The Rationale for the Automation of a New Diagnostic Thermography Protocol to Confirm a Chronic-Low-Back-Pain Subtype Related to Nociplastic Pain
Round 1
Reviewer 1 Report
Parts of the introduction appear repetitive (same or similar sentences/concepts repeated, or definitions re-stated), Duplicative or very similar sentences/concepts need to be removed. Organization could be improved especially in sections 1 & 2.
Line 61 -You may wish to add a phrase in this sentence about regarding poor reliability/reproducibility of palpatory measures
Describe the differences between sciatica and gluteal syndrome. How would these be differentially diagnosed? Wouldn’t sciatica automatically engulf gluteal syndrome? Clarify differences (do not just say “mimics”)
Line 68 & 269-Please clarify whether MPI is nociceptive needling or involves any other transitory noxious stimulation. If needling is the accepted noxious stimulation method of choice, I recommend using the term nociceptive needling throughout as it is more descriptive than minimally invasive procedure (which encompass a host of different surgical and non-surgical procedures).
Line71-73- and Line 219 you mention the newest findings but references are from 2004, 2004, 2013, 2017. I am not sure “newest findings” or recent findings is appropriate.
Line 105 If central sensitization is difficult to evaluate as manifestations vary from condition to condition, how would nociplastic pain be any easier?
Line 166 List all 5 stages
Line 218-Clarify why was “ANS involvement measurement in pain states was abandoned some time ago”, was it just a transitory outcome, with no reliability at various time points even within the same individuals?
Line 230-Clarify vagal control/regulation of gluteal blood supply
Line 252-Can thermography identify individual trigger points or just larger temperature asymmetries? This limitation should be recognized, as it is one thing to identify a breast tumor vs much smaller active trigger points using thermography.
Line 295-296. 10 minutes after nociceptive stimulation has ended and then 6 minutes post-stimulation (would not the 6 minutes post-stimulation be included in the 10 minutes after nociceptive stimulation?), Please clarify.
Line 31-319. Should not the need for ROI standardization be emphasized more, and just standardization of thermography procedures analysis in general. Have standards been developed and if so are they accepted and adhered to? Is not this the first step needed?
Lines 307- 348. Present the methodology of automated quantitative analysis in a clearer format. Are the authors proposing a new method of analysis in contrast to previous methods of analysis, if so this needs to be clearer and more detailed for the reader.
The limitation section brings to light some key reasons by thermography has fallen out of favor, can any solutions be offered in overcoming these problematic limitations of using thermography on a greater scale clinically?
Discussion- not all active or latent Trigger points lead to central sensitization, yet all active Trigger points should stimulate C-fiber activation, and yet doesn’t lead to nociplastic pain. This point could be better addressed.
The conclusion needs to be strengthened and does not mention thermography which is key to this entire MIP analysis.
Author Response
Thank you for your time and effort to review our paper. We would like to underline that your comments were the most useful and detailed and they have influenced the final paper the most.
We believe that we have corrected the paper following most of your suggestions.
“Parts of the introduction appear repetitive (same or similar sentences/concepts repeated, or definitions re-stated), Duplicative or very similar sentences/concepts need to be removed. Organization could be improved especially in sections 1 & 2.”
All the repetitions have been removed. Section 1 has been significantly corrected based on both reviewers’ comments. What we consider to be the most important is to underline that we present a new diagnostic method. The MIP protocol is a proposal of a completely new approach in medical thermography. It is similar to ADT protocols but it has some basic differences. Generally, the MIP allows registering the pathological ANS activity, which can help characterize a certain subpopulation of pain patients. This autonomic phenomenon is a new biological finding specific for trigger points exclusively.
“Line 61 -You may wish to add a phrase in this sentence about regarding poor reliability/reproducibility of palpatory measures”
We have added some proper sentences.
“Describe the differences between sciatica and gluteal syndrome. How would these be differentially diagnosed? Wouldn’t sciatica automatically engulf gluteal syndrome? Clarify differences (do not just say “mimics”)”
Gluteal syndrome has been better described and some important information has been added.
“Line 68 & 269-Please clarify whether MPI is nociceptive needling or involves any other transitory noxious stimulation. If needling is the accepted noxious stimulation method of choice, I recommend using the term nociceptive needling throughout as it is more descriptive than minimally invasive procedure (which encompass a host of different surgical and non-surgical procedures).”
