The Effect of Transcutaneous Magnetic Stimulation on Acute Pain.

This is a single institution, single-blinded, long-term exploratory study using participant as his/her own control to evaluate and compare the potential analgesic effect on experimental heat pain of Transcutaneous Magnetic Stimulation (TMS). TMS will be delivered by a commercially available device (Rapid2, Magstim Corp) at three different cortical target sites and one sham target site in healthy participants 18-88 years of age. The quantitative evaluation measure is the change in the painful heat threshold Quantitative Sensory Testing (QST) of thresholds for cutaneous heat stimuli before and after TMS.

After subjects contact the office to express interest in being involved with this protocol, subjects will take the telephone screening questionnaire. Those who meet inclusion criteria with no exclusions will come for first visit. At this visit, subjects will discuss and sign the consent form, and have a one sequence MRI scan which is used to localize sites in the brain to be stimulated with TMS.

The subjects will then have four visits at intervals of two weeks; each visit will have TMS intervention designated (SITE1), (SITE2), (SITE3), and (SITE4). TMS will be applied each of four sites (SITE1, SITE2, SITE3, and SITE4) which will be randomly assigned among stimulation sites Medial Frontal (MF), Dorsolateral Frontal (DL), Primary Motor Cortex (M1 and superior Interparietal sulcus (Sham) and counterbalanced across subjects (see Diagram below).

During each of visits 2 to 5, the participant will undergo baseline Quantitative Sensory Testing (QST), followed by TMS stimulation and then by repeat QST. QST will consist of pain thresholds for cutaneous hot stimuli. Visits 2 through 5 will last for approximately 1 hour each and will occur at two-week intervals. The total study duration will be 50 days for each subject. Study enrollment will last for three years and total study duration will be four years.

Eligibility Criteria:
Inclusion Criteria:

* Healthy man or woman 18-80 years of age;
* Possess the ability to understand study procedures and comply with them for the entire length of the study;
* Women of childbearing age must use contraception for duration of study.

Exclusion Criteria:

* History of diagnosis of heart disease, increased intracranial pressure, or structural abnormalities of the brain (e.g. tumor);
* History of epilepsy, seizure disorder, neurologic disease, cranial trauma or head surgery, or implanted hardware (including cardiac pacemakers, cardiac lines, medication pumps, or stimulators);
* Family history of seizures;
* Presence of metal anywhere deep to or on the skull (excluding the mouth);
* Any current or recent (\<6 weeks) or planned (within duration of study period) use of any of the following medications: imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, ketamine, gamma-hydroxybutyrate (GHB), and theophylline;
* History of peripheral neuropathy, e.g. Diabetic Neuropathy;
* Women who are pregnant or women of childbearing capacity who may become pregnant (i.e. not using contraception);
* Volunteers with communication disorders or non-English speakers;
* Current drug or alcohol use or dependence that, in the opinion of the investigators, would interfere with adherence to study requirements.