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Reflectory trismus and initiation of fibrosis from an early mucosal inflammation in oral submucous fibrosis
Oral Oncology 51 (2015) e17–e18
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the editor Reflectory trismus and initiation of fibrosis from an early mucosal inflammation in oral submucous fibrosis
Restricted mouth opening (RMO) in Oral Submucous Fibrosis (OSMF) has always been attributed to the progressive fibrotic change in the oral cavity [1]. The inflammation in the context of OSMF is contributory to its pathogenesis, and is one of the important pathways in the proposed etiology [1,2]. Betel quid chewing has been a major etiology in the disease process in the OSMF; which contains arecanut, slaked lime, betel leaves and tobacco [3]. The arecanut, a class I carcinogen is known to cause various diseases including OSMF and oral cancer; arecanut contains, alkaloids (arecoline, arecaidine, guvacine, and guvacoline) which lead to increase in collagen deposition and flavinoids (tannins and catechins) lead to cause decrease in collagen degradation [3,4]. The inflammation in the oral cavity sets in due to over usage of the betel quid chewing habit, external trauma from the quid and various irritants in the quid, like slaked lime and their metabolites; thus the inflammation in OSMF could be considered as an initial process [5]. TGF-b is a key regulator of fibrotic change in OSMF disease process; and the inflammatory pathways in OSMF are also mediated by the TGF-b [5–7]. As suggested by Rajalalitha and Vali, TGF-b favors the collagen production by activation of procollagen genes, elevation of procollagen proteinases levels, and up-regulation of lysyl oxidase (LOX) activity. The inflammation thus could be an important component in the fibrotic change and RMO in OSMF [5]. Inflammation is one of the events in the oral submucous fibrosis which occurs as a series of steps; thought to arise due to effect of betel quid which contains slaked lime, catechu and arecanut [6,7]. The alkaloids and the flavinoids content in the arecanut are prominent reasons for the inflammation and progressive fibrotic change in oral submucous fibrosis [5–7]. The frequency of multinucleated cells assessment in betel quid chewers showed a significant score and also showed significantly elevated frequencies of exfoliated human oral mucosal cells [8]. In addition to this, Nair et al. also have reported chromosome breaks in chewers with or without tobacco. Sister chromatid exchange and chromosome aberrations were determined in peripheral blood lymphocytes of betel quid chewers [8–10]. During chewing of betel quid, reactive oxygen species (ROS) responsible for carcinogenesis are produced in the oral cavity; the production is also activated and enhanced by the Fe 2+, Fe 3+ and Cu 2+ [9]. Thus early inflammation due to betel quid chewing could lead to the initiating factor for disease process in OSMF, and the inflammatory component naturally could contributes to the fibrotic change. The fibrosis initiated from this early inflammation could add to the theoretical basis for the fibrosis in OSMF.
http://dx.doi.org/10.1016/j.oraloncology.2014.10.013 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
According to the concept of Reflectory trismus, reflexes causing the RMO are present in and around the areas of the oral cavity; sensory fibers from these areas ascends through the second and third division of the trigeminal nerve and glossopharyngeal nerve [11,12]. And according to Kveton and Pillsbury, principal sensory trigeminal nucleus in the pons is responsible for the RMO [13,14]. The reflexes from the triggering zones are conducted partly central to the sensory cortex, where they are registered as pain, and partly to the motor nucleus of the trigeminal nerve. In this way, the efferent part of the tonic reflex arch of the muscles of mastication is activated. The result is an increased tonus which develops as RMO [11,12]. Hence, the early oral mucosal inflammation in OSMF could trigger the RMO reflexes (Fig. 1). We would like to suggest through this letter that, RMO could also develop from the early mucosal inflammation in OSMF and the early inflammation could be an initiating factor for fibrosis. Now there is conclusive evidence of the Betel quid chewing as the major risk factor in OSMF, but the exact mechanism is not clearly understood to elucidate it. Hence, RMO in OSMF may be an earlier characteristic derived from the initial mucosal inflammation; and the mucosal inflammation in a tobacco chewer may depend on the biology of the patient whether it would progress to fibrosis or OSMF. Research has to focus whether the fibrosis solely would depend on the inflammation or the fibrosis begins without the inflammation. Studying the OSMF for Reflectory Trismus would elude the preconceptions and would easily clarify the reflexes causing RMO, how they are interpreted centrally, how they take part in inflammation of the oral cavity and what are the triggering zones in RMO. Conflict of interest statement There is no conflict of interest. References [1] Murti PR, Bhonsle RB, Gupta PC, Daftary DK, Pindborg JJ, Mehta FS. Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing. J Oral Pathol Med 1995;24(4):145–52. [2] Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S. Oral submucous fibrosis: review on aetiology and pathogenesis. Oral Oncol 2006;42(6):561–8. [3] Zain RB, Ikeda N, Gupta PC, Warnakulasuriya S, van Wyk CW, Shrestha P, et al. Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25–27, 1996. J Oral Pathol Med 1999;28(1):1–4. [4] IARC. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum 2004;83:1–1438. [5] Rajalalitha P, Vali S. Molecular pathogenesis of oral submucous fibrosis–a collagen metabolic disorder. J Oral Pathol Med 2005;34(6):321–8. [6] Nair UJ, Nair J, Friesen MD, Bartsch H, Ohshima H. Ortho- and meta-tyrosine formation from phenylalanine in human saliva as a marker of hydroxyl radical generation during betel quid chewing. Carcinogenesis 1995;16950:1195–8.
