A novel rat model of temporomandibular disorder with improved face and construct validities

Phero, Anthony; Ferrari, Luiz F.; Taylor, Norman E.

doi:10.1016/j.lfs.2021.120023

Cited by 3 publications

(7 citation statements)

References 69 publications

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“…This model assesses chewing function as a surrogate for ongoing nociception in rats. 80 Specifically, the model measures the time taken for a rat to chew through an obstacle in a tube and has been shown to be sensitive to experimental arthritis of the temporomandibular joint. This model has been used to assess whether a COMT inhibitor (OR486,15 mg/ kg subcutaneously for 14 days) alters jaw function.…”

Section: Biogenic Amine Metabolism and Nociceptionmentioning

confidence: 99%

“…The effect of COMT inhibition has also been assessed in an animal model that may be more relevant to TMD. This model assesses chewing function as a surrogate for ongoing nociception in rats 80 . Specifically, the model measures the time taken for a rat to chew through an obstacle in a tube and has been shown to be sensitive to experimental arthritis of the temporomandibular joint.…”

Section: Pharmacological Evidencementioning

confidence: 99%

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The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

Cairns

2022

J of Oral Rehabilitation

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Background Temporomandibular disorders (TMD) are diagnosed based on symptom presentation and, like other functional pain disorders, often lack definitive pathology. There is a strong association between elevated stress levels and the severity of TMD‐related pain, which suggests that alterations in autonomic tone may contribute to this pain condition. Objectives This narrative review examines the association between altered autonomic function and pain in TMD. Methods Relevant articles were identified by searching PubMed and through the reference list of those studies. Results TMD sufferers report an increased incidence of orthostatic hypotension. As in other chronic musculoskeletal pain conditions, TMD is associated with increased sympathetic tone, diminished baroreceptor reflex sensitivity and decreased parasympathetic tone. It remains to be determined whether ongoing pain drives these autonomic changes and/or is exacerbated by them. To examine whether increased sympathetic tone contributes to TMD‐related pain through β2 adrenergic receptor activation, clinical trials with the beta blocker propranolol have been undertaken. Although evidence from small studies suggested propranolol reduced TMD‐related pain, a larger clinical trial did not find a significant effect of propranolol treatment. This is consistent with human experimental pain studies that were unable to demonstrate an effect of β2 adrenergic receptor activation or inhibition on masticatory muscle pain. In preclinical models of temporomandibular joint arthritis, β2 adrenergic receptor activation appears to contribute to inflammation and nociception, whereas in masticatory muscle, α1 adrenergic receptor activation has been found to induce mechanical sensitisation. Some agents used to treat TMD, such as botulinum neurotoxin A, antidepressants and α2 adrenergic receptor agonists, may interact with the autonomic nervous system as part of their analgesic mechanism. Conclusion Even if dysautonomia turns out to be a consequence rather than a causative factor of painful TMD, the study of its role has opened up a greater understanding of the pathogenesis of this condition.

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Section: Biogenic Amine Metabolism and Nociceptionmentioning

confidence: 99%

Section: Pharmacological Evidencementioning

confidence: 99%

The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

Cairns

2022

J of Oral Rehabilitation

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“…In response to the national discussion, there have been several rodent models developed recently with an eye to improving face validity (defined as the similarity in clinical signs and symptoms), construct validity (defined as similarity in pathophysiologic disease mechanisms), and predictive validity (defined as the relative effectiveness of various clinical interventions being mimicked by the model). Among these systems, models of complex regional pain syndrome (CPRS) ( 15 ), complex orthopedic trauma ( 16 ), temporomandibular joint pain ( 17 ), and a genetic model of widespread hyperalgesia ( 18 ) have been used effectively to determine pathophysiological mechanisms associated with these conditions.…”

Section: The Development Of Better Rodent Pain Modelsmentioning

confidence: 99%

Discovering chronic pain treatments: better animal models might help us get there

Taylor¹,

Ferrari²

2023

Journal of Clinical Investigation

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“…In an effort to create an assay that induces pTMD in manner that better emulates the multifactorial etiology of these conditions in humans, a study combining a pTMD predisposing factor—inflammation induced by the injection of carrageenan in the TMJ or sustained inhibition of the catechol- O -methyltransferase (COMT) enzyme, classically known for its role in chronic pain ( 160 – 162 ), including OFP ( 163 , 164 )—with a precipitating factor—jaw forced lengthening—found that the combination of COMT inhibition with jaw forced lengthening was able to extend the time rats needed to chew through obstacles—a proxy measure of OFP sensitivity—compared to exposure to each factor alone after 2 weeks ( 78 ). The assay's ability to produce longer lasting OFP remains to be demonstrated.…”

Section: Animal Assaysmentioning

confidence: 99%

“…The dolognawmeter has been used mainly to study OFP linked to oral cancer ( 282 – 284 ) and has thus far been under-used in the field of non-cancer OFP ( 285 ). A modified dolognawmeter to test rats (the ratgnawmeter) has also been developed ( 78 ).…”

Section: Orofacial Pain Measuresmentioning

confidence: 99%

Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go

et al. 2023

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Chronic primary orofacial pain (OFP) conditions such as painful temporomandibular disorders (pTMDs; i.e., myofascial pain and arthralgia), idiopathic trigeminal neuralgia (TN), and burning mouth syndrome (BMS) are seemingly idiopathic, but evidence support complex and multifactorial etiology and pathophysiology. Important fragments of this complex array of factors have been identified over the years largely with the help of preclinical studies. However, findings have yet to translate into better pain care for chronic OFP patients. The need to develop preclinical assays that better simulate the etiology, pathophysiology, and clinical symptoms of OFP patients and to assess OFP measures consistent with their clinical symptoms is a challenge that needs to be overcome to support this translation process. In this review, we describe rodent assays and OFP pain measures that can be used in support of chronic primary OFP research, in specific pTMDs, TN, and BMS. We discuss their suitability and limitations considering the current knowledge of the etiology and pathophysiology of these conditions and suggest possible future directions. Our goal is to foster the development of innovative animal models with greater translatability and potential to lead to better care for patients living with chronic primary OFP.

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A novel rat model of temporomandibular disorder with improved face and construct validities

Cited by 3 publications

References 69 publications

The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

Discovering chronic pain treatments: better animal models might help us get there

Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go

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