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<blockquote>[[File:Question 2.jpg|50x50px|link=https://wiki.masticationpedia.org/index.php/File:Question_2.jpg|left]]'''<math>K_{brain}</math>: The uncertainty of the measurement '''
<blockquote>[[File:Question 2.jpg|50x50px|link=https://wiki.masticationpedia.org/index.php/File:Question_2.jpg|left]]'''<math>K_{brain}</math>: The uncertainty of the measurement '''


All true and, among other things, the arguments are very engaging from an intellectual point of view, but we should take into account the series of assertions such as neuronal convergence, the inhibition of downregulation mechanisms of descending pain,<ref name=":1" /><ref name=":2" /> allodynia,<ref name=":3" /> and the concept of measure that inevitably incorporates an uncertainty. We reported a very interesting study (Exploring electroencephalography with a model inspired by quantum mechanics) which demonstrated the existence of an error in the measurement of the EEG by defining a similar Heisenberg uncertainty principle called 0 quasi-quantum model which led to a constant minimum value of uncertainty in the EEG measurement at 0 and 0 of 0. Note that the unit of 0 is the result of sampling the EEG at 250 Hz and taking mass as the unit. This should make us reflect in interpreting the results of laboratory research because, as we will see in the presentation of subsequent clinical cases, the diagnostic error is around the corner. Enough 0 error in the specific measurement of the neuronal district under examination to make a diagnosis of Orofacial Pain when instead there is a brain tumor that involved the same nervous district and simulates the symptoms of Orofacial Pain from Temporomandibular Disorders.
All true and, among other things, the arguments are very engaging from an intellectual point of view, but we should take into account the series of assertions such as neuronal convergence, the inhibition of downregulation mechanisms of descending pain,<ref name=":1" /><ref name=":2" /> allodynia,<ref name=":3" /> and the concept of measure that inevitably incorporates an uncertainty. We reported a very interesting study ([[Exploring electroencephalography with a model inspired by quantum mechanics]]) which demonstrated the existence of an error in the measurement of the EEG by defining a similar Heisenberg uncertainty principle called <math>K_{brain}</math> quasi-quantum model which led to a constant minimum value of uncertainty in the EEG measurement at <math>\Delta x(t)\Delta p_x(t)</math> and <math>\Delta y(t)\Delta p_y(t)</math> of <math>0,78\pm0,41\tfrac{cm^2}{4ms}</math>. Note that the unit of <math>\tfrac{cm^2}{4ms}</math> is the result of sampling the EEG at 250 Hz and taking mass as the unit. This should make us reflect in interpreting the results of laboratory research because, as we will see in the presentation of subsequent clinical cases, the diagnostic error is around the corner. Enough <math>0,78\pm0,41\tfrac{cm^2}{4ms}</math> error in the specific measurement of the neuronal district under examination to make a diagnosis of Orofacial Pain when instead there is a brain tumor that involved the same nervous district and simulates the symptoms of Orofacial Pain from Temporomandibular Disorders.


</blockquote>Therefore, objectivity, scientific humility and a change of mindset in the interpretation of biological phenomena are needed, a topic that we will address in the 'Extraordinary Science' section At this stage, however, it is advisable to sort out the contents by resuming the already anticipated references regarding the classification of Orofacial Pain and DTM but in a more specific way to address the clinical cases to follow. Temporomandibular disorders (TMD) are a group of musculoskeletal and neuromuscular conditions affecting the masticatory muscles, temporomandibular joint (TMJ) and other associated structures.<ref name=":4" /> According to the diagnostic criteria for TMD (DC/TMD), as already reported, in 'Axis I', TMD could be divided into intra-articular disorders, including disc displacement, arthralgia, arthritis and osteoarthritis, and muscle disorders.<ref name=":4" /> The latter are also referred to as “myogenic TMDs”, which can be further classified into: local myalgia, if the pain is localized on palpation; myofascial pain, if the pain spreads within the palpated muscle territory; and myofascial pain with referral, if the pain spreads beyond the border of the masticatory muscles.<ref name=":4" />


Tutto vero e tra l'altro molto coinvolgenti gli argomenti da un punto di vista intellettuale ma bisognerebbe tener in conto delle serie di asserzioni poste come la convergenza neuronale, l'inibizione dei meccanismi di downregulation del dolore discendente, la allodinia, ed il concetto di misura che inevitabilmente incorpora una incertezza. Abbiamo riportato uno studio ([[Esplorare l'elettroencefalografia con un modello ispirato alla meccanica quantistica]])  molto interessante che ha dimostrato l'esistenza di un errore nella misura dello EEG definendo un analogo principio di indeterminazione di Heisenberg denominato <math>K_{brain}</math> modello quasi-quantistico che ha portato a un valore minimo costante di incertezza nella misura EEG  su <math>\Delta x(t)\Delta p_x(t)</math> e<math>\Delta y(t)\Delta p_y(t)</math> di <math>0,78\pm0,41\tfrac{cm^2}{4ms}</math>. Si noti che l'unità di <math>\tfrac{cm^2}{4ms}</math> è il risultato del campionamento dell'EEG a 250 Hz e della massa considerata come unità.
<blockquote>[[File:Question 2.jpg|50x50px|link=https://wiki.masticationpedia.org/index.php/File:Question_2.jpg|left]][[File:Hephaptic edited.jpeg|thumb|200x200px|'''Figure 1:''' Trasmissione efaptica|link=https://wiki.masticationpedia.org/index.php/File:Hephaptic_edited.jpeg]]'''Machine language logic'''  


