Mechanisms Behind Oral Cancer Pain

Overseen By Caroline Sawicki, DDS, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU College of Dentistry

Disqualifiers: Prior head and neck cancer treatment, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

80 Participants Needed

Trial Summary

What is the purpose of this trial?

Oral squamous cell carcinoma (SCC) produces a higher prevalence and more severe pain than all other cancers. Orofacial pain is one of the most common initial symptoms of oral cancer and often leads to the diagnosis of oral cancer. However, the character, severity, and unique features of oral cancer widely differ between patients. There is currently no effective and lasting treatment available to alleviate suffering from oral cancer pain. A significant obstacle to effectively treating cancer pain is that the relative contributions of nociceptive mediators and their mechanisms of action (i.e., responsible receptors) are largely unknown. There is, therefore, a critical need to define the neurobiologic mechanisms responsible for oral cancer pain. Without such information, the promise of non-opioid therapy for the treatment of oral cancer pain will remain unfulfilled. The primary objective of this study is to define and quantify the phenotype of oral cancer pain in patients, by comparing mechano- and chemosensitivity in oral cancer patients with healthy subjects. Pain will be stimulated on the site of cancer in 40 oral cancer patients and on the tongue in 40 healthy volunteers utilizing chemical sensitivity and mechanical sensitivity tests.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the idea that Mechanisms Behind Oral Cancer Pain (also known as: Pain Stimulation Tests) is an effective treatment?

The available research does not provide direct evidence that Mechanisms Behind Oral Cancer Pain is an effective treatment. Instead, it highlights the complexity and intensity of pain experienced by oral cancer patients, which is often resistant to current pain medications like opioids. The studies focus on understanding the pain characteristics and potential factors influencing it, such as alcohol consumption, rather than evaluating the effectiveness of this specific treatment. Therefore, there is no data supporting its effectiveness compared to other treatments. ^{1 2 3 4 5}

What safety data exists for the treatment in the oral cancer pain trial?

The provided research does not directly address safety data for the treatment or Pain Stimulation Tests. The studies focus on characterizing pain mechanisms, evaluating pain levels, and exploring molecular mediators in oral cancer pain, but do not provide specific safety data for the treatment being evaluated in the clinical trial. ^{1 2 6 7 8}

Is the treatment Pain Stimulation Tests a promising treatment for oral cancer pain?

Pain Stimulation Tests could be promising for oral cancer pain because they help understand how oral cancer affects nerves and causes pain. This understanding can lead to new ways to manage pain, which is often severe and hard to treat with current methods. ^{1 6 9 10 11}

Eligibility Criteria

This trial is for individuals in good health with a confirmed diagnosis of oral squamous cell carcinoma that's at least 1 cm wide and requires surgery. It's not open to those who are pregnant, breastfeeding, or have had previous treatments for head and neck cancer.

Inclusion Criteria

The area of concern is at least 1 cm in size.

I have a confirmed diagnosis of squamous cell carcinoma in my mouth that needs surgery.

In good general health as evidenced by medical history

Exclusion Criteria

Pregnancy or lactation

I have had surgery, chemotherapy, or radiation for head and neck cancer.

I have been diagnosed with oral pre-cancer or cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Mechanical and chemical sensitivity tests are conducted on oral cancer patients and healthy subjects

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after baseline assessments

4 weeks

Treatment Details

Interventions

• Pain Stimulation Tests

Trial Overview The study aims to understand the unique pain associated with oral cancer by comparing sensitivity to pain in patients versus healthy volunteers using tests that measure response to mechanical pressure and chemical stimuli on affected areas.

Who Is Running the Clinical Trial?

NYU College of Dentistry

Lead Sponsor

Trials

12

Recruited

12,300+

Findings from Research

Oral squamous cell carcinoma (OSCC) activates pain-sensing channels (TRPA1 and TRPV1) that contribute to thermal allodynia, indicating a specific molecular mechanism behind the pain experienced by oral cancer patients.

Regular alcohol consumption in patients correlates with lower pain scores across various types of pain, suggesting that alcohol may have a pain-relieving effect, potentially delaying the urgency for medical care and impacting early detection of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Cancer Pain Includes Thermal Allodynia That May Be Attenuated by Chronic Alcohol Consumption. Gonzales, CB., De La Chapa, JJ., Patwardhan, AM., et al.[2023]

A novel pain questionnaire developed for patients with oral squamous cell carcinoma revealed that 14 out of 15 patients experienced functional restrictions due to pain, with an average pain intensity score of 46.6 on a scale of 0 to 100.

The study found that men reported significantly higher levels of function-related pain intensity and sharpness compared to women, and there was a strong correlation between the presence of nodal disease and increased spontaneous pain intensity and overall functional restriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pain in patients with oral squamous cell carcinoma. Connelly, ST., Schmidt, BL.[2015]

A pilot study involving 25 head and neck cancer patients developed a detailed pain assessment questionnaire, revealing that 88% of patients reported pain at the tumor site, with many experiencing neuropathic pain symptoms like 'burning' and 'pins and needles'.