Although currently we are using the term minimally invasive procedure to describe our method, its final name is supposed to be invasive-Active Dynamic Thermography (i-ADT), as proposed in our newly submitted grant application. The grant is aimed at developing the MIP protocol according to the ADT requirements. However, we will be able to use that name only after the protocol has been developed. Please note that the method was patented under the name Thermovision Technique of Dry Needling, which we then changed in some subsequent papers to Minimally Invasive Procedure, which is more descriptive. Of course, we agree that the term minimally invasive procedure can have both surgical and non-surgical connotations. However, we’d rather not introduce any other description for our method because we have two quite recent papers already published where the MIP term is used.
“Line71-73- and Line 219 you mention the newest findings but references are from 2004, 2004, 2013, 2017. I am not sure “newest findings” or recent findings is appropriate.”
We were indeed not precise enough. The corrected sentence is now: The ANS involvement measurement in any pain states, e.g., to measure pain severity, has been abandoned some time ago.
Instead of “Although formerly the ANS measurement in pain states was considered to be of limited use, the newest findings have suggested that provocative tests allow the observation of a transient ANS imbalance [18-21].
“Line 105 If central sensitization is difficult to evaluate as manifestations vary from condition to condition, how would nociplastic pain be any easier?”
We hope that the rewritten Section 1 can now better explain the idea of the paper, which was to describe the MIP as a possible new tool to confirm some subtypes of nociplastic pain. The whole scientific audience is looking for one tool to confirm this complicated state with a lot of clinical variabilities. Our idea is to look from the other side. We want to check if focusing step by step on different diseases classified as nociplastic pain by examining the ANS involvement can allow us to find some plausible solutions.
“Line 166 List all 5 stages”
The list has been provided as requested.
Line 218-Clarify why was “ANS involvement measurement in pain states was abandoned some time ago”, was it just a transitory outcome, with no reliability at various time points even within the same individuals?
Diagnosing patients using thermography or the HRV measurement is thought to be objective but for a limited population of patients, e.g. for neuropathic patients, a thermographic camera can point to the ANS involvement in some diseases or conditions. Moreover, the results of the studies on the ANS did not correlate with the patients’ level of pain or their clinical state. That is why the ANS measurement was assumed to be of scarce utility as regards the general patient population.
The MIP is a new method of the ANS measurement focused on the confirmation of disturbed ANS functioning probably related to the central sensitization process considered to be a new promising direction for CS-related pain diagnosis.
“Line 230-Clarify vagal control/regulation of gluteal blood supply”
Please note that the revised version has clarified that the MIP is intended to confirm any pain syndrome related to muscles, not gluteal syndrome only. It has been confirmed that around 30% of chronic tendinopathies, osteoarthritis patients, etc. are influenced by active trigger points. The HRV measurement was indicated as a possible tool for other muscles presenting central sensitization
However, we understand why you are asking about the link between the vagal nerve and gluteal blood supply, which is not existing. Your question indicates to us that Section 3 can be misleading to the readers and so we have moved it as part 2 describing a potential role of the autonomic nervous system in nociplastic pain.
“Line 252-Can thermography identify individual trigger points or just larger temperature asymmetries? This limitation should be recognized, as it is one thing to identify a breast tumor vs much smaller active trigger points using thermography.”
We hope that the information provided in the revised Section 1 has clarified that the MIP is focused on confirming the autonomic phenomenon within the referred pain zone. We definitely agree that the diagnostic value of medical thermography used in the past to confirm trigger points localization is not convincing.
“Line 295-296. 10 minutes after nociceptive stimulation has ended and then 6 minutes post-stimulation (would not the 6 minutes post-stimulation be included in the 10 minutes after nociceptive stimulation?), Please clarify.”
The MIP is a new protocol that is developed step by step based on the new studies. The time of the post-stimulation phase was established in the pilot study, which indicated the time of the maximum duration of the autonomic referred pain development. Currently, to improve the protocol according to the ADT protocols, we need to define the minimum duration of the noxious stimulation that would allow the observation of the significant vasomotor changes. Then, we need to define the time of the post-observation phase which would allow us to observe the patients’ return to the norm (state before stimulation).
“Line 31-319. Should not the need for ROI standardization be emphasized more, and just standardization of thermography procedures analysis in general. Have standards been developed and if so are they accepted and adhered to? Is not this the first step needed?”
In the new version, a more detailed explanation has been provided. A new paper considering the first terms of the method’s automation (Skorupska et al. Brain Sciences) has been recently published. The revised version was rewritten after the publication. We have noticed that because our approach uses lots of different innovations, it can confuse the readers. They mostly consider our method to be a side-to-side comparison focused on trigger points localization. However, it is not how our method should be viewed. The current paper underlines the new solutions applied to the MIP (listed above).