Ciò ci dovrebbe far riflettere nel interpretare i risultati delle ricerche di laboratorio perchè, come vedremo nella presentazioni dei successivi casi clinici, l'errore diagnostico è dietro l'angolo. Bastano <math>0,78\pm0,41\tfrac{cm^2}{4ms}</math> di errore nella misura specifica del distretto neuronale in esame per fare una diagnosi di Dolore Orofacciale quando invece si è in presenza di un tumore cerebrale che coninvolgeva lo stesso distretto nervoso e simula la sintomatologia del Dolore Orofacciale da Disordini Temporomandibolari.</blockquote>Ci vuole, dunque, obiettività, umiltà scientifica e un cambio di forma mentis nell'interpretazione dei fenomeni biologici, argomento che affronteremo nella sezione 'Scienza Straordinaria'
With regard to "myogenic TMDs" it is not as simple as the description of the CDR appears because, as we have highlighted for our poor patient '[[Encrypted code: Ephaptic transmission|Mary Poppins]]', the muscle pain and bone deconstruction of the ATM had concealed, in a logic of classical language, a much more serious organic damage that beyond the classifications it was possible to resolve, after 10 years of pilgrimage among various specialists. Only by acquiring a machine language logic was it possible to interpret the encrypted code of the 'Ephaptic Transmission'. (Figure 1) Having said this, classifications are welcome but not the use of a verbal language logic which remains, however, a vague phenomenon and ambiguous. Formal language logics such as mathematics are certain in the sense that equation <math>x^2=-1</math> has no solutions in the set of real numbers, because in this set there are no numbers whose square is negative. The value <math>i</math> is then defined, called the imaginary unit, which has the following property: <math>i^2=-1.</math> The equation <math>x^2=\pm1</math> does not exist in mathematics as it does in medical diagnostics. Without going into overly specialized topics which, however, we will address in the 'Extraordinary Science' section, in a logic of verbal language the uncertainty is much higher than that which occurs in a logic of machine language because Poppins could be affected (as they are things went) from myalgia, TMD, vasculitis, Morphea or from hemimasticatory spasm while the 'Ephaptic transmission' remains forever an organic damage and the clinical interpretation cannot be dichotomous as <math>1^2</math> cannot be <math>\pm1</math> but only <math>-1</math>. 


In questa fase, però, è opportuno fare un pò di ordine dei contenuti riprendendo i riferimenti già anticipati riguardo alla classificazione del Dolore Orofacciale ed DTM ma in modo più specifico per affrontare i casi clinici a seguire.
</blockquote> 