The study found that advanced tumor staging significantly increases pain sensitivity, particularly to hot or spicy foods and hard textures, highlighting the need for personalized pain management strategies based on individual pain profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study to improve pain phenotyping in head and neck cancer patients. Ye, Y., Cardoso, DM., Kayahara, GM., et al.[2023]

In a review of 1412 oral cancer patients, 19.2% reported pain as their initial symptom, with a higher prevalence in men, indicating that pain can be an important early warning sign of oral cancer.

The study identified 12 types of pain complaints, with sore throat being the most common, and found that pain was associated with more advanced cancer stages, particularly in tumors located in the tongue and mouth floor, suggesting the need for thorough evaluations in patients presenting with orofacial pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain complaint as the first symptom of oral cancer: a descriptive study. Cuffari, L., Tesseroli de Siqueira, JT., Nemr, K., et al.[2022]

In a pilot study of 24 patients with early-stage oral squamous cell carcinoma (OSCC) of the tongue, 13 reported pain, suggesting a notable prevalence of pain in this condition.

The study found that painful tumors (P+ group) were associated with more intense lymphoplasmocytic inflammation compared to non-painful tumors (P- group), indicating a potential link between pain and inflammatory response in OSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency of pain and correlation with clinical and histologic parameters in T1 squamous cell carcinoma of the tongue: a retrospective pilot study. Nikitakis, NG., Sarlani, E., Kolokythas, A., et al.[2018]

In two mouse models of oral cancer, researchers found that pain associated with oral squamous cell carcinoma (oSCC) was linked to changes in immune cell infiltration, but this pain did not depend on inflammation, as shown by experiments with immune-deficient mice.

The study identified tumor necrosis factor alpha (TNFα) as a key mediator in oral cancer pain, as inhibiting its signaling reduced pain responses and affected T-cell infiltration, suggesting that targeting TNFα could be a potential strategy for managing pain in oral cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor necrosis factor alpha secreted from oral squamous cell carcinoma contributes to cancer pain and associated inflammation. Scheff, NN., Ye, Y., Bhattacharya, A., et al.[2022]

In rat models of orofacial cancer, the anti-inflammatory drug indomethacin effectively reduced pain symptoms, but the effect was weaker compared to its impact on inflammation-induced pain, indicating a different underlying mechanism for cancer-related pain.

Neurochemical analysis showed that pain in the inflammation model was associated with increased levels of pain-related substances, while these levels did not change in the cancer model, suggesting that cancer-induced pain may not be primarily driven by inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences between orofacial inflammation and cancer pain. Harano, N., Ono, K., Hidaka, K., et al.[2018]

A new operant system was developed to effectively measure orofacial pain sensitivity in response to both mechanical and thermal stimuli.

This system can detect both pain and analgesic responses, allowing for consistent comparison of different types of pain stimuli using the same outcome measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptation of a novel operant orofacial testing system to characterize both mechanical and thermal pain. Nolan, TA., Hester, J., Bokrand-Donatelli, Y., et al.[2021]

In a murine model of oral squamous cell carcinoma (OSCC), tumors on the tongue were found to increase spontaneous firing in sensory nerve fibers, leading to heightened pain sensitivity and altered sensations.

The study revealed that while certain mechanoreceptor fibers became more sensitive due to the tumor, others remained unaffected, highlighting specific changes in nerve response that could help understand pain mechanisms in oral cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depiction of Oral Tumor-Induced Trigeminal Afferent Responses Using Single-Fiber Electrophysiology. Grayson, M., Furr, A., Ruparel, S.[2021]

Quantitative Sensory Testing (QST) is a reliable method for assessing sensory function in the facial area, providing valuable insights into various orofacial pain conditions, including neuropathic pain and central sensitization.

Standardized QST parameters can enhance our understanding of the underlying mechanisms of orofacial pain, potentially leading to improved therapeutic strategies and the development of specific clinical screenings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Quantitative Sensory Testing in the facial area: a review]. Eberhard, L.[2013]

A new rat model of oral cancer pain was established by inoculating squamous cell carcinoma cells into the lower gingiva, leading to significant pain responses such as mechanical allodynia and thermal hyperalgesia.

The study found increased levels of pain-related molecules (CGRP, substance P, P2X(3), and TRPV1) in the trigeminal ganglia, suggesting these may play a key role in the pain mechanisms associated with oral cancer, which could help in developing new pain relief strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats. Nagamine, K., Ozaki, N., Shinoda, M., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Oral Cancer Pain Includes Thermal Allodynia That May Be Attenuated by Chronic Alcohol Consumption. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Evaluation of pain in patients with oral squamous cell carcinoma. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A pilot study to improve pain phenotyping in head and neck cancer patients. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Pain complaint as the first symptom of oral cancer: a descriptive study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Frequency of pain and correlation with clinical and histologic parameters in T1 squamous cell carcinoma of the tongue: a retrospective pilot study. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Tumor necrosis factor alpha secreted from oral squamous cell carcinoma contributes to cancer pain and associated inflammation. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Differences between orofacial inflammation and cancer pain. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Adaptation of a novel operant orofacial testing system to characterize both mechanical and thermal pain. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Depiction of Oral Tumor-Induced Trigeminal Afferent Responses Using Single-Fiber Electrophysiology. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

[Quantitative Sensory Testing in the facial area: a review]. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats. [2022]