“Lines 307- 348. Present the methodology of automated quantitative analysis in a clearer format. Are the authors proposing a new method of analysis in contrast to previous methods of analysis, if so this needs to be clearer and more detailed for the reader.”
A full description is provided within the new paper [Brain Sciences].
“The limitation section brings to light some key reasons by thermography has fallen out of favor, can any solutions be offered in overcoming these problematic limitations of using thermography on a greater scale clinically?”
Limitations
A disadvantage of the MIP is painful stimulation, which is necessary to provoke pathological ANS reactivity within trigger points referred pain. The minimum time of noxious stimulation and the time of the observation phase need to be defined to build a precise protocol according to the Active Dynamic Thermography requirements.
We have provided a detailed explanation within the text on how much the MIP differs from other studies considering medical thermography. The key is the registration of the new biological phenomenon limited to a specific disease, its size calculation together with the temperature measurement. We believe that the revised version will now better underline that.
“Discussion- not all active or latent Trigger points lead to central sensitization, yet all active Trigger points should stimulate C-fiber activation, and yet doesn’t lead to nociplastic pain. This point could be better addressed.”
The state-of-the-art knowledge about trigger points suggests that active trigger points are related to central sensitization. According to scientific data, two trigger points features suggest the CS involvement, namely (i) the lowering of the pressure pain thresholds in the vicinity of TrPs, and (ii) the presence of referred pain. Thus, it seems that not every TrP confirmed by Travell and Simons criteria can be defined as related to CS. However, the newly revised clinical criteria indicate the necessity of the referred pain presence to confirm every active and latent trigger point. The subgroups of patients diagnosed according to these criteria can be defined as related to CS. Until now, the MIP considered only trigger points with the referred pain presence. It is not known how latent trigger points or active TrPs that do not present referred pain would react to the MIP. If the MIP-provoked autonomic phenomenon characterized only those TrPs that present referred pain, the method would support the newly proposed TrPs clinical criteria and could become an objective diagnostic tool to confirm them.
We have provided this assumption within the text.
“The conclusion needs to be strengthened and does not mention thermography which is key to this entire MIP analysis”.
The new version of the conclusions:
The minimally invasive procedure is intended to confirm a completely new biological phenomenon, which suggests a pathological autonomic response to noxious stimuli and can possibly become an objective marker of the central sensitization process related to muscles . It applies a new type of the active dynamic thermography method and uses invasive nociceptive muscle stimulation for the first time. The MIP protocol is based on the analysis of one side only and focused on the confirmation or not of a pathological autonomic phenomenon occurrence within the perceived pain zone. Furthermore, automated thermogram picture segmentation is performed to confirm the pathology. Finally, the diagnosis is based on the analysis of all 320 thermograms using MATLAB. The first pain syndrome examined by the MIP is a new subtype of low back pain, namely gluteal syndrome. Further studies con-sidering the examination of other pain syndromes related to trigger points by the MIP supported by MATLAB are recommended.
Authors,
Reviewer 2 Report
Thank you for permitting me to review this manuscript
Here are my comments
Line 77
I suggest : Background for method application instead of "biological"
Line 92, 96 Please provide reference (PPR)
Line 100 please insert patients with gluteal syndrome presents...
PPR Line 102
Line 107 124 Please rephrase in a more clear text , right now it is confusing
Table 1 where is the topdown syndrome in this table ?
Line 134-139 PPR
Line 144 PPR
line 168-174-1887 PPR
Page 5 please focus on the rationale of this new technique and skip details not related to the subject
Page 6
Please
enumerate advantages of the technique over other meaans of diagnosis
Figure 1
Please provide an iconography with more legend , right now the legend is totally unreadable
A photo of the device is welcomed
Matlab should be detailed , which version , which country etc...
Line 327- 331- PPR
Please explain clearly in details how the new device would differentiate the gluteus syndrome with other syndromes?
Author Response
Thank you for your time and effort to review our paper. We would like to underline that your comments were the most useful and detailed and they have influenced the final paper the most.
We believe that we have corrected the paper following most of your suggestions.
Here are my comments
Line 77 “I suggest : Background for method application instead of "biological"
Recently, we have published a new paper on the MIP automation (Skorupska et al. 2021 Brain Sciences). The next three are under editorial consideration. In the review process, it was brought to our attention that the innovative elements of our method are not easy to follow. Thus, in the current version of this reviewed paper, it has been underlined that
That is why we feel that it is important to present the biological aspects that can explain the mechanisms of the occurrence of the pathological ANS response to the nociceptive stimulus.
