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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT03164161
Other study ID # BEC-OF-8
Secondary ID
Status Not yet recruiting
Phase N/A
First received September 29, 2016
Last updated May 22, 2017
Start date May 2017
Est. completion date December 2017

Study information

Verified date May 2017
Source Lithuanian University of Health Sciences
Contact Inesa Astramskaite, DDS
Phone +37067694908
Email inesa.astr@gmail.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the correlation between β-endorphin levels in blood plasma and saliva in healthy participants with different pain sensitivity and in those with acute pain in oral and maxillofacial region.

Expected results

- Relation between blood plasma and saliva β-endorphins levels

- Differences of blood plasma β-endorphins levels in healthy participants with different pain sensitivity and in those with acute pain

- Differences of saliva β-endorphins levels in healthy participants with different pain sensitivity and in those with acute pain

- Objective method of patient's pain sensation evaluation

- Correlation between patient's self-reported understanding of pain levels in oral surgery procedures, levels in saliva and blood plasma β-endorphins levels and sensitivity to cold test results

Study protocol:

Selection of participants

1. Evaluation of pain perception in oral surgery procedures by healthy adult participants.

2. Groups formation, according to the results from first stage, resulting in high and low pain rating participants groups.

3. Control group formation from patients with acute pain in oral and maxillofacial region Control rating of participants

1. Patients that have been assigned to groups according to subjective pain ratings in oral surgery procedures will have to repeat the same questionnaire to ensure the correct group assignment.

2. Patients that have been assigned to groups according to subjective pain ratings in oral surgery procedures, will undergo the sensitivity and tolerance to cold pain test.

3. Patients that were assigned to control-acute pain group, will be included in further study stages only with clinically diagnosed cause of acute pain in oral and maxillofacial region to avoid possible psychogenic or general diseases pain.

Evaluation of β-endorphins - sampling

1. Saliva samples will be collected by all further included participants by one selves participants with researchers supervision.

2. Blood samples will be collected from forearm veins by researcher. Evaluation of β-endorphins - laboratorial examination

1. Levels of β-endorphins in saliva and blood will be evaluated according to manufacturer of β-endorphins evaluation kit for human research. Every sample will be evaluated twice and the mean level will be evaluated.

Statistical analysis

1. Statistical analysis will be produced to access all possible relationships


Description:

Fear of dental pain, despite the modern analgesia methods, is still a trigger for many patients, resulting in fear of dentistry. Pain and anxiety during the oral surgery procedures are related to each other. Since fear is a multi-caused state, it is important to analyse each causing factor. Pain sensitivity, or fear of pain, in dental office is different in each person because of various psychological aspects, but also because of genetic code. Pain mechanism is a complex system with many different pathways, resulting in possibility to feel pain. It is interesting that despite the anxiety and stress having a positive correlation with perceived pain, high stress levels may reduce the pain sensation. Stress mechanism involves pain regulation, which may result in hyperalgesia or analgesia. During the stress many organ systems are activated, including the hypothalamic secretion of beta-endorphins, causing analgesia. Therefore, beta-endorphins are secreted by pituitary gland and then spreads to all body by diffusion. However, some studies suggest that beta-endorphins can be also produced by immune cells during the inflammation. Beta-endorphins act like natural morphines, binding the mu-receptors and activating the pain reduction system, therefore beta-endorphin plasma levels correlates with expressed pain. Various studies suggest that low level of peripheral plasma beta-endorphin levels act in chronic pain and trigeminal neuralgia development. Beta-endorphins have also been found as predictive factors to set the overtraining in sports, which result in muscles overloading because of euphoric and analgesic effects. Therefore, investigators have hypothesised that beta-endorphins could be a reliable factor determining patient's pain sensitivity or chronical non-painful processes. Also, since pain rating is usually based on self-reported questionnaires, beta-endorphins evaluation may be possible objective pain evaluation. However, most studies evaluating beta-endorphins levels are based on blood samples evaluation, and blood sampling is a painful and stressful event by itself. Beta-endorphins can also be assessed in saliva, however no previous studies have evaluated the relation between saliva beta-endorphins and plasma beta-endorphins in patients with different pain sensitivity. The aim of this study is to evaluate the relationship between plasma beta-endorphin and saliva beta-endorphin levels in patients with different pain sensitivity and patients with acute pain in maxillofacial region.

