Clinical Research

Clinical Research is patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator directly interacts with human subjects.

Clinical Research Topics

  • Magnetoencephalographic (MEG) Studies of Patients with Chronic Pain.
  • Clinical Outcomes in Lumbosacral Radiculopathy in Patients Who Have Received Transforaminal vs. Interlaminar Epidural Steroid Injections
  • The Role of Oral Steroids in Prognosticating the Efficacy of Epidural Steroids
  • Optimizing use of Spinal Cord Stimulators in Treatment of Chronic Pain
  • Technical Observation During Epidural Steroid Injections and Their Impact on Clinical Outcomes in Lumbosacral Radiculopathy - Does provocation matter?
  • Brain Rhythms in Trigeminal Neuralgia: A magnetoencephalographic (MEG) study\

Current Clinical Research

Christopher G. Gharibo, MD explains his ongoing research interests.
My research interests are predominantly in the area of interventional options in the care of patients with musculoskeletal and neuropathic pain conditions: Optimizing Safety and Efficacy of Spinal Injections and Use of Spinal Cord Stimulators in Chronic Pain.
 
Lumbosacral radiculopathy occurs in approximately 2% of the population. Initial treatment options for lumbosacral radiculopathy may include a combination of activity modification, a short course of oral steroids, oral analgesics and interventional techniques such as epidural steroids. A short course of an oral steroid such as prednisone has been used for many years with favorable results when managing patients with lumbosacral radiculopathy. We are currently tracking outcome data with a standard dose Prednisone 10mg PO qid and lumbar interlaminar epidural steroid injections. We have started analyzing whether if success or failure with oral prednisone treatment predicts same with interlaminar epidural steroid injection.
 
We have completed data analysis and are authoring a prospective randomized, double-blind study entitles “Clinical Outcomes in Lumbosacral Radiculopathy in Patients Who Have Received Transforaminal vs. Interlaminar Epidural Steroid Injections”. Injection of steroids into the epidural space is a common clinical practice for the treatment of lumbosacral radiculopathy. The presumption is that epidural inflammation irritates the spinal nerve causing radicular pain. The use of epidural steroids is routine in clinical practice and there is controversy in the medical literature whether if there is any difference in outcomes between interlaminar vs. transforaminal epidural steroid injections. In contrast to an interlaminar approach, the transforaminal approach uses fluoroscopy to guide a needle through the neural foramen on one side. This alternate and arguably improved spread of the steroid across the intervertebral foramen may therefore be more effective.
 
We have completed data analysis and are authoring a study entitles “Oral Prednisone Response as an indicator for pain reduction with epidural injection In the treatment of lumbosacral radiculopathy. The data has been accepted for presentation at 2010 American Academy of Pain Medicine Annual Meeting in San Antonio, TX. Lumbosacral radiculopathy occurs in approximately 2% of the population. Initial treatment options for lumbosacral radiculopathy may include a combination of activity modification, a short course of oral steroids, oral analgesics and interventional techniques such as epidural steroids. A short course of an oral steroid such as prednisone has been used for many years with favorable results when managing patients with lumbosacral radiculopathy. We tracked outcome data on successes and failures of Prednisone 10mg PO qid and proceeded to perform a lumbar interlaminar epidural steroid injections on those patients. Patients responded to epidural steroids at the same rate and extent whether or not if they responded to PO steroids. PO steroid do not prognosticate response to epidural steroids.
 
We are looking at efficacy and safety of particulate and nonparticulate epidural steroids in a way that compares different types of clinical practices in the community.
 
For thirty years, spinal cord stimulators (SCS) have been a well-established treatment method for certain chronic pain syndromes. A three to ten day SCS trial begins with percutaneous lead insertion under fluoroscopic guidance, and connection of the lead to a temporary external power source for intra-operative test stimulation. Lead placement requires a dynamic interaction between the patient and the SCS parameter programmer to optimize the SCS settings of amplitude, pulse width, rate, field configuration and pain coverage. The settings of these parameters are often empirical, with programmer attempting many combinations randomly and/or based on personal experience prior to achieving the desired paresthesia coverage. In some cases, the intra-operative test stimulation fails to produce adequate coverage, and the procedure is aborted. My investigational aim is to find parameter settings that have a higher likelihood of providing the desired coverage, particularly low back pain coverage. These settings can facilitate lead placement and programming, improving patient experience and intra-operative efficiency by taking into account patient diagnosis, painful region, lead type, and field configuration.