“Line 92, 96 Please provide reference (PPR)”
The references have been provided (line 71).
“Line 100 please insert patients with gluteal syndrome presents...”
This paragraph is about patients with nociplastic pain related to muscle, not only gluteal syndrome.
“PPR Line 102”
The references have been provided (line 139)
Line 107 124 Please rephrase in a more clear text , right now it is confusing
The new version is
In the “bottom-up” CS mechanism pain is said to be perceived due to an excess noxious periph-eral input that eventually sensitizes the central nervous system to the point of perceiving pain. Over time, pain is perceived even when there is no peripheral drive. The “top-down” theory suggests that changes already present within the central nervous system drive the perception of pain, the primary problem may very likely originate in supraspinal structures, and no ongoing nociceptive input is required to maintain the process. Female predisposition is common for both CS mechanisms. Otherwise, the mechanisms differ. To illustrate the difference, patients manifesting the “top-down” subtype can have a family history of pain, high psychological co-morbidity, increased sensitivity to non-pain sensory stimuli, a high number of chronic over-lapping pain conditions, and the beginning of their symptoms is associated with puberty. Pa-tients with the “bottom-up” subtype are generally less burdened. The most important dif-ference between the two subtypes of CS mechanism is that “bottom-up” is thought to be a re-versible process, contrary to irreversible “top-down”. Because of its reversible nature, the “bot-tom-up” CS subtype seems particularly interesting. Muscle pain related to trigger points pres-ence seems to be an example of this CS subtype. If the hypothesis about the “bottom-up” and “top-down” CS mechanisms is true, patients with different CS subtypes will need different treatment. The similarities between trigger points and both subtypes of central sensitization are shown in Table 1.
Table 1 where is the topdown syndrome in this table ?
The top-down feature has been added.
Line 134-139 PPR
The references have been provided (line 181).
Line 144 PPR
The references have been provided (line 211).
line 168-174-1887 PPR
The references have been provided (213, 220, 232).
Page 5 please focus on the rationale of this new technique and skip details not related to the subject
We hope that you will find the changes satisfying
Page 6
Please enumerate advantages of the technique over other meaans of diagnosis
We have underlined the meaning of our method of the method.
Figure 1
Please provide an iconography with more legend, right now the legend is totally unreadable
A new figure and the legend has been provided.
Figure 1. An illustration of the minimally invasive procedure (MIP) applied to a gluteus syn-drome case (vasodilatation) and a chronic sciatica case (lack of a significant vasomotor reactivity ).
Legend: (I) gluteus minimus referred pain pattern established by Travell and Simons based on the post-stimulation reports of the patients with gluteus minimus trigger points (not objectively confirmed); (II) diagnostic protocol; (III) examples of the registered 320 MIP thermograms (a) pictures of a patient without noxious stimulation; (b) pictures showing positive MIP results – a registered pathological ANS activity within the patient’s perceived pain zone; c) pictures show-ing negative MIP results – lack of a pathological ANS activity within the patient’s perceived pain zone; (color picture – full range of temperature; gray picture – individually isolated state above the maximum temperature at rest).
A photo of the device is welcomed
The diagnostic protocol and a new autonomic phenomenon occurrence and its numerical calculation are the new things. We used a standard IRT camera. We have changed Figure 1 to underline that.
Matlab should be detailed , which version , which country etc...
The information has been provided according to the MATALB version used in our new study.
Line 327- 331- PPR
The references have been provided (lines 380, 384).
Please explain clearly in details how the new device would differentiate the gluteus syndrome with other syndromes?
The occurrence of the phenomenon exceeding the patients’ temperature at rest and covering the painful area (e.g. thigh, calf) is the aim of the method. It is specific for trigger points only. It has not been observed in any other pain states or healthy subjects as a result of muscle noxious stimulation. The new version of Figure 1 underlines the differences between sciatica and gluteus syndrome patients.
Authors,
Round 2
Reviewer 1 Report
The reviewer comments have been adequately addressed. Minor changes in sentence structure and/or more formal word choice among the red text would be of benefit.
Author Response
The selected fragments have been proofread.
Reviewer 2 Report
The authors have significantly improved the manuscript
figure 1 police is still too small and it is unreadable it needs A3 format to be readable therefore I recommend to use greater police for the figure it self
however the legend is ok
Author Response
Figure 1 has been reorganized, improved, and made more readable.