I disturbi temporomandibolari (TMD) sono un gruppo di condizioni muscoloscheletriche e neuromuscolari che colpiscono i muscoli masticatori, l'articolazione temporomandibolare (TMJ) e le altre strutture associate.<ref name=":4" /> Secondo i criteri diagnostici per il TMD (DC/TMD), come già riportato, nello  'Asse I', il TMD potrebbe essere suddiviso in disturbi intra-articolari, tra cui spostamento del disco, artralgia, artrite e artrosi e disturbi muscolari.<ref name=":4" /> Questi ultimi sono definiti anche “TMD miogeni”, che possono essere ulteriormente classificati in: mialgia locale, se il dolore è localizzato durante la palpazione; dolore miofasciale, se il dolore si diffonde all'interno del territorio muscolare palpato; e dolore miofasciale con rinvio, se il dolore si diffonde oltre il confine dei muscoli masticatori.<ref name=":4" /> <blockquote>[[File:Question 2.jpg|50x50px|link=https://wiki.masticationpedia.org/index.php/File:Question_2.jpg|left]][[File:Hephaptic edited.jpeg|thumb|200x200px|'''Figure 1:''' Trasmissione efaptica|link=https://wiki.masticationpedia.org/index.php/File:Hephaptic_edited.jpeg]]'''Logica di linguaggio macchina'''
A recent systematic review and meta-analysis, with a combined sample of 2518 subjects, suggested that the prevalence of TMD could range from 25.2% to 34.9%,<ref>Bueno C.H., Pereira D.D., Pattussi M.P., Grossi P.K., Grossi M.L. Gender differences in temporomandibular disorders in adult populational studies: A systematic review and meta-analysis. J. Oral Rehabil. 2018;45:720–729. doi: 10.1111/joor.12661</ref> with a predominance of the myofascial pain diagnosis (10.3- 15.4%) [2]. While a study by Javed Ashraf et al.<ref name=":6">Javed Ashraf,Matti Närhi, Anna Liisa Suominenand  Tuomas Saxlin. Association of temporomandibular disorder-related pain with severe headaches—a Bayesian view. Clin Oral Investig. 2022; 26(1): 729–738. Published online 2021 Jul 5. doi: 10.1007/s00784-021-04051-y. PMCID: PMC8791898. PMID: 34224000
</ref> using Bayesian methodology, aimed to examine the association of TMD-related pain with severe headaches (migraine and TTH) over an 11-year follow-up period compared with the frequency approach. Frequentist statistics suffer from some limitations, most notably the reliance on large sample sizes to accurately determine effect sizes.<ref name=":5">Buchinsky FJ, Chadha NK. To P or not to P: backing Bayesian statistics. Otolaryngol Head Neck Surg. 2017;157(6):915–918. doi: 10.1177/0194599817739260</ref> Furthermore, contrary to the Frequentist methodology, Bayesian statistics do not provide a (fixed) result value but rather an interval containing the regression coefficient.<ref>Depaoli S, van de Schoot R. Bayesian analyses: where to start and what to report. Eur Heal Psychol. 2014;16:75–84.</ref> These intervals, called credible intervals (CI), place a probability on the best estimate among all possible values of the parameter estimates.<ref name=":5" />


Riguardo ai “TMD miogeni” non è così semplice come appare alla descrizione dello RDC perchè come abbiamo evidenziato per la nostra povera paziente '[[Codice criptato: Trasmissione efaptica|Mary Poppins]]' il dolore muscolare ed la destrutturazione ossea dell'ATM aveva occultato, in una logica di linguaggio classica, un danno organico molto più grave che al di là delle classificazioni si è potuto risolvere, dopo 10 anni di pellegrinaggio tra specialisti vari. Soltanto acquisendo una logica di linguaggio macchina si è potuto interpretare il codice criptato della 'Trasmissione Efaptica'.(Figura 1) Detto questo ben vengano le classificazione ma non l'utilizzo di una logica di linguaggio verbale che rimane, comunque, un fenomeno vago ed ambiguo. Le logiche di linguaggio formali come quella matematica è certa nel senso che l'equazione <math>x^2=-1</math> non ha soluzioni nell'insieme dei numeri reali, perché in questo insieme non esistono numeri il cui quadrato sia negativo. Si definisce allora il valore <math>i</math>, chiamato unità immaginaria, che gode della seguente proprietà: <math>i^2=-1.</math> Non esiste in matematica l'equazione <math>x^2=\pm1</math> come invece succede nella diagnostica medica. Senza entrare in argomenti troppo specialistici che, comunque, affronteremo nella sezione 'Scienza Straordinaria' in una logica di linguaggio verbale l'incertezza è molto superiore a quella che si verifica in una logica di linguaggio macchina perchè la Poppins poteva essere affetta ( da come sono andate le cose) da mioalgia, DTM, vasculite, Morfea oppure da spasmo emimasticatorio mentre la 'Trasmissione efaptica' e rimane per sempre un danno organico e l'imterpretazione clinica non può essere dicotomica come <math>1^2</math> non può essere <math>\pm1</math>.
<blockquote>[[File:Question 2.jpg|50x50px|link=https://wiki.masticationpedia.org/index.php/File:Question_2.jpg|left]]'''Quantum Probability'''  


</blockquote> 
We agree with the considerations that emerged in the study by Buchinsky et al.<ref name=":6" /> because perhaps or fortunately we will never be able to create a formal language logic such as mathematics given the intrinsic randomness of biological models. Even the Bayes models, however, incorporate a conceptual limit which, if exceeded, would improve the probabilistic data and contextually the predictive value <math>P(M|Pos)
 
