Effect of Spinal Ketorolac After Acute Opioid Exposure

Study Overview
=================
Brief Summary
-----------------
This research study is being done because pain is a significant problem for patients with a variety of medical problems and following surgery or traumatic injury. Currently available pain medications may not treat all types of pain or may treat pain only at doses that produce side effects and complications. The medication in this study may have a role in better treatment of pain. The goals of this study are to see if a dose of ketorolac (non-narcotic, pain reliever), given into the fluid in the back near the spine has any effect on pain or discomfort in the skin sensation that will take place after applying capsaicin (chili pepper) cream. The sunburn-like sensation that people experience after having capsaicin cream applied is similar to, but much milder than, the pain that some people have after surgery and after certain types of nerve injuries. This study will test the effects of combining two medications that are often given together to control postoperative pain or pain from a nerve injury. The investigators are especially interested in answering two questions about the effects of ketorolac (non-narcotic pain reliever) and remifentanil (intravenous [IV] narcotic painkiller): How much does remifentanil (narcotic painkiller) affect the sunburn-like painful area on your skin, which develops after applying capsaicin cream? What pain relieving effects does spinal ketorolac have when given with IV remifentanil?

Detailed Description
-----------------
Intravenous (IV) remifentanil stimulates spinal COX activity, leading to increased Cerebrospinal fluid CSF) prostaglandin E2 (PGE2) concentrations and areas of capsaicin-induced mechanical hypersensitivity after remifentanil infusion, and these effects will be blocked by intrathecal ketorolac. Areas of mechanical hyperalgesia and allodynia will be established by topical capsaicin + intermittent heat in healthy volunteers, who will be randomized to receive intrathecal saline or ketorolac during remifentanil infusion, with primary outcome measure area of hyperalgesia and secondary outcome measure Cerebrospinal fluid (CSF) prostaglandin E2 (PGE2) concentration after stopping remifentanil.

Official Title
-----------------
Effect of Intrathecal Ketorolac on Mechanical Hypersensitivity Following Acute Opioid Exposure

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: ketorolac
* Drug: placebo
* Drug: remifentanil
* Drug: Capsaicin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: healthy American Society of Anesthesiologist (ASA) I or II classification between the ages of 18-55 weigh less than 250 pounds without chronic pain Exclusion Criteria: taking analgesics in the last 2 weeks positive urine drug screen pregnancy currently taking any prescription antidepressants or other medications that are mood altering liver or kidney disease stomach ulcers allergies to ketorolac, lidocaine, or capsaicin cream lung disease (COPD)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intrathecal Ketorolac<br>In the presence of a remifentanil infusion subject will receive a single intrathecal injection of ketorolac 2 mg Each subject will receive the topical capsaicin model for hyperalgesia and allodynia assessment. | Drug: ketorolac<br>* single intrathecal injection of ketorolac 2 mg<br>* Other names: acular pf;Drug: remifentanil<br>* All subjects will receive a remifentanil infusion<br>* Other names: ultiva;Drug: Capsaicin<br>* Topical capsaicin pain model utilized for each subject<br>|
| Placebo Comparator: Placebo intrathecal injection<br>In the presence of remifentanil the subject will receive a single intrathecal injection of placebo (preservative-free normal saline) Each subject will receive the topical capsaicin model for hyperalgesia and allodynia assessment. | Drug: placebo<br>* subject will receive a placebo (preservative free normal saline) spinal injection<br>Drug: remifentanil<br>* All subjects will receive a remifentanil infusion<br>* Other names: ultiva;Drug: Capsaicin<br>* Topical capsaicin pain model utilized for each subject<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyperalgesia | Total Area of hypersensitivity (measured in centimeters) were assessed approximately 24 hours post intrathecal ketorolac injection by the method of using a von Frey filament | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebrospinal Fluid (CSF) Prostaglandin E2 (PGE2) Concentration | Concentration of prostaglandin E2 (PGE2) in Cerebrospinal fluid (CSF) 2.5 hours post injection of intrathecal ketorolac | 2.5 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
analgesia, healthy volunteers, pain, Healthy subjects