Difference between revisions of "7° Clinical case: Brainstem neoplasm in Orofacial pain"

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

</blockquote>{{ArtBy|autore=Gianni Frisardi}}

The brain stem is the caudal portion of the brain that connects the diencephalon to the spinal cord and cerebellum.<ref>Hurley RA, Flashman LA, Chow TW, Taber KH. The brainstem: anatomy, assessment, and clinical syndromes. J Neuropsychiatry Clin Neurosci. 2010;22(1):iv. doi: 10.1176/jnp.2010.22.1.iv. </ref> The brainstem mediates the sensory and motor pathways between the spinal cord and the brain and contains the nuclei of the cranial nerves, the ascending reticular activating system (ARAS), and the autonomic nuclei. It controls brainstem reflexes and the sleep-wake cycle and is responsible for autonomous control of the cardiovascular, respiratory, digestive and immune systems. Brainstem dysfunction can result from various acute or chronic insults, including stroke, infectious, cancer, inflammatory, and neurodegenerative diseases. In the context of critical illness, the brain stem can be susceptible to various insults that can be classified as structural and non-structural in origin. Brainstem dysfunction can therefore contribute to impaired consciousness, cardiocirculatory and respiratory insufficiency and therefore to increased mortality <ref>Annane D, Trabold F, Sharshar T, Jarrin I, Blanc AS, Raphael JC, et al. Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach. Am J Respir Crit Care Med août. 1999;160(2):458–465. doi: 10.1164/ajrccm.160.2.9810073.</ref><ref>Sharshar T, Porcher R, Siami S, Rohaut B, Bailly-Salin J, Hopkinson NS, et al. Brainstem responses can predict death and delirium in sedated patients in intensive care unit. Crit Care Med août. 2011;39(8):1960–1967. doi: 10.1097/CCM.0b013e31821b843b.</ref><ref>Sharshar T, Gray F, Lorin de la Grandmaison G, Hopkinson NS, Ross E, Dorandeu A, et al. Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet Lond Engl. 2003;362(9398):1799–1805. doi: 10.1016/S0140-6736(03)14899-4. </ref><ref>Mazeraud A, Pascal Q, Verdonk F, Heming N, Chrétien F, Sharshar T. Neuroanatomy and physiology of brain dysfunction in sepsis. Clin Chest Med. 2016;37(2):333–345. doi: 10.1016/j.ccm.2016.01.013.</ref> and especially manifest as orofacial pain (OP).[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945639/ Brainstem dysfunction in critically ill patients]:

<blockquote>These important premises extracted from an interesting article by Sarah Benghanem<ref>Benghanem S, Mazeraud A, Azabou E, Chhor V, Shinotsuka CR, Claassen J, Rohaut B, Sharshar T. Brainstem dysfunction in critically ill patients. Crit Care. 2020 Jan 6;24(1):5. doi: 10.1186/s13054-019-2718-9.PMID: 31907011</ref> are essential details, expression of a clinical experience which led the author of the chapter to scientific and epistemological reflections on the typology of language to be used in the creation of diagnostic models. and consequently to found Masticationpedia. One cannot, personal and responsible assertion of the author of the chapters, slavishly follow an axiom, a protocol such as the DRC or whatever and risk an error of differential diagnosis which can cost the life of a human being. If there is a gap in the model, which we will demonstrate during the implementation of Masticationpedia, then it should be noted as an anomaly, analyzed and eliminated or at least modified otherwise it is not a question of paradigmatic progress but only of intensive progress. </blockquote>

In the rare but real clinical cases in which the ' <math>\tau</math> Demarcator' is reset, we are motivated to carry out an even more extensive and in-depth check, hypothesizing serious pathologies <ref>Chloé Gibeili, Arek Sulukdjian, Audrey Chanlon, Nathan Moreau. Unilateral glossodynia as a harbinger of an occult cerebellopontine angle tumour. BMJ Case Report.. 2022 Apr 12;15(4):e249408.doi: 10.1136/bcr-2022-249408.

</ref> including head and neck tumors which simulate symptoms that can be superimposed on other pathologies. It is a serious mistake to consider the patient with such clinical manifestations and the simultaneous absence of systemic anomalies as a patient with psychosomatic disorders. Elements of psychophysical damage can certainly coexist but, if the 'Demarcator' fails, it is mandatory to deepen the diagnostics. In fact, head and neck cancer (HNC) affects over 890,000 people each year worldwide and has a 50% mortality rate. Aside from poor survival, HNC pain impairs eating, drinking and speaking, severely reducing quality of life. The different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between tumors<ref>'''Advances''' in '''Head''' and '''Neck''' '''Cancer''' '''Pain'''.