</math> in the output. Briefly, Bayes' formula looks like this:
Una recente revisione sistematica e meta-analisi, con un campione combinato di 2518 soggetti, ha suggerito che la prevalenza di TMD potrebbe variare dal 25,2% al 34,9%,<ref>Bueno C.H., Pereira D.D., Pattussi M.P., Grossi P.K., Grossi M.L. Gender differences in temporomandibular disorders in adult populational studies: A systematic review and meta-analysis. J. Oral Rehabil. 2018;45:720–729. doi: 10.1111/joor.12661</ref> con una predominanza della diagnosi di dolore miofasciale (10,3-15,4%) [2]. Mentre uno studio di Javed Ashraf et al.<ref name=":6">Javed Ashraf,Matti Närhi, Anna Liisa Suominenand  Tuomas Saxlin. Association of temporomandibular disorder-related pain with severe headaches—a Bayesian view. Clin Oral Investig. 2022; 26(1): 729–738. Published online 2021 Jul 5. doi: 10.1007/s00784-021-04051-y. PMCID: PMC8791898. PMID: 34224000
</ref> utilizzando la metodologia bayesiana, mirava a esaminare l'associazione del dolore correlato a TMD con forti mal di testa (emicrania e TTH) per un periodo di follow-up di 11 anni rispetto all'approccio frequentista. Le  statistiche frequentiste soffrono di alcune limitazioni, soprattutto la dipendenza da grandi dimensioni del campione per determinare con precisione le dimensioni dell'effetto.<ref name=":5">Buchinsky FJ, Chadha NK. To P or not to P: backing Bayesian statistics. Otolaryngol Head Neck Surg. 2017;157(6):915–918. doi: 10.1177/0194599817739260</ref> Inoltre, contrariamente alla metodologia frequentista, le statistiche bayesiane non forniscono un valore di risultato (fisso) ma piuttosto un intervallo contenente il coefficiente di regressione.<ref>Depaoli S, van de Schoot R. Bayesian analyses: where to start and what to report. Eur Heal Psychol. 2014;16:75–84.</ref> Questi intervalli, detti intervalli credibili (CI), attribuiscono una probabilità alla migliore stima tra tutti i possibili valori delle stime dei parametri.<ref name=":5" /> <blockquote>[[File:Question 2.jpg|50x50px|link=https://wiki.masticationpedia.org/index.php/File:Question_2.jpg|left]]'''Probabilità quantistica'''
 
Siamo d'accordo con le considerazione emerse nello studio di Buchinsky et al.<ref name=":6" /> perchè forse o per fortuna non saremo mai in grado di realizzare una logica di linguaggio formale come la matematica visto l'aleatorietà intrinseca dei modelli biologici. Anche i modelli di Bayes, però, incorporano un limite concettuale che se superato migliorerebbe il dato probabilistici e contestualmente il valore predittivo <math>P(M|Pos)
</math> in uscita. In breve la formula di Bayes appare sotto questa forma:


<math>P(M|Pos)=\frac{P(Pos|M)\cdot P(M)}{P(Pos|M)\cdot P(M)+P(Pos|S)\cdot P(S)}
<math>P(M|Pos)=\frac{P(Pos|M)\cdot P(M)}{P(Pos|M)\cdot P(M)+P(Pos|S)\cdot P(S)}
</math>
</math>


Si può quindi notare che per calcolare il valore predittivo del test occorre conoscere anche la probabilità  '''con cui la malattia colpisce la popolazione complessiva <math>P(M)</math>'''. Pertanto un buon test è un test con sensibilità e specificità molto vicine a <math>1</math> a sappiamo tutti che questo è impossibile ed anche sbagliato per certi versi, però, risulterebbe un test paradigmatico. Lo scarso valore aggiunto, in termini di informazione, che i marcatori tumorali, per esempio, forniscono alla diagnosi, rappresenta il razionale per cui se ne sconsiglia l’uso come test di screening in una popolazione non selezionata. Lo stesso potrebbe succedere per i valori predittivi riguardo la TMD culminando in una massiva classificazione di malati ed una inevitabile ricerca della verità da parte del progetto RDC.  
It can therefore be noted that in order to calculate the predictive value of the test, it is also necessary to know the probability with which the disease affects the overall population '''<math>P(M)</math>'''. Therefore, a good test is a test with sensitivity and specificity very close to 0 and we all know that this is impossible and even wrong in some ways, however, it would be a paradigmatic test. The scarce added value, in terms of information, that tumor markers, for example, provide for diagnosis, represents the rationale for which their use as a screening test in an unselected population is not recommended. The same could happen for predictive values regarding TMD culminating in a massive classification of patients and an inevitable search for the truth by the RDC project.  


Senza entrare in argomenti specialistici cerchiamo di descrivere brevemente il razionale di questa affermazione facendo notare, principalmente le differenze tra una modello probabilistico classico e quantistico.( per maggiori informazioni ma molto specialistiche vedi '[[Modellazione quantistica in biologia con sistemi e strumenti quantistici aperti]]')
Without going into specialized topics, we try to briefly describe the rationale for this statement by pointing out, mainly, the differences between a classical and a quantum probabilistic model. (for more but very specialized information, see '[[Quantum-like modeling in biology with open quantum systems and instruments]]')  


