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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to learn more about the pain caused by oral cancer, specifically oral squamous cell carcinoma. Researchers seek to understand why this type of cancer causes such severe pain and how it affects patients differently. The study will involve Pain Stimulation Tests to assess pain responses in 40 patients with oral cancer and compare them to 40 healthy individuals. Those diagnosed with oral squamous cell carcinoma who need surgery and have a cancer lesion of at least 1 cm in size may be suitable for the trial. Understanding these pain mechanisms could aid in developing better, non-opioid treatments for oral cancer pain. As an unphased trial, this study offers patients a chance to contribute to groundbreaking research that could lead to improved pain management strategies.

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 prior data suggests that these pain stimulation tests are safe?

Research has shown that tests used to study oral cancer pain, such as pain stimulation tests, are generally safe. For instance, a study on a similar method called cutaneous neuromodulation found it safely reduced cancer pain by stimulating the skin to affect nerves.

These tests aim to better understand pain, and most participants handle them well without serious side effects. It is important to note that this study does not involve new drugs or treatments but focuses on understanding pain mechanisms. This approach presents a lower risk compared to trials that test new medications. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Pain Stimulation Tests because they offer a new way to understand oral cancer pain that goes beyond simply treating symptoms. Unlike current pain management options, which often rely on medications like opioids to temporarily relieve pain, these tests aim to uncover the underlying mechanisms that cause pain in oral cancer patients. By pinpointing the root causes, scientists hope to develop more targeted and effective treatments in the future, potentially reducing the need for drugs that come with significant side effects. This approach could lead to breakthroughs in how we manage and alleviate oral cancer pain.

What evidence suggests that these pain stimulation tests are effective for understanding oral cancer pain?

Research has shown that oral squamous cell carcinoma, a type of mouth cancer, often causes more pain than other cancers. This pain varies among individuals and is difficult to treat. Current studies, including this trial, aim to better understand this pain by testing patient reactions to various pain triggers, such as physical touch or chemicals. Although these tests do not directly reduce pain, they help researchers identify potential causes, which could lead to improved treatments in the future. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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+

Published Research Related to This Trial

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]

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 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 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 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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10848821/

Measurement of the Association of Pain with Clinical ... The aim of this study was to compare pain reported by untreated oral cancer patients on the UCSFOCPQ with pain they reported on the Brief Pain Inventory (BPI).

2. withpower.com withpower.com/trial/mechanisms-behind-oral-cancer-pain-353c4

Mechanisms Behind Oral Cancer Pain This N/A medical study run by NYU College of Dentistry is evaluating whether Pain Stimulation Tests will have tolerable side effects & efficacy for patients ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1526590004009381

Evaluation of pain in patients with oral squamous cell ... In this study we have developed and tested a novel pain questionnaire to measure the pain experienced by patients with oral squamous cell carcinoma.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5763394/

Matrix stimulation in cancer pain: Methodology, safety and ... The mean pain reduction achieved by matrix therapy was 30%, under stable daily controlled‐release opioid doses between 177 and 184 mg/day (OME).

5. journals.lww.com journals.lww.com/aomr/fulltext/2021/33020/evaluation_of_pain_management_and_quality_of_life.4.aspx

Evaluation of Pain Management and Quality of Life among... This study aims to assess the pain management and quality of life among patients with cancer of oral cavity, pharynx, and esophagus

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05024383

Dissecting the Heterogeneity of Oral Cancer Pain | ... 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 ...

7. oralmedicinepacific.com oralmedicinepacific.com/wp-content/uploads/2023/07/Oral_pain_in_the_cancer_patient-2022.pdf

REVIEW - Oral pain in the cancer patient Sixty percent of patients reported moderate-to-severe pain in a retrospective study involving 13 827 patients diagnosed with squamous cell carcinoma of the oral ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419316989

Management of cancer pain in adult patients Pain is common in cancer patients, particularly in the advanced stage of disease when the prevalence is estimated to be more than 70%.