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Letter to the editor / Oral Oncology 51 (2015) e17–e18
Fig. 1. Reflectory trismus in OSMF, showing early mucosal inflammation which could lead to RMO and an initiating factor for fibrosis.
[7] Feller L, Altini M, Lemmer J. Inflammation in the context of oral cancer. Oral Oncol 2013 Sep;49(9):887–92. [8] Nair U, Obe G, Nair J, Maru GB, Bhide SV, Pieper R, et al. Evaluation of frequency of micronucleated oral mucosa cells as a marker for genotoxic damage in chewers of betel quid with or without tobacco. Mutat Res 1991;261(3):163–8. [9] Nair U, Bartsch H, Nair J. Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms. Mutagenesis 2004;19(4):251–62. [10] Dave BJ, Trivedi AH, Adhvaryu SG. Cytogenetic studies reveal increased genomic damage among ‘pan masala’ consumers. Mutagenesis 1991;6(2): 159–63. [11] Satheeshkumar PS, Mohan MP. Reflectory trismus in head and neck cancer. Oral Oncol 2013;49(8):e23–4. [12] Satheeshkumar PS, Mohan MP. Jacob J Restricted mouth opening and trismus in oral oncology. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117(6):709–15. [13] Kveton JF, Pillsbury HC. ‘‘How I do it’’–head and neck. A targeted problem and its solution. Breaking trismus to facilitate drainage of peritonsillar abscess. Laryngoscope 1980;90(11 Pt 1):1892–3.
[14] Kilty SJ, Gaboury I. Clinical predictors of peritonsillar abscess in adults. J Otolaryngol Head Neck Surg 2008;37(2):165–8.
P.S. Satheeshkumar Minu P. Mohan Mar Baselios Dental College, Department of Oral Medicine and Radiology, Thankalam, Kothamangalam, Ernakulam, Kerala 686 691, India Tel.: +91 9946321804 (P.S. Satheeshkumar). E-mail addresses: [email protected] (P.S. Satheeshkumar), [email protected] (M.P. Mohan) Available online 6 November 2014
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Letter to the editor Reflectory trismus and initiation of fibrosis from an early mucosal inflammation in oral submucous fibrosis
Restricted mouth opening (RMO) in Oral Submucous Fibrosis (OSMF) has always been attributed to the progressive fibrotic change in the oral cavity [1]. The inflammation in the context of OSMF is contributory to its pathogenesis, and is one of the important pathways in the proposed etiology [1,2]. Betel quid chewing has been a major etiology in the disease process in the OSMF; which contains arecanut, slaked lime, betel leaves and tobacco [3]. The arecanut, a class I carcinogen is known to cause various diseases including OSMF and oral cancer; arecanut contains, alkaloids (arecoline, arecaidine, guvacine, and guvacoline) which lead to increase in collagen deposition and flavinoids (tannins and catechins) lead to cause decrease in collagen degradation [3,4]. The inflammation in the oral cavity sets in due to over usage of the betel quid chewing habit, external trauma from the quid and various irritants in the quid, like slaked lime and their metabolites; thus the inflammation in OSMF could be considered as an initial process [5]. TGF-b is a key regulator of fibrotic change in OSMF disease process; and the inflammatory pathways in OSMF are also mediated by the TGF-b [5–7]. As suggested by Rajalalitha and Vali, TGF-b favors the collagen production by activation of procollagen genes, elevation of procollagen proteinases levels, and up-regulation of lysyl oxidase (LOX) activity. The inflammation thus could be an important component in the fibrotic change and RMO in OSMF [5]. Inflammation is one of the events in the oral submucous fibrosis which occurs as a series of steps; thought to arise due to effect of betel quid which contains slaked lime, catechu and arecanut [6,7]. The alkaloids and the flavinoids content in the arecanut are prominent reasons for the inflammation and progressive fibrotic change in oral submucous fibrosis [5–7]. The frequency of multinucleated cells assessment in betel quid chewers showed a significant score and also showed significantly elevated frequencies of exfoliated human oral mucosal cells [8]. In addition to this, Nair et al. also have reported chromosome breaks in chewers with or without tobacco. Sister chromatid exchange and chromosome aberrations were determined in peripheral blood lymphocytes of betel quid chewers [8–10]. During chewing of betel quid, reactive oxygen species (ROS) responsible for carcinogenesis are produced in the oral cavity; the production is also activated and enhanced by the Fe 2+, Fe 3+ and Cu 2+ [9]. Thus early inflammation due to betel quid chewing could lead to the initiating factor for disease process in OSMF, and the inflammatory component naturally could contributes to the fibrotic change. The fibrosis initiated from this early inflammation could add to the theoretical basis for the fibrosis in OSMF.
