Clonidine-induced Spinal Acetylcholine Release: Normal Volunteers vs. Neuropathic Pain

The purpose of this study is to compare the amount of acetylcholine release after a single injection of clonidine in normal volunteers and individuals with neuropathic pain.

This study is part of a pain center grant that focuses on how pain, especially chronic neuropathic pain, alters the response to traditional and non-traditional analgesics (pain medications). The way that nerve fibers carry pain information to the brain is thought to change after surgery and in cases of chronic pain. For this reason, some medicines work better to relieve pain in healthy people who have a sudden painful injury when compared to people after surgery or to people with chronic pain. Currently available pain medications may not relieve all types of pain or may relieve pain only at doses that produce side effects and potential complications. The aim of this study is to understand the mechanisms by which intrathecal clonidine (or clonidine injected into cerebrospinal fluid) increases in potency and efficacy by examining the cerebrospinal fluid of healthy individuals, before and after clonidine administration, as well as looking at the spinal fluid of people with chronic neuropathic nerve pain. More specifically, in this study, researchers will compare acetylcholine release (a protein-like substance found in cerebrospinal fluid) in normal volunteers and patients with neuropathic pain after a single injection of clonidine. After baseline measurements, including blood pressure and heart rate, participants will be trained to accurately estimate pain by way of thermal heat testing. Next a small amount of spinal fluid will be withdrawn from each participant to measure the amounts of naturally-made chemicals in the participants' cerebrospinal fluid. Participants then will receive an injection of clonidine. After the injection, additional samples of spinal fluid will be taken to measure chemical changes in the fluid. Duration of the study for participants is 1 day, and includes 1 visit to the research center, lasting approximately 3 hours.

Chronic Pain Participants will be trained to accurately estimate pain by way of thermal heat testing. Next a small amount of spinal fluid will be withdrawn from each participant to measure the amounts of naturally-made chemicals in the participants' cerebrospinal fluid. Participants then will receive an injection of clonidine. After the injection, additional samples of spinal fluid will be taken to measure chemical changes in the fluid.

Healthy Participants will be trained to accurately estimate pain by way of thermal heat testing. Next a small amount of spinal fluid will be withdrawn from each participant to measure the amounts of naturally-made chemicals in the participants' cerebrospinal fluid. Participants then will receive an injection of clonidine. After the injection, additional samples of spinal fluid will be taken to measure chemical changes in the fluid.

Acetylcholine levels in CSF after administration of intrathecal clonidine measured by High-performance liquid chromatography (HPLC).

Inclusion Criteria: Healthy adult volunteers Patients with neuropathic pain Exclusion Criteria: Pregnancy Allergy to clonidine Currently taking clonidine or other direct a2-adrenergic agonists Taking cholinesterase inhibitors