 

Ye Y, Jensen DD, Viet CT, Pan HL, Campana WM, Amit M, Boada MD.J Dent Res. 2022 Aug;101(9):1025-1033. doi: 10.1177/00220345221088527. Epub 2022 Apr 13.PMID: 35416080 </ref>. Glial and immune modulation of the tumor microenvironment, as well explained in the article by [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305840/ '''Ye et al.'''], influences not only cancer progression but also pain signaling among which transient receptor potentials contained in gustatory somatosensory systems are an example.<ref name=":0">Ramsey, I.S., M. Delling, and D.E. Clapham. 2006. An introduction to TRP channels. Annu Rev Physiol, 68: 619–647.</ref><ref name=":1">Julius, D. 2013. TRP channels and pain. Annu Rev Cell Dev Biol, 29: 355–584.</ref>

The mammalian gustatory system is made up of taste buds, which are clusters of 50-100 taste cells found throughout the oral cavity. On the tongue, which is the central topic of the case report 'Capsaicin', the taste buds are located on circumvallate, foliate and fungiform papillae. Taste cells synapse with afferent fibers from branches of the cranial facial (CN VII), glossopharyngeal (CN IX) and vagus (CN X) nerves which, in turn, transmit information to the central nervous system (CNS) about gustatory attributes , intensity and hedonic nature. <ref>Gutierrez, R., and S.A. Simon. 2011. Chemosensory processing in the taste-reward pathway. Flavour Fragr J, 26(4): 231–238.</ref><ref>Carleton, A., R. Accolla, and S.A. Simon. 2010. Coding in the mammalian gustatory system. Trends Neurosci, 33(7): 326–334.</ref><ref>Vincis, R. and A. Fontanini. 2016. A gustocentric perspective to understanding primary sensory cortices. Curr Opin Neurobiol, 40: 118–124</ref> The taste buds are embedded in a stratified squamous epithelium, which contains somatosensory branches of the trigeminal (CN V), glossopharyngeal (CN IX), and vagus (CN X) cranial nerves. Information from these general sensory nerves provides information to the central nervous system about mechanical, thermal, and pain stimuli.<ref name=":1" /><ref>Kaneko, Y., and A. Szallasi. 2014. Transient receptor potential (TRP) channels: A clinical perspective. Br J Pharmacol, 171(10): 2474–2507. </ref> Painful stimuli can result from strong or sharp mechanical stimuli, abnormally high or low temperatures, or chemical stimuli such as capsaicin, which is found in hot peppers and causes a burning taste sensation through the intervention of Transient Receptor Potentials (TRPs).<ref name=":0" /> These TRPs are divided into six subfamilies including TRPV1, which we are interested in to hypothesize the phenomenon of pain exacerbation of the patient 'Capsaicin' in spicy diet. [[File:Trpv1 pip2 bilayer.png|thumb|'''Figura 9:''' TRPV1, VR1, transient receptor potential cation channel subfamily V member 1. [[wikipedia:TRPV1|Wikipedia]]]]

TRPV1s constitute a distinct subset of non-selective cation channels (Transient Receptor Potential) responsible for many cellular responses. They are activated by various stimuli such as acids, extracellular protons, high temperatures, plant toxins and vanilloid agonists. The TRPV1s present in mammals can be considered as sensors of chemical substances (capsaicin), thermal substances (heat) and/or harmful stimuli. The activation of TRPV1 leads to the depolarization necessary for the propagation of action potentials along the axons of the dorsal root ganglia (DRG) of neurons that project to the spinal cord and consequently also to the nociceptive trigeminal nuclei. What makes TRPV1 so critical for pain signaling is undeniably its ability to transduce inflammatory signals into electrical signals with the activation of both voltage-gated sodium and calcium channels located at the nociceptor level.<ref>Bourinet E, Altier C, Hildebrand M E, Trang T, Salter MW, Zamponi GW. Calcium permeable ion channels in pain signaling. Physiol Rev 2014; 94: 81–140.</ref> The implication of TRPV1 in pathological pain prompted a careful study of these proteins. The limiting element in pharmacological research at the application level was the peculiarity of the TRPV1 channel, i.e. its polymodal mechanism of activation (heat, capsaicin, pH), which led to a high level of complexity in the design of a specific modality inhibitor.  

The interaction between neurons and immune cells is a well-known phenomenon.<ref>Jacobson A, Yang D, Vella M, Chiu IM (May 2021). "The intestinal neuro-immune axis: crosstalk between neurons, immune cells, and microbes". ''Mucosal Immunology''. '''14''' (3): 555–565. doi:10.1038/s41385-020-00368-1. PMC 8075967. <nowiki>PMID 33542493</nowiki>.</ref> TRPV1 plays its role, too, in neuroinflammation by being expressed in both neurons and immune cells. Significant importance should be given to the confirmed expression of TRPV1 in microglia and astrocytes, cells found in the vicinity of neurons. The neuro-immune axis is the site of production of neuroinflammatory molecules and receptors that interact between the two systems and ensure a complex response to external stimuli (or to the body's own pathologies). TRPV1 is said to contribute to microglia autophagy through its Ca²⁺ signaling, which leads to mitochondria-induced cell death. Basically, TRPV1 is a pro-apoptotic element.  

An interesting study by the Tominaga group extends the list of TRPV1 interactions also to [[wikipedia:ANO1|'''Anoctamin 1 (ANO 1)''']]  also known as Transmembrane member 16A (TMEM16A)<ref name=":2">Yasunori Takayama, Daisuke Uta, Hidemasa Furue, and Makoto Tominaga. Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons. Proc Natl Acad Sci 2015; 21; 112(16): 5213-5218. doi: 10.1073/pnas.1421507112. Epub 2015 Apr 6.</ref> a chloride channel which is usually activated by Ca2+. The authors demonstrate, in fact, that when TRPV1 interacts with the ANO1 channel it mediates the efflux of Chloride evoking depolarization (after stimulation by capsaicin) with increased excitability of the nociceptor. Tominaga<ref name=":2" /> highlighted a clear structural and functional crosstalk between TRPV1 and ANO1, which intervenes in the algogenic action of capsaicin.