Genetics of musculoskeletal (TMD) and neuropathic orofacial pain: a narrative review

Olga A. Korczeniewska; Divya Kohli; Kinga Dabek; Scott Diehl; Rafael Benoliel

doi:10.21037/fomm-22-12

Genetics of musculoskeletal (TMD) and neuropathic orofacial pain: a narrative review

Olga A. Korczeniewska, Divya Kohli, Kinga Dabek, Scott Diehl, Rafael Benoliel

Rutgers, The State University

Research output: Contribution to journal › Review article › peer-review

Abstract

Background and Objective: Orofacial pain is a debilitating condition affecting individuals’ quality of life. Differences in pain perception and analgesia have been reported between individuals, suggesting genetics as a contributing factor. This genetic component of orofacial pain can be best defined as complex due to contributions from multiple genes, which interact with each other and additional environmental factors. The objective of this review was to provide a summary of the progress made in the field of musculoskeletal [temporomandibular disorders (TMD)] and neuropathic orofacial pain genetics. Methods: PubMed database was searched using the following Medical Subject Headings: (("Facial Pain/genetics"[Mesh]) OR ("Trigeminal Neuralgia/genetics"[Mesh]) OR ("Trigeminal Nerve Diseases/ genetics"[Mesh]) OR (“Temporomandibular Joint Disorders/genetics"[Mesh])). The search was limited to publications in English. No time-frame restriction was used. Key Content and Findings: In this review, we discuss progress made in the field of orofacial pain genetics with the focus on non-malignant and non-odontogenic musculoskeletal, i.e., TMDs and forms of trigeminal neuropathic pain including post-traumatic trigeminal neuropathic pain (PTTN) and trigeminal neuralgia (TN). Available evidence supports the role of genetics in orofacial pain with variations in voltage gated ion channels, transient receptor potential channels, and GABA receptor-binding genes possessing the strongest support. Conclusions: For most cases, orofacial pain conditions such as TMDs, TN, and PTTN follow a complex multifactorial pattern of inheritance with multiple compounding environmental and genetic factors. Under such conditions, the effect of individual genetic variation is modest. Defining the implications of individual genetic factors would thus require large samples of hundreds or thousands of carefully diagnosed patients and well-matched controls to provide sufficient statistical power. Rare damaging mutations that have a major effect on risk probably account for a small portion of cases due to aggregation in families, but nonetheless may be valuable for identifying pathophysiological mechanisms. Overall, the current evidence strongly suggests that inherited genetic differences among individuals make an important contribution to the development and severity of pain in conditions such as TMDs, TN, and PTTN. Future research should be aimed at identifying both the common variants with modest effects and rare damaging mutations with large effects on increasing patient risk. Such findings would offer promising avenues for development of novel therapeutic approaches to improve treatment for patients suffering from these debilitating conditions.

Original language	American English
Article number	16
Journal	Frontiers of Oral and Maxillofacial Medicine
Volume	6
DOIs	https://doi.org/10.21037/fomm-22-12
State	Published - Jun 10 2024

ASJC Scopus subject areas

Surgery
Oral Surgery
Otorhinolaryngology

Keywords

Orofacial pain
genetic
oral pain
polymorphism

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10.21037/fomm-22-12

Cite this

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title = "Genetics of musculoskeletal (TMD) and neuropathic orofacial pain: a narrative review",

abstract = "Background and Objective: Orofacial pain is a debilitating condition affecting individuals{\textquoteright} quality of life. Differences in pain perception and analgesia have been reported between individuals, suggesting genetics as a contributing factor. This genetic component of orofacial pain can be best defined as complex due to contributions from multiple genes, which interact with each other and additional environmental factors. The objective of this review was to provide a summary of the progress made in the field of musculoskeletal [temporomandibular disorders (TMD)] and neuropathic orofacial pain genetics. Methods: PubMed database was searched using the following Medical Subject Headings: (({"}Facial Pain/genetics{"}[Mesh]) OR ({"}Trigeminal Neuralgia/genetics{"}[Mesh]) OR ({"}Trigeminal Nerve Diseases/ genetics{"}[Mesh]) OR (“Temporomandibular Joint Disorders/genetics{"}[Mesh])). The search was limited to publications in English. No time-frame restriction was used. Key Content and Findings: In this review, we discuss progress made in the field of orofacial pain genetics with the focus on non-malignant and non-odontogenic musculoskeletal, i.e., TMDs and forms of trigeminal neuropathic pain including post-traumatic trigeminal neuropathic pain (PTTN) and trigeminal neuralgia (TN). Available evidence supports the role of genetics in orofacial pain with variations in voltage gated ion channels, transient receptor potential channels, and GABA receptor-binding genes possessing the strongest support. Conclusions: For most cases, orofacial pain conditions such as TMDs, TN, and PTTN follow a complex multifactorial pattern of inheritance with multiple compounding environmental and genetic factors. Under such conditions, the effect of individual genetic variation is modest. Defining the implications of individual genetic factors would thus require large samples of hundreds or thousands of carefully diagnosed patients and well-matched controls to provide sufficient statistical power. Rare damaging mutations that have a major effect on risk probably account for a small portion of cases due to aggregation in families, but nonetheless may be valuable for identifying pathophysiological mechanisms. Overall, the current evidence strongly suggests that inherited genetic differences among individuals make an important contribution to the development and severity of pain in conditions such as TMDs, TN, and PTTN. Future research should be aimed at identifying both the common variants with modest effects and rare damaging mutations with large effects on increasing patient risk. Such findings would offer promising avenues for development of novel therapeutic approaches to improve treatment for patients suffering from these debilitating conditions.",

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AU - Korczeniewska, Olga A.