Pertanto, nella probabilità claccisa (CP) la distribuzione di probabilità <math>B</math> può essere calcolata dalla probabilità <math>A</math> e dalle probabilità condizionate <math>P(B=\beta|A=\alpha)</math>. Nella probabilità quantistica (QP), laFormula delle Probabilità Totali    (FTP) classico è perturbato dal termine di interferenza (Khrennikov, 2010);<ref>Khrennikov A. Ubiquitous Quantum Structure: From Psychology To Finances Springer, Berlin-Heidelberg-New York(2010)</ref> per le osservabili quantistiche dicotomiche <math>A</math> e <math>B</math> di tipo von Neumann, cioè date dagli operatori hermitiani <math>\hat{A}</math> e <math>\hat{B}</math>, la versione quantistica di FTP ha la forma:
Therefore, in the closed probability (CP) the probability distribution <math>B</math> can be computed from probability <math>A</math> and conditional probabilities <math>P(B=\beta|A=\alpha)</math>. In quantum probability (QP), the classical Total Probability Formula (FTP) is perturbed by the interference term (Khrennikov, 2010);<ref>Khrennikov A. Ubiquitous Quantum Structure: From Psychology To Finances Springer, Berlin-Heidelberg-New York(2010)</ref> for the dichotomous quantum observables <math>A</math> and <math>B</math> of von Neumann type, i.e. given by the Hermitian operators <math>\hat{A}</math> and <math>\hat{B}</math>, the quantum version of FTP has the form:


{{:F:Krennikov1a}}<math>+2\sum_{\alpha_1<\alpha_2}\cos\theta_{\alpha_1\alpha_2}\sqrt{P(A=\alpha_1)P(B=\beta|A=\alpha_1)} P(A=\alpha_2)
{{:F:Krennikov1a}}<math>+2\sum_{\alpha_1<\alpha_2}\cos\theta_{\alpha_1\alpha_2}\sqrt{P(A=\alpha_1)P(B=\beta|A=\alpha_1)} P(A=\alpha_2)
P(B=\beta|a=\alpha_2)</math>
P(B=\beta|a=\alpha_2)</math>


Se il termine di interferenza è positivo, allora il calcolo QP genererebbe una probabilità maggiore della sua controparte CP data dal classico FTP. In particolare, questa amplificazione di probabilità è alla base della supremazia del calcolo quantistico. Esistono numerosi dati statistici provenienti dalla psicologia cognitiva, dal processo decisionale, dalla biologia molecolare, dalla genetica e dall'epigenetica che dimostrano che i biosistemi, dalle proteine e cellule (Asano et al., 2015b)<ref>Asano M., Khrennikov A., Ohya M., Tanaka Y., Yamato I. Quantum Adaptivity in Biology: From Genetics To Cognition Springer, Heidelberg-Berlin-New York(2015)</ref> agli esseri umani (Khrennikov, 2010,<ref>Khrennikov A. Ubiquitous Quantum Structure: From Psychology To Finances Springer, Berlin-Heidelberg-New York(2010)</ref> Busemeyer e Bruza, 2012<ref>Busemeyer J., Bruza P. Quantum Models of Cognition and Decision Cambridge Univ. Press, Cambridge(2012)</ref>) usano questa amplificazione ed operano con aggiornamenti non CP. </blockquote>{{q2|Con questa prefazione alquanto coraggiosa e rischiosa abbiamo evidenziato la complessità dei processi e modelli diagnostici specialmente in presenza di patologie multifattoriali come il Dolore Orofacciale ed i DTM che andremo a presentare nei prossimi capitoli }}{{Bib}}
If the interference term is positive, then the QP computation would generate a higher probability than its CP counterpart given by the classical FTP. In particular, this probability amplification underlies the supremacy of quantum computing. There are numerous statistical data from cognitive psychology, decision making, molecular biology, genetics and epigenetics demonstrating that biosystems, from proteins and cells (Asano et al., 2015b)<ref>Asano M., Khrennikov A., Ohya M., Tanaka Y., Yamato I. Quantum Adaptivity in Biology: From Genetics To Cognition Springer, Heidelberg-Berlin-New York(2015)</ref> to humans (Khrennikov, 2010,<ref>Khrennikov A. Ubiquitous Quantum Structure: From Psychology To Finances Springer, Berlin-Heidelberg-New York(2010)</ref> Busemeyer and Bruza, 2012<ref>Busemeyer J., Bruza P. Quantum Models of Cognition and Decision Cambridge Univ. Press, Cambridge(2012)</ref>) use this amplification and operate with non-CP updates.  
 
</blockquote>{{q2|With this somewhat courageous and risky preface we have highlighted the complexity of diagnostic processes and models especially in the presence of multifactorial pathologies such as Orofacial Pain and DTM that we will present in the next chapters}}{{Bib}}

Revision as of 10:53, 19 April 2023

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Masticationpedia
Article by  Gianni Frisardi

 

Introduction

As usual in the presentation of new sections of specific chapters, it is advisable to introduce recent and documented references on the subject which in this case is 'Orofacial Pain' and Temporomandibular Disorders. In this sense we can partially report a brief introduction by Martina Ferrillo et al.[1] on which we will make the first conceptual reflections reported by our thoughtful Linus before proceeding to the presentation of the clinical cases.

