique, and similarly, not sure that there will be a unique medicine with specific effectiveness.

Author Response

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Reviewer 2 Report

Comments and Suggestions for Authors

The authors analyzed how people with ALS experience pain, and how this affects their daily activities and social relationships by using a Scoping Review.

The paper is impeccable, following well-conducted and justified procedures in accordance with the guidelines. But I have a few concerns.

1.  A major concern is how to ensure the validity of the current outcomes (headings) in light of the purpose of PERCEIVE PAIN. That is, whether the current eight headings of pain expression, pain intensity, pain location, pain management, impact of pain on activities of daily living (ADL), impact of pain on social relationships, relationship between pain and other conditions, and pain and palliative care, are sufficient. For example, pain is said to have physical, mental, social, and spiritual aspects. The question is whether these aspects are fully expressed in terms of expression, intensity, and location, or whether the differences in pain over the course of ALS are adequately described. It would be better if it were explained how these headings were derived from the literature search. 

  the following are minor points.

2 .  P3 table 1 In the PCC, is there any mention of the relevant context in the PCC?

3.  P4Fig 1 In PRISMA flow, there are some missing figures, which should be filled in.

(Report assessed for eligibility=55 and Report of included studies=13)

4.  Is there any regularity in the order in which the references are listed in Table 2 Data extraction? In tables 3 and 4, the authors are in alphabetical order.

Author Response

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Reviewer 3 Report

Comments and Suggestions for Authors

This article provides a valuable synthesis of the existing literature on pain in ALS patients. The use of a scoping review approach is appropriate for an area where empirical research is sparse. However, several aspects of the study could be improved:

  1. Scope and Depth: Although the scoping review covers important ground, the selection of only 13 articles limits its scope. Expanding the review to include more recent research or grey literature could provide a fuller picture. Moreover, while the study focuses on spinal/bulbar ALS, it does not deeply explore potential differences between these subtypes in terms of pain perception and treatment. Further research should investigate how pain manifests differently depending on ALS phenotypes and stages, which could lead to more personalized and effective management strategies.
  2. Pain Mechanism and Treatment: While the article identifies the prevalence and impact of pain in ALS patients, it provides insufficient discussion of the multidimensional nature of pain in ALS. Pain in ALS is not solely nociceptive or mechanical but can have neuropathic and sensory dimensions as well (DOI: 10.1016/S1474-4422(16)30358-1). This multidimensional aspect includes sensory disturbances that have been recently demonstrated through skin biopsy studies, showing the degeneration of small nerve fibers in ALS patients. These sensory alterations, often under-recognized, suggest that ALS is not purely a motor neuron disease but also involves a sensory component (https://doi.org/10.1093/brain/awad426),.
  3. In addition, there is growing evidence of interoceptive dysfunction in ALS patients, where the body's ability to perceive and integrate internal physiological signals, such as heart rate or respiration, becomes impaired. Interoception, crucial for the experience and modulation of pain, is altered in ALS, potentially leading to an impaired perception of pain stimuli. This could cause patients to either underreport pain or experience pain differently, making it more challenging to assess and treat. Interoceptive dysfunction might also affect emotional responses to pain, as the brain integrates interoceptive signals when processing discomfort and other somatic sensations. Therefore, the article would benefit from a more detailed exploration of how interoceptive alterations (doi: 10.1007/s10072-022-06231-4) influence pain perception and complicate the communication of pain in ALS patients. Recognizing these factors would push clinicians to employ more sensitive and multidimensional tools for pain assessment.
  1. Critical Analysis: While the article does an excellent job of summarizing data, it lacks a deeper critical analysis of the reviewed studies. More attention should be given to methodological weaknesses, regional differences in pain perception, and the specific characteristics of ALS-related pain. Such analysis would give readers a clearer understanding of how to interpret the findings and apply them to clinical practice
  2. Future Directions: The article concludes with a call for improved pain management but does not propose specific directions for future research. The authors should more explicitly outline the gaps in current research and recommend how these gaps could be addressed. For example, future studies should investigate how sensory and interoceptive dysfunctions in ALS contribute to pain perception and management challenges. Developing specific diagnostic tools to assess these dysfunctions could improve pain assessments and treatment plans. Furthermore, exploring non-pharmacological interventions such as physical therapy or cognitive behavioral therapy, which could address both sensory disturbances and interoceptive issues, might offer new avenues for pain relief in ALS patients.

 Minor:

In the introduction, given that pain might be considered a non-motor symptom of the disease, it would be valuable to explore in greater detail other non-motor manifestations and their association with disease progression and survival. Non-motor symptoms, such as cognitive impairments (DOI: 0.1212/WNL.0000000000008063), behavioral disturbances (DOI: 10.1212/WNL.0000000000006317), autonomic dysfunctions (DOI: 10.1007/s00415-023-11832-w), and sensory/painful disorders (https://doi.org/10.1093/brain/awad426), play a significant role in the disease's clinical presentation. These manifestations not only contribute to the overall burden of the disease but may also serve as important indicators of its progression and impact on patient survival.

Author Response

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