Effect of Spinal Ketorolac After Acute Opioid Exposure

Effect of Intrathecal Ketorolac on Mechanical Hypersensitivity Following Acute Opioid Exposure

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):

1. How much does remifentanil (narcotic painkiller) affect the sunburn-like painful area on your skin, which develops after applying capsaicin cream?
2. What pain relieving effects does spinal ketorolac have when given with IV remifentanil?

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: ketorolac; Drug: remifentanil; Drug: Capsaicin; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrathecal Ketorolac; 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; single intrathecal injection of ketorolac 2 mg; Other Names: toradol; acular pf; Drug: remifentanil; All subjects will receive a remifentanil infusion; Other Names: ultiva; Drug: Capsaicin; Topical capsaicin pain model utilized for each subject
Placebo Comparator: Placebo intrathecal injection; 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: remifentanil; All subjects will receive a remifentanil infusion; Other Names: ultiva; Drug: Capsaicin; Topical capsaicin pain model utilized for each subject; Drug: placebo; subject will receive a placebo (preservative free normal saline) spinal injection

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

Collaborators and Investigators

• Sponsor: Wake Forest University
• Collaborators: National Institute of General Medical Sciences (NIGMS)

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: February 15, 2008
• First Submitted That Met QC Criteria: June 3, 2008
• First Posted (Estimate): June 6, 2008

Study Record Updates

• Last Update Posted (Actual): September 7, 2018
• Last Update Submitted That Met QC Criteria: August 8, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: pain; Healthy subjects; healthy volunteers; analgesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Dermatologic Agents; Analgesics, Opioid; Narcotics; Antipruritics; Remifentanil; Ketorolac; Capsaicin
• Other Study ID Numbers: IRB00002457; GM48085

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No