Question 2.jpg

The author points out that orofacial and neck pain comorbidities are often associated with TMD.[2] These coexisting conditions (particularly headaches, migraines, and neck pain) are not only highly associated with chronic pain-related TMDs, but also increase the risk of their development.[3][4][5] The International Classification of Headaches (ICHD)[6] and DC/TMD[7] consider the main characteristics of pain in headache and TMD, respectively. There are several hypotheses that attempt to explain the association between TMD and headache, including neuronal convergence, central sensitization, and inhibition of descending pain downregulatory mechanisms.[8][9] The close relationship between TMD, headache and neck pain has recently been evaluated, not only in terms of sharing common pathogenetic mechanisms and clinical features, but also considering that one condition might influence or promote the development of another.[10][4][11] These conditions can cause facial pain and are frequently associated with the development of craniofacial allodynia during painful exacerbation.[12] Indeed, pain in both conditions has been attributed to common dysfunctions of central pain regulation mechanisms..[13][14] On the other hand, the concomitant TMD and migraine showed worse levels of cutaneous hyperalgesia and allodynia, probably due to central and peripheral nervous system sensitization and impairment of descending pain modulatory pathways.[15][16]

Question 2.jpg

: The uncertainty of the measurement

All true and, among other things, the arguments are very engaging from an intellectual point of view, but we should take into account the series of assertions such as neuronal convergence, the inhibition of downregulation mechanisms of descending pain,[8][9] allodynia,[12] and the concept of measure that inevitably incorporates an uncertainty. We reported a very interesting study (Exploring electroencephalography with a model inspired by quantum mechanics) which demonstrated the existence of an error in the measurement of the EEG by defining a similar Heisenberg uncertainty principle called quasi-quantum model which led to a constant minimum value of uncertainty in the EEG measurement at and of . Note that the unit of is the result of sampling the EEG at 250 Hz and taking mass as the unit. This should make us reflect in interpreting the results of laboratory research because, as we will see in the presentation of subsequent clinical cases, the diagnostic error is around the corner. Enough error in the specific measurement of the neuronal district under examination to make a diagnosis of Orofacial Pain when instead there is a brain tumor that involved the same nervous district and simulates the symptoms of Orofacial Pain from Temporomandibular Disorders.

Therefore, objectivity, scientific humility and a change of mindset in the interpretation of biological phenomena are needed, a topic that we will address in the 'Extraordinary Science' section At this stage, however, it is advisable to sort out the contents by resuming the already anticipated references regarding the classification of Orofacial Pain and DTM but in a more specific way to address the clinical cases to follow. Temporomandibular disorders (TMD) are a group of musculoskeletal and neuromuscular conditions affecting the masticatory muscles, temporomandibular joint (TMJ) and other associated structures.[7] According to the diagnostic criteria for TMD (DC/TMD), as already reported, in 'Axis I', TMD could be divided into intra-articular disorders, including disc displacement, arthralgia, arthritis and osteoarthritis, and muscle disorders.[7] The latter are also referred to as “myogenic TMDs”, which can be further classified into: local myalgia, if the pain is localized on palpation; myofascial pain, if the pain spreads within the palpated muscle territory; and myofascial pain with referral, if the pain spreads beyond the border of the masticatory muscles.[7]

Question 2.jpg
Figure 1: Trasmissione efaptica

Machine language logic

With regard to "myogenic TMDs" it is not as simple as the description of the CDR appears because, as we have highlighted for our poor patient 'Mary Poppins', the muscle pain and bone deconstruction of the ATM had concealed, in a logic of classical language, a much more serious organic damage that beyond the classifications it was possible to resolve, after 10 years of pilgrimage among various specialists. Only by acquiring a machine language logic was it possible to interpret the encrypted code of the 'Ephaptic Transmission'. (Figure 1) Having said this, classifications are welcome but not the use of a verbal language logic which remains, however, a vague phenomenon and ambiguous. Formal language logics such as mathematics are certain in the sense that equation has no solutions in the set of real numbers, because in this set there are no numbers whose square is negative. The value is then defined, called the imaginary unit, which has the following property: The equation does not exist in mathematics as it does in medical diagnostics. Without going into overly specialized topics which, however, we will address in the 'Extraordinary Science' section, in a logic of verbal language the uncertainty is much higher than that which occurs in a logic of machine language because Poppins could be affected (as they are things went) from myalgia, TMD, vasculitis, Morphea or from hemimasticatory spasm while the 'Ephaptic transmission' remains forever an organic damage and the clinical interpretation cannot be dichotomous as cannot be but only .