http://dx.doi.org/10.1016/j.oraloncology.2014.10.013 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
According to the concept of Reflectory trismus, reflexes causing the RMO are present in and around the areas of the oral cavity; sensory fibers from these areas ascends through the second and third division of the trigeminal nerve and glossopharyngeal nerve [11,12]. And according to Kveton and Pillsbury, principal sensory trigeminal nucleus in the pons is responsible for the RMO [13,14]. The reflexes from the triggering zones are conducted partly central to the sensory cortex, where they are registered as pain, and partly to the motor nucleus of the trigeminal nerve. In this way, the efferent part of the tonic reflex arch of the muscles of mastication is activated. The result is an increased tonus which develops as RMO [11,12]. Hence, the early oral mucosal inflammation in OSMF could trigger the RMO reflexes (Fig. 1). We would like to suggest through this letter that, RMO could also develop from the early mucosal inflammation in OSMF and the early inflammation could be an initiating factor for fibrosis. Now there is conclusive evidence of the Betel quid chewing as the major risk factor in OSMF, but the exact mechanism is not clearly understood to elucidate it. Hence, RMO in OSMF may be an earlier characteristic derived from the initial mucosal inflammation; and the mucosal inflammation in a tobacco chewer may depend on the biology of the patient whether it would progress to fibrosis or OSMF. Research has to focus whether the fibrosis solely would depend on the inflammation or the fibrosis begins without the inflammation. Studying the OSMF for Reflectory Trismus would elude the preconceptions and would easily clarify the reflexes causing RMO, how they are interpreted centrally, how they take part in inflammation of the oral cavity and what are the triggering zones in RMO. Conflict of interest statement There is no conflict of interest. References [1] Murti PR, Bhonsle RB, Gupta PC, Daftary DK, Pindborg JJ, Mehta FS. Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing. J Oral Pathol Med 1995;24(4):145–52. [2] Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S. Oral submucous fibrosis: review on aetiology and pathogenesis. Oral Oncol 2006;42(6):561–8. [3] Zain RB, Ikeda N, Gupta PC, Warnakulasuriya S, van Wyk CW, Shrestha P, et al. Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25–27, 1996. J Oral Pathol Med 1999;28(1):1–4. [4] IARC. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum 2004;83:1–1438. [5] Rajalalitha P, Vali S. Molecular pathogenesis of oral submucous fibrosis–a collagen metabolic disorder. J Oral Pathol Med 2005;34(6):321–8. [6] Nair UJ, Nair J, Friesen MD, Bartsch H, Ohshima H. Ortho- and meta-tyrosine formation from phenylalanine in human saliva as a marker of hydroxyl radical generation during betel quid chewing. Carcinogenesis 1995;16950:1195–8.
e18
Letter to the editor / Oral Oncology 51 (2015) e17–e18
Fig. 1. Reflectory trismus in OSMF, showing early mucosal inflammation which could lead to RMO and an initiating factor for fibrosis.
[7] Feller L, Altini M, Lemmer J. Inflammation in the context of oral cancer. Oral Oncol 2013 Sep;49(9):887–92. [8] Nair U, Obe G, Nair J, Maru GB, Bhide SV, Pieper R, et al. Evaluation of frequency of micronucleated oral mucosa cells as a marker for genotoxic damage in chewers of betel quid with or without tobacco. Mutat Res 1991;261(3):163–8. [9] Nair U, Bartsch H, Nair J. Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms. Mutagenesis 2004;19(4):251–62. [10] Dave BJ, Trivedi AH, Adhvaryu SG. Cytogenetic studies reveal increased genomic damage among ‘pan masala’ consumers. Mutagenesis 1991;6(2): 159–63. [11] Satheeshkumar PS, Mohan MP. Reflectory trismus in head and neck cancer. Oral Oncol 2013;49(8):e23–4. [12] Satheeshkumar PS, Mohan MP. Jacob J Restricted mouth opening and trismus in oral oncology. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117(6):709–15. [13] Kveton JF, Pillsbury HC. ‘‘How I do it’’–head and neck. A targeted problem and its solution. Breaking trismus to facilitate drainage of peritonsillar abscess. Laryngoscope 1980;90(11 Pt 1):1892–3.
[14] Kilty SJ, Gaboury I. Clinical predictors of peritonsillar abscess in adults. J Otolaryngol Head Neck Surg 2008;37(2):165–8.
P.S. Satheeshkumar Minu P. Mohan Mar Baselios Dental College, Department of Oral Medicine and Radiology, Thankalam, Kothamangalam, Ernakulam, Kerala 686 691, India Tel.: +91 9946321804 (P.S. Satheeshkumar). E-mail addresses: [email protected] (P.S. Satheeshkumar), [email protected] (M.P. Mohan) Available online 6 November 2014