Effect of Spinal Ketorolac After Acute Opioid Exposure

Phase 2

Terminated

Conditions: Healthy

Interventions: Drug: ketorolac
Drug: placebo
Drug: remifentanil
Drug: Capsaicin

Registration Number: NCT00693160

Lead Sponsor: Wake Forest University

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):

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?

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 30

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intrathecal Ketorolac	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.
Placebo intrathecal injection	placebo	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.
Placebo intrathecal injection	Capsaicin	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.
Intrathecal Ketorolac	remifentanil	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.
Intrathecal Ketorolac	Capsaicin	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.
Placebo intrathecal injection	remifentanil	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.

Primary Outcome Measures

Name	Time	Method
Hyperalgesia	24 hours	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

Secondary Outcome Measures

Name	Time	Method
Cerebrospinal Fluid (CSF) Prostaglandin E2 (PGE2) Concentration	2.5 hours	Concentration of prostaglandin E2 (PGE2) in Cerebrospinal fluid (CSF) 2.5 hours post injection of intrathecal ketorolac