The Effects of Water Temperature on the Cold Pressor Test

Study Overview
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Brief Summary
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This current study is intended to be completed under the umbrella of the current GHUCCTS IRB- approved study Opioid-Induced Hyperalgesia In Prescription Opioid Abusers: Effects of Pregabalin (Lyrica study) (PRO00000669). In this proposed study, 10 healthy male, 10 healthy female participants and 5 male, 5 female OIH participants (from the parent Lyrica study), who are prescription opioid abusers with chronic pain currently taking Suboxone, will be asked to take the cold pressor test at 1, 5, and 9 degrees Celsius and to report the time at which pain has completely gone away following each test. The purpose of this study is to examine how the water temperature of the cold pressure test might affect the participants' response (i.e., the participants pain threshold and pain tolerance) and to see if there is a difference in how each participation group is affected.

Detailed Description
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Since the 1940s, the cold pressor test (CPT) has been used experimentally as a pain induction method due to its reliability, cost effectiveness and minimal production of side effects. In the CPT, a patient is asked to place his or her hand and forearm in an ice bath until the pain is too great to remain in the water. Researchers have employed the CPT to test a wide range of pain management techniques, including medications, cognitive- based therapies, or acupuncture, as well as to explore pain perception. The CPT has been performed on a variety of participants, including adolescents, drug abusers, and those suffering from chronic back pain. In their classic 1989 paper, Walsh and colleagues developed the normative model of the CPT demonstrating that variations in response are dependent upon age, sex and ethnicity. In 2004, however, Mitchell et al. discovered that the water temperature of the CPT also plays a crucial role in the pain tolerance time of the subjects, noting that a temperature variation of 4°C produced significantly different results for the same subject. While the Mitchell investigations improved upon the standard for the proper CPT technique, as seen implemented in the works of Rash and Campbell, their discoveries were based on healthy individuals. Researchers have explored the CPT responses of patients with an altered pain perception, such as patients with Opioid-Induced Hyperalgesia (OIH), in comparison to healthy controls, demonstrating greater sensitivity in OIH patients. What has not been studied is the effect of temperature on CPT response in OIH patients. Further, the CPT has been shown to have a relatively lengthy recovery time averaging around 10 minutes; however, the recovery time for hypersensitive patients, such as OIH patients, has yet to be studied. As an extension of the work of Mitchell and colleagues, the proposed research will assess the effects of temperature difference and recovery time of the CPT on patients with OIH in comparison to healthy normal control patients. This work is a sub-study of a larger study, Opioid-Induced Hyperalgesia In Prescription Opioid Abusers: Effects of Pregabalin (PRO00000669), conducted by principal investigator Dr. Peggy Compton. The goal of the parent study is to evaluate the ability of pregabalin to diminish chronic low back or arthritic pain and OIH in a sample of prescription opioid abusers (POAs) opioid therapy. This current study is not assigning specific interventions to study subjects. Healthy control and OIH participants will complete all study measures in a single two-hour study session.

Official Title
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The Effects of Water Temperature on the Cold Pressor Test in Patients With Opioid-Induced Hyperalgesia in Comparison to Healthy Controls

Conditions
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Chronic Pain

Intervention / Treatment
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* Other: Cold pressor test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 21 and 65 years old On suboxone or methadone for at least ten days Currently experiencing chronic low back or arthritis pain Exclusion Criteria: Be on any opioid analgesic Have a neurological or psychiatric illness (i.e., schizophrenia, Raynaud's disease, urticaria, stroke) that would affect pain responses Have an abnormal screening EKG, history of heart disease, stroke, liver or kidney disease or acute hepatitis, or currently have a pacemaker or uncontrolled high blood pressure.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prescription opioid abusers<br>Patients 21-65 years old taking suboxone or methadone, currently experiencing chronic pain, not taking any opioid analgesic medication for painful condition on a regular basis, not have any current psychiatric or neurological illnesses, not have a history of heart disease in order to be healthy enough to complete the cold pressor test. | Other: Cold pressor test<br>* The cold pressor test is a procedure used for examining pain threshold and tolerance by subjects placing their forearm in an ice bath. Each participant will take the CPT at 1 °C, 5°C, and 9°C. The first CPT will always be at 1 °C, to ensure participants tolerate the ice bath at the standard temperature. The order of the subsequent CPT at 5°C and 9°C, will be randomized to control for differential carry over effects. Participants will be instructed to say Pain when pain is initially detected (threshold). Then they will be asked to keep the immersed limb in the container until the pain can no longer be tolerated and say Stop and remove the arm from the water when tolerance is reached.<br>|
| Healthy control participants<br>Patients 21-65 years old not taking suboxone or methadone, not experiencing chronic pain, not taking any opioid analgesic medication for painful condition on a regular basis, not have any current psychiatric or neurological illnesses, not have a history of heart disease in order to be healthy enough to complete the cold pressor test. | Other: Cold pressor test<br>* The cold pressor test is a procedure used for examining pain threshold and tolerance by subjects placing their forearm in an ice bath. Each participant will take the CPT at 1 °C, 5°C, and 9°C. The first CPT will always be at 1 °C, to ensure participants tolerate the ice bath at the standard temperature. The order of the subsequent CPT at 5°C and 9°C, will be randomized to control for differential carry over effects. Participants will be instructed to say Pain when pain is initially detected (threshold). Then they will be asked to keep the immersed limb in the container until the pain can no longer be tolerated and say Stop and remove the arm from the water when tolerance is reached.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improved Pain Threshold Response | In a well-described sample of prescription opioid abusers and healthy control subjects, the cold pressor test will be administered to examine how long it takes for a subject to start feeling pain when they immerse their forearm in the cold water (measured in seconds). | 1 two-hour study session | 
| Improved Pain Tolerance Response | In a well-described sample of prescription opioid abusers and healthy control subjects, the cold pressor test will be administered to examine how long subjects' can withstand feeling pain when they immerse their forearm in the cold water (measured in seconds). | 1 two-hour study session | 
| Improved Pain Recovery Response | In a well-described sample of prescription opioid abusers and healthy control subjects, the cold pressor test will be administered to examine how long it takes for subjects' to recover from the pain they experienced when they had their forearm immersed in the cold water (measured in seconds). | 1 two-hour study session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic pain, Narcotic abuse, Opioid related disorders, Opiate substitution treatment, Buprenorphine, Pregabalin, Methadone