Effect of Spinal Ketorolac After Acute Opioid Exposure

Wake Forest University (WFU)

Status and phase: Terminated; Phase 2

Conditions: Healthy

Treatments: Drug: placebo; Drug: remifentanil; Drug: ketorolac; Drug: Capsaicin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00693160

IRB00002457

GM48085

Details and patient eligibility

About

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?

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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30 participants in 2 patient groups, including a placebo group

Intrathecal Ketorolac

Experimental group

Description:

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.

Treatment:

Drug: ketorolac

Drug: Capsaicin

Drug: remifentanil

Placebo intrathecal injection

Placebo Comparator group

Description:

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.

Treatment:

Drug: placebo

Drug: Capsaicin

Drug: remifentanil