A recent systematic review and meta-analysis, with a combined sample of 2518 subjects, suggested that the prevalence of TMD could range from 25.2% to 34.9%,[17] with a predominance of the myofascial pain diagnosis (10.3- 15.4%) [2]. While a study by Javed Ashraf et al.[18] using Bayesian methodology, aimed to examine the association of TMD-related pain with severe headaches (migraine and TTH) over an 11-year follow-up period compared with the frequency approach. Frequentist statistics suffer from some limitations, most notably the reliance on large sample sizes to accurately determine effect sizes.[19] Furthermore, contrary to the Frequentist methodology, Bayesian statistics do not provide a (fixed) result value but rather an interval containing the regression coefficient.[20] These intervals, called credible intervals (CI), place a probability on the best estimate among all possible values of the parameter estimates.[19]

Question 2.jpg

Quantum Probability

We agree with the considerations that emerged in the study by Buchinsky et al.[18] because perhaps or fortunately we will never be able to create a formal language logic such as mathematics given the intrinsic randomness of biological models. Even the Bayes models, however, incorporate a conceptual limit which, if exceeded, would improve the probabilistic data and contextually the predictive value in the output. Briefly, Bayes' formula looks like this:

It can therefore be noted that in order to calculate the predictive value of the test, it is also necessary to know the probability with which the disease affects the overall population . Therefore, a good test is a test with sensitivity and specificity very close to 0 and we all know that this is impossible and even wrong in some ways, however, it would be a paradigmatic test. The scarce added value, in terms of information, that tumor markers, for example, provide for diagnosis, represents the rationale for which their use as a screening test in an unselected population is not recommended. The same could happen for predictive values regarding TMD culminating in a massive classification of patients and an inevitable search for the truth by the RDC project.

Without going into specialized topics, we try to briefly describe the rationale for this statement by pointing out, mainly, the differences between a classical and a quantum probabilistic model. (for more but very specialized information, see 'Quantum-like modeling in biology with open quantum systems and instruments')

Therefore, in the closed probability (CP) the probability distribution can be computed from probability and conditional probabilities . In quantum probability (QP), the classical Total Probability Formula (FTP) is perturbed by the interference term (Khrennikov, 2010);[21] for the dichotomous quantum observables and of von Neumann type, i.e. given by the Hermitian operators and , the quantum version of FTP has the form:

If the interference term is positive, then the QP computation would generate a higher probability than its CP counterpart given by the classical FTP. In particular, this probability amplification underlies the supremacy of quantum computing. There are numerous statistical data from cognitive psychology, decision making, molecular biology, genetics and epigenetics demonstrating that biosystems, from proteins and cells (Asano et al., 2015b)[22] to humans (Khrennikov, 2010,[23] Busemeyer and Bruza, 2012[24]) use this amplification and operate with non-CP updates.