Study design

- Assessment: Healthy participants will be assessed in two groups regarding the evaluation of pain in common procedures in oral surgery self-reported questionnaire. The questionnaire is composed from 10 items, including perception of pain during surgical procedures and perception of post-operative healing caused pain. Procedures, such as anaesthetic injection, wisdom tooth removal, mobile tooth extraction, stitches removal, implantation and incision are composed into questionnaire. All items must be rated in numerical rating scales (NRS) from 1 - no pain to 10 - extreme pain, according to patient's assumption. Participants to further clinical trial will be randomly selected to form two groups with low and high pain rating. Further involved participants will have to repeat pain rating questionnaires to avoid possible accidental items rating. Cold pressor test will be enrolled for both groups in further described method.

- Cold pressor test. Participants will have to hold their hand up to the wrist in 5° temperature water, since it was suggested as a medium temperature giving the results of appropriate test time and felt pain. The water temperature below 15°C is known to stimulate nociceptors and provoke pain, however the testing time is relatively to long and the minimum temperature to this test of -2°C quickly provokes pain and it encumbers time evaluation. Digital thermometer will be used to ensure even temperature during the test with error of 0,5°C. The time of first painful sensation (pain threshold) will be noted and patients will be asked to self-report the felt pain in 1-10 NRS, afterwards the time of hand withdraw will be also recorded (pain tolerance) and the pain will be rated as described before. The maximum time of the test will be 4 minutes. If at the end of 4 minutes patient is still continuing, he will be asked to rate pain felt at 4 minutes moment in 10 points NRS and the test will be withdraw.

- Patients to control - acute pain group will be assessed randomly from those, coming for help because of acute pain in oral and maxillofacial region. Patients will be asked to voluntarily participate in research, with the aim of best patient's care and least interference to the needed treatment procedures. Only patients with clinically diagnosed cause of acute pain will be enrolled, even though it is stated that pain is present for patient, whenever a patient reports pain, with the aim to avoid any psychogenic pain. Also, patients will be asked to rate their present pain in NRS and only those assessing pain not less than 4 out of 10 points will be further included, since it is described as moderate pain at 4-6 points and severe pain at 7-10 points. Also, NRS is known as appropriate numerical method, if pain is empirically tested.

- Β-endorphins evaluation. Participants from non-acute-pain group will be tested the other day than cold-pressor test to eliminate the effect of pain pressor test stimulated stress, resulting in sympathetic system activation, including β-endorphins production. Before the sampling patients will be asked to calm and stay still until they feel relaxed to avoid possible stress effect on results. The saliva samples will be collected by participants with researcher's supervision in sterile test-tubes. It is known that β-endorphins can be found in saliva, however it is not commonly used in pain evaluating researches. Afterwards the blood sampling will be provided with the aim not to produce blood collection caused stress before saliva sampling. Blood samples will be used as control samples to ensure the presence of β-endorphins in organism at exact moment and to rate the blood β-endorphins concentrations relation with saliva β-endorphin levels.

- Β-endorphins sampling in control - acute pain group will be provided at the same day as acute pain is felt. This group will be used as control, since it is presumed that acute pain and stress increases β-endorphins levels. Saliva sample will be collected by participant under the researcher's supervision. Afterwards the blood sample will be collected.

- Laboratorial examination. Will be performed according to manufacturer's recommendations.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 100
Est. completion date December 2017
Est. primary completion date December 2017
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Patients without reported chronical or acute pain in non-acute-pain group

- Patients with acute pain in oral and maxillofacial region with diagnosed cause of pain in acute-pain group

- Patients older than 18 years

Exclusion Criteria:

- Patients undertaking any pain relieving medicine, including non-steroid and opioid medicine

- Patients with diagnosed endocrine system diseases

- Patients with psychogenic diseases

- Patients with pre-injected local anaesthetics

- Patients with oncologic diseases

- Patients with endocrine system diseases

Study Design


Related Conditions & MeSH terms


Intervention

Device:
Cold pressor test
Described before.
Other:
ß-endorphins evaluation in saliva
Described before.
ß-endorphins evaluation in blood plasma
Described before.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Lithuanian University of Health Sciences

References & Publications (27)

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Astramskaite I, Poškevicius L, Juodžbalys G. Factors determining tooth extraction anxiety and fear in adult dental patients: a systematic review. Int J Oral Maxillofac Surg. 2016 Dec;45(12):1630-1643. doi: 10.1016/j.ijom.2016.06.019. Epub 2016 Jul 18. Review. — View Citation

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Dalayeun JF, Norès JM, Bergal S. Physiology of beta-endorphins. A close-up view and a review of the literature. Biomed Pharmacother. 1993;47(8):311-20. Review. — View Citation