AU - Kohli, Divya

AU - Dabek, Kinga

AU - Diehl, Scott

AU - Benoliel, Rafael

PY - 2024/6/10

Y1 - 2024/6/10

N2 - Background and Objective: Orofacial pain is a debilitating condition affecting individuals’ quality of life. Differences in pain perception and analgesia have been reported between individuals, suggesting genetics as a contributing factor. This genetic component of orofacial pain can be best defined as complex due to contributions from multiple genes, which interact with each other and additional environmental factors. The objective of this review was to provide a summary of the progress made in the field of musculoskeletal [temporomandibular disorders (TMD)] and neuropathic orofacial pain genetics. Methods: PubMed database was searched using the following Medical Subject Headings: (("Facial Pain/genetics"[Mesh]) OR ("Trigeminal Neuralgia/genetics"[Mesh]) OR ("Trigeminal Nerve Diseases/ genetics"[Mesh]) OR (“Temporomandibular Joint Disorders/genetics"[Mesh])). The search was limited to publications in English. No time-frame restriction was used. Key Content and Findings: In this review, we discuss progress made in the field of orofacial pain genetics with the focus on non-malignant and non-odontogenic musculoskeletal, i.e., TMDs and forms of trigeminal neuropathic pain including post-traumatic trigeminal neuropathic pain (PTTN) and trigeminal neuralgia (TN). Available evidence supports the role of genetics in orofacial pain with variations in voltage gated ion channels, transient receptor potential channels, and GABA receptor-binding genes possessing the strongest support. Conclusions: For most cases, orofacial pain conditions such as TMDs, TN, and PTTN follow a complex multifactorial pattern of inheritance with multiple compounding environmental and genetic factors. Under such conditions, the effect of individual genetic variation is modest. Defining the implications of individual genetic factors would thus require large samples of hundreds or thousands of carefully diagnosed patients and well-matched controls to provide sufficient statistical power. Rare damaging mutations that have a major effect on risk probably account for a small portion of cases due to aggregation in families, but nonetheless may be valuable for identifying pathophysiological mechanisms. Overall, the current evidence strongly suggests that inherited genetic differences among individuals make an important contribution to the development and severity of pain in conditions such as TMDs, TN, and PTTN. Future research should be aimed at identifying both the common variants with modest effects and rare damaging mutations with large effects on increasing patient risk. Such findings would offer promising avenues for development of novel therapeutic approaches to improve treatment for patients suffering from these debilitating conditions.

AB - Background and Objective: Orofacial pain is a debilitating condition affecting individuals’ quality of life. Differences in pain perception and analgesia have been reported between individuals, suggesting genetics as a contributing factor. This genetic component of orofacial pain can be best defined as complex due to contributions from multiple genes, which interact with each other and additional environmental factors. The objective of this review was to provide a summary of the progress made in the field of musculoskeletal [temporomandibular disorders (TMD)] and neuropathic orofacial pain genetics. Methods: PubMed database was searched using the following Medical Subject Headings: (("Facial Pain/genetics"[Mesh]) OR ("Trigeminal Neuralgia/genetics"[Mesh]) OR ("Trigeminal Nerve Diseases/ genetics"[Mesh]) OR (“Temporomandibular Joint Disorders/genetics"[Mesh])). The search was limited to publications in English. No time-frame restriction was used. Key Content and Findings: In this review, we discuss progress made in the field of orofacial pain genetics with the focus on non-malignant and non-odontogenic musculoskeletal, i.e., TMDs and forms of trigeminal neuropathic pain including post-traumatic trigeminal neuropathic pain (PTTN) and trigeminal neuralgia (TN). Available evidence supports the role of genetics in orofacial pain with variations in voltage gated ion channels, transient receptor potential channels, and GABA receptor-binding genes possessing the strongest support. Conclusions: For most cases, orofacial pain conditions such as TMDs, TN, and PTTN follow a complex multifactorial pattern of inheritance with multiple compounding environmental and genetic factors. Under such conditions, the effect of individual genetic variation is modest. Defining the implications of individual genetic factors would thus require large samples of hundreds or thousands of carefully diagnosed patients and well-matched controls to provide sufficient statistical power. Rare damaging mutations that have a major effect on risk probably account for a small portion of cases due to aggregation in families, but nonetheless may be valuable for identifying pathophysiological mechanisms. Overall, the current evidence strongly suggests that inherited genetic differences among individuals make an important contribution to the development and severity of pain in conditions such as TMDs, TN, and PTTN. Future research should be aimed at identifying both the common variants with modest effects and rare damaging mutations with large effects on increasing patient risk. Such findings would offer promising avenues for development of novel therapeutic approaches to improve treatment for patients suffering from these debilitating conditions.

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Genetics of musculoskeletal (TMD) and neuropathic orofacial pain: a narrative review

Abstract

ASJC Scopus subject areas

Keywords

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