Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Feb 16;17(2):e79098.
doi: 10.7759/cureus.79098. eCollection 2025 Feb.

Neuroplasticity and Pain Perception: Exploring the Complexities of Temporomandibular Disorders

Affiliations
Review

Neuroplasticity and Pain Perception: Exploring the Complexities of Temporomandibular Disorders

Pinaki Wani et al. Cureus. .

Abstract

Temporomandibular disorders (TMDs) are prevalent conditions affecting the temporomandibular joint (TMJ), masticatory muscles, and associated structures, leading to pain, restricted movement, and joint noises. These disorders are multifactorial in origin, involving structural, functional, and psychological components. This review delves into the neurophysiological mechanisms of pain perception in TMDs, focusing on peripheral and central processes, including the role of neural plasticity in chronic pain. Peripheral mechanisms involve nociceptors in the TMJ, activated by inflammatory mediators, mechanical stress, and tissue damage, leading to pain. Peripheral sensitization, driven by factors such as cytokines and neuropeptides, enhances nociceptor sensitivity, contributing to chronic pain states. The trigeminal nerve is pivotal in transmitting nociceptive information to the central nervous system (CNS), with C-fibers and A-delta fibers involved in pain perception. Central sensitization, a hallmark of chronic pain in TMDs, involves neuroplastic changes in the CNS, including wind-up and long-term potentiation (LTP), enhancing pain perception and facilitating pain persistence. Neuroplasticity, both central and peripheral, plays a critical role in the development of chronic pain. Central plasticity includes synaptic changes and alterations in brain connectivity, which were observed in functional imaging studies of TMD patients. Peripheral plasticity involves the upregulation of ion channels and neurotransmitters, sustaining pain signals. Additionally, neuroimmune interactions between microglia, astrocytes, and pain pathways are integral to central sensitization. Understanding these mechanisms is crucial for developing effective treatments targeting both peripheral and central pain processes. Emerging therapies, including transient receptor potential (TRP) channel blockers and neuroimmune modulators, offer new avenues for managing TMD pain, emphasizing the need for a multifaceted treatment approach.

Keywords: central sensitization; chronic pain; neuroimmune interactions; neuroplasticity; pain perception; peripheral sensitization; temporomandibular disorders; trigeminal nerve.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Similar articles

Cited by

References

    1. Research diagnostic criteria for temporomandibular disorders: a systematic review of axis I epidemiologic findings. Manfredini D, Guarda-Nardini L, Winocur E, Piccotti F, Ahlberg J, Lobbezoo F. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112:453–462. - PubMed
    1. Epidemiology of temporomandibular disorders: implications for the investigation of etiologic factors. LeResche L. Crit Rev Oral Biol Med. 1997;8:291–305. - PubMed
    1. Peripheral and central mechanisms of orofacial pain and their clinical correlates. Sessle BJ. https://pubmed.ncbi.nlm.nih.gov/15756153/ Minerva Anestesiol. 2005;71:117–136. - PubMed
    1. Central sensitization: implications for the diagnosis and treatment of pain. Woolf CJ. https://pubmed.ncbi.nlm.nih.gov/20961685/ Pain. 2011;152:0. - PMC - PubMed
    1. The role of inflammatory markers in temporomandibular myalgia: a systematic review. Farré-Guasch E, Aliberas JT, Spada NF, de Vries R, Schulten EA, Lobbezoo F. Jpn Dent Sci Rev. 2023;59:281–288. - PMC - PubMed

LinkOut - more resources