«With this somewhat courageous and risky preface we have highlighted the complexity of diagnostic processes and models especially in the presence of multifactorial pathologies such as Orofacial Pain and DTM that we will present in the next chapters»
Bibliography & references
  1. ↑ Martina Ferrillo, Amerigo Giudice, Nicola Marotta, Francesco Fortunato,Daniela Di Venere,Antonio Ammendolia, Pietro Fiore, and  Alessandro de Sire. Pain Management and Rehabilitation for Central Sensitization in Temporomandibular Disorders: A Comprehensive Review. Int J Mol Sci. 2022 Oct; 23(20): 12164. Published online 2022 Oct 12. doi: 10.3390/ijms232012164. PMCID: PMC9602546. PMID: 36293017
  2. ↑ Plesh O., Adams S.H., Gansky S.A. Temporomandibular joint and muscle disorder-type pain and comorbid pains in a national US sample. J. Orofac. Pain. 2011;25:190–198.
  3. ↑ Bender S.D. Orofacial pain and headache: A review and look at the commonalities. Curr Pain Headache Rep. 2014;18:400. doi: 10.1007/s11916-013-0400-5.
  4. ↑ 4.0 4.1 Botros J., Gornitsky M., Samim F., der Khatchadourian Z., Velly A.M. Back and neck pain: A comparison between acute and chronic pain-related Temporomandibular Disorders. Can. J. Pain. 2022;6:112–120. doi: 10.1080/24740527.2022.2067032.
  5. ↑ Ohrbach R., Fillingim R.B., Mulkey F., Gonzalez Y., Gordon S., Gremillion H., Lim P.-F., Ribeiro-Dasilva M., Greenspan J.D., Knott C. Clinical findings and pain symptoms as potential risk factors for chronic tmd: Descriptive data and empirically identified domains from the opera case-control study. J. Pain. 2011;12:T27–T45. doi: 10.1016/j.jpain.2011.09.001
  6. ↑ Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders; 3rd edition (beta version) Cephalalgia. 2013;33:629–808. doi: 10.1177/0333102413485658.
  7. ↑ 7.0 7.1 7.2 7.3 Schiffman E., Ohrbach R., Truelove E., Look J., Anderson G., Goulet J.P., List T., Svensson P., Gonzalez Y., Lobbezoo F., et al. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: Recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group† J. Oral Facial Pain Headache. 2014;28:6–27. doi: 10.11607/jop.1151
  8. ↑ 8.0 8.1 Matre D., Knardahl S. ‘Central sensitization’ in chronic neck/shoulder pain. Scand. J. Pain. 2012;3:230–235. doi: 10.1016/j.sjpain.2012.04.003.
  9. ↑ 9.0 9.1 Su M., Yu S. Chronic migraine: A process of dysmodulation and sensitization. Mol. Pain. 2018;14:1744806918767697. doi: 10.1177/1744806918767697.
  10. ↑ Chaves T.C., Dach F., Florencio L.L., Carvalho G.F., Gonçalves M.C., Bigal M.E., Speciali J.G., Bevilaqua-Grossi D. Concomitant Migraine and Temporomandibular Disorders are Associated With Higher Heat Pain Hyperalgesia and Cephalic Cutaneous Allodynia. Clin. J. Pain. 2016;32:882–888. doi: 10.1097/AJP.0000000000000369.
  11. ↑ Gonçalves D.A., Camparis C.M., Speciali J.G., Franco A.L., Castanharo S.M., Bigal M.E. Temporomandibular disorders are differentially associated with headache diagnoses: A controlled study. Clin. J. Pain. 2011;27:611–615. doi: 10.1097/AJP.0b013e31820e12f5.
  12. ↑ 12.0 12.1 Greenspan J.D., Slade G.D., Bair E., Dubner R., Fillingim R.B., Ohrbach R., Knott C., Diatchenko L., Liu Q., Maixner W. Pain sensitivity and autonomic factors associated with development of TMD: The OPPERA prospective cohort study. J. Pain. 2013;14:T63–T74.e746. doi: 10.1016/j.jpain.2013.06.007.
  13. ↑ Furquim B.D., Flamengui L.M., Conti P.C. TMD and chronic pain: A current view. Dental Press J. Orthod. 2015;20:127–133. doi: 10.1590/2176-9451.20.1.127-133.sar.
  14. ↑ Bevilaqua-Grossi D., Lipton R.B., Napchan U., Grosberg B., Ashina S., Bigal M.E. Temporomandibular disorders and cutaneous allodynia are associated in individuals with migraine. Cephalalgia. 2010;30:425–432. doi: 10.1111/j.1468-2982.2009.01928.x.
  15. ↑ Conti P.C., Costa Y.M., Gonçalves D.A., Svensson P. Headaches and myofascial temporomandibular disorders: Overlapping entities, separate managements? J. Oral Rehabil. 2016;43:702–715. doi: 10.1111/joor.12410.
  16. ↑ Furquim B.D., Flamengui L.M., Conti P.C. TMD and chronic pain: A current view. Dental Press J. Orthod. 2015;20:127–133. doi: 10.1590/2176-9451.20.1.127-133.sar.
  17. ↑ Bueno C.H., Pereira D.D., Pattussi M.P., Grossi P.K., Grossi M.L. Gender differences in temporomandibular disorders in adult populational studies: A systematic review and meta-analysis. J. Oral Rehabil. 2018;45:720–729. doi: 10.1111/joor.12661
  18. ↑ 18.0 18.1 Javed Ashraf,Matti Närhi, Anna Liisa Suominenand  Tuomas Saxlin. Association of temporomandibular disorder-related pain with severe headaches—a Bayesian view. Clin Oral Investig. 2022; 26(1): 729–738. Published online 2021 Jul 5. doi: 10.1007/s00784-021-04051-y. PMCID: PMC8791898. PMID: 34224000
  19. ↑ 19.0 19.1 Buchinsky FJ, Chadha NK. To P or not to P: backing Bayesian statistics. Otolaryngol Head Neck Surg. 2017;157(6):915–918. doi: 10.1177/0194599817739260
  20. ↑ Depaoli S, van de Schoot R. Bayesian analyses: where to start and what to report. Eur Heal Psychol. 2014;16:75–84.
  21. ↑ Khrennikov A. Ubiquitous Quantum Structure: From Psychology To Finances Springer, Berlin-Heidelberg-New York(2010)
  22. ↑ Asano M., Khrennikov A., Ohya M., Tanaka Y., Yamato I. Quantum Adaptivity in Biology: From Genetics To Cognition Springer, Heidelberg-Berlin-New York(2015)
  23. ↑ Khrennikov A. Ubiquitous Quantum Structure: From Psychology To Finances Springer, Berlin-Heidelberg-New York(2010)
  24. ↑ Busemeyer J., Bruza P. Quantum Models of Cognition and Decision Cambridge Univ. Press, Cambridge(2012)
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