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Klages U, Ulusoy O, Kianifard S, Wehrbein H. Dental trait anxiety and pain sensitivity as predictors of expected and experienced pain in stressful dental procedures. Eur J Oral Sci. 2004 Dec;112(6):477-83. — View Citation

Koenig J, Jarczok MN, Ellis RJ, Bach C, Thayer JF, Hillecke TK. Two-week test-retest stability of the cold pressor task procedure at two different temperatures as a measure of pain threshold and tolerance. Pain Pract. 2014 Mar;14(3):E126-35. doi: 10.1111/papr.12142. Epub 2013 Nov 20. — View Citation

Kyle BN, McNeil DW, Weaver B, Wilson T. Recall of Dental Pain and Anxiety in a Cohort of Oral Surgery Patients. J Dent Res. 2016 Jun;95(6):629-34. doi: 10.1177/0022034516631977. Epub 2016 Feb 23. — View Citation

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Mourot L, Bouhaddi M, Regnard J. Effects of the cold pressor test on cardiac autonomic control in normal subjects. Physiol Res. 2009;58(1):83-91. Epub 2008 Jan 17. — View Citation

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Pain: clinical manual for nursing practice Pain: clinical manual for nursing practice Margo McCaffery Alexander Beebe Mosby Yearbook UK £17.25 0 7234 1992 2. Nurs Stand. 1994 Dec 7;9(11):55. doi: 10.7748/ns.9.11.55.s69. — View Citation

Rai B, Kaur J. Salivary stress markers and psychological stress in simulated microgravity: 21 days in 6° head-down tilt. J Oral Sci. 2011 Mar;53(1):103-7. — View Citation

Randall CL, McNeil DW, Shaffer JR, Crout RJ, Weyant RJ, Marazita ML. Fear of Pain Mediates the Association between MC1R Genotype and Dental Fear. J Dent Res. 2016 Sep;95(10):1132-7. doi: 10.1177/0022034516661151. — View Citation

Saltychev M, Vastamäki H, Mattie R, McCormick Z, Vastamäki M, Laimi K. Psychometric Properties of the Pain Numeric Rating Scale When Applied to Multiple Body Regions among Professional Musicians. PLoS One. 2016 Sep 7;11(9):e0161874. doi: 10.1371/journal.pone.0161874. eCollection 2016. — View Citation

Sanikop S, Agrawal P, Patil S. Relationship between dental anxiety and pain perception during scaling. J Oral Sci. 2011 Sep;53(3):341-8. — View Citation

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V Nikolov, M Petkova, B Petrova, K Mineva. Pain perception to the cold pressor test in reproductive - age women: relation to menstrual phase and comparison with men. Trakia J Sci. 12(1):376-380, 2014

Wolf S, Hardy JD. STUDIES ON PAIN. OBSERVATIONS ON PAIN DUE TO LOCAL COOLING AND ON FACTORS INVOLVED IN THE "COLD PRESSOR" EFFECT. J Clin Invest. 1941 Sep;20(5):521-33. — View Citation

Zhao YF, Jiang XZ, Hu SH, Liu Y, Miao L, Song CY. [Observation of plasma levels of beta-endorphin in patients with trigeminal neuralgia]. Shanghai Kou Qiang Yi Xue. 2001 Mar;10(1):46-8. Chinese. — View Citation

* Note: There are 27 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Correlations between ß-endorphins levels (pg/mL) and cold pressor test (min:s), pain perception (1-10 points) questionnaire results. Both, saliva and blood ß-endorphins levels will be compared with cold pressor test results and pain perception in oral surgery test results. Blood ß-endorphin levels will be used only as control measurement, focusing on saliva ß-endorphin levels correlation. One year
Secondary Differences between acute-pain group and healthy participants groups with different pain sensitivity levels All data will be compared between acute-pain and healthy participants groups, to determine, if acute-pain causes ß-endorphin levels change. One year
Secondary Correlation between saliva ß-endorphins and blood plasma ß-endorphins levels Correlations between saliva and blood plasma ß-endorphin levels will be calculated with the necessity to collect both samples at the same day and to do laboratorial examinations twice for each sample. One day
Secondary Correlation between pain perception in oral surgery questionnaire and cold pressor test results Possible correlations between pain perception in oral surgery questionnaire results and various results from cold pressor test will be calculated. Time (min:s) and pain rating points (1-10) will be taken from cold pressor test and compared with questionnaires points sum (1-100) One year
Secondary Pain perception in oral surgery questionnaire test - retest correlation Correlation between primary questionnaire rating and secondary questionnaire rating on pain pressor test day will be calculated. One year
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