IBRA CLINICAL PROTOCOL

"Brain Rhythms in Trigeminal Neuralgia: A magnetoencephalographic (MEG) study"

Rodolfo Llinas, MD, PhD, Principal Investigator
Dept. Physiology and Neuroscience 
John J. Delfino, DMD, Co-Investigator

I. PURPOSE OF THE STUDY AND BACKGROUND
1. Purpose of the study and Specific Aims

The ultimate purpose of this research is to understand the pathophysiological basis of chronic pain to provide a framework that will serve as a basis for the development of effective treatment. The purpose of this specific study is to find if there is a brain signature for pain in patients with trigeminal neuralgia (TN). Although TN originates with a peripheral damage of the trigeminal nerve (1), recent studies indicate the presence of changes at the level of the central nervous system (CNS) (2, 3). This is the aspect of TN pain that we will examine. Specifically, we will test the hypothesis that when TN patients are in pain abnormal slow brain rhythms are present that are due to a thalamocortical dysrhythmia (TCD) (described in the Background Section). Thus, we hypothesize that constant low frequency oscillations would be present in TN patients with chronic pain. We expect to see these slow rhythms in two brain areas, the somatosensory cortex (associated with the location of pain) and the mesial frontal cortex (associated with the emotional aspects of pain).
We will use magnetoencephalography (MEG) to non-invasively record brain activity. The MEG data will be analyzed in terms of the presence of normal alpha rhythm and abnormal low frequency oscillations and their source in the person’s brain using their MRI. We will use clinical evaluation, MEG recordings and MRI scans to achieve the following specific aims:

1. To determine if abnormal brain rhythms in the delta (<4Hz) and theta (4-8Hz) frequency bands are present in patients with TN while they are in pain. Our hypothesis predicts that such low frequency activity will be present in TN patients in pain, but not in healthy controls.

2. To determine if brain activity in the gamma (35-55Hz) frequency range is present in TN patients. Our hypothesis predicts that, in TN patients, areas of low frequency activity will have an “edge” area of high frequency activity.

3. To determine if brain activity in the alpha (8-12Hz) frequency range is present in TN patients and it if decreases in MEG recording made with the eyes open compared to recordings with the eyes open. Such normal activity is expected in TN patients and healthy controls.

4. To determine the location of the sources generating abnormal brain rhythms and normal alpha rhythms in TN patients in pain and in healthy controls. Our hypothesis predicts that low frequency regions with high frequency ‘edges’ will have two locations: a) the somatosensory cortex in the region of the face corresponding to affected side, b) the orbitofrontal cortex in portion of the pain pathway associated with the emotional aspects of pain. The source of normal alpha rhythms in both patients and controls will be localized to the posterior brain, particularly the visual cortex.

2. Background

Trigeminal Neuralgia 
Headache is one of the most frequent symptoms in neurology. One of the most debilitating disorders in headaches is cranial neuralgia and central causes of facial pain. Patients with facial pain are labeled as having psychopathology when the etiology is unclear (4). Trigeminal neuralgia, also known as tic doloureux, is defined by the International Headache Society as “a unilateral disorder characterized by brief electric shock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve” (5). In fewer than 5% of patients, the first division is effected. The pain may rarely occur bilaterally, in which case multiple sclerosis must be considered (6). The patient experiences the sensations of pain in the absence of painful sensory stimuli such as washing, shaving, brushing teeth, applying makeup, eating, drinking, talking or being exposed to the wind (4, 7). The incidence of TN in U.S is slightly higher in women (5.9 per 100,000) than men (3.4 per 100,000) (8). The diseases can appear at any age, but in 90% of cases it occurs after 40 years and peaks between 50 and 60 years of age (8). Two distinct subgroups of TN are recognized: classic and symptomatic. In symptomatic TN a demonstrable structural lesion other than vascular compression is present (9).

TN is thought to have a mechanical basis. That is, it results from a proximal compression of the trigeminal root close to the brainstem (1). Indeed, diffusion tensor imaging (DTI) studies have revealed tissue damage on the affected side, but not the unaffected side (10). Changes are not limited to the peripheral nervous system, however. A recent fMRI study has shown changes at the level of the somatosensory cortex (2). Activation of primary and secondary somatosensory cortex was reduced in patients with TN and seemed to be independent of the side of injury and if the pain had been successfully relieved by neurosurgical intervention or not (2). Another study investigated the nociceptive blink reflex (nBR) and brainstem pain-evoked potentials (PREP) in TN patients with and without chronic pain (3). They found prolonged nBR and PREP latencies and reduced amplitudes comparing the affected and unaffected side in both groups of patients. Also, while nBR results were similar across groups, in patients with chronic facial pain, PREP amplitudes were larger and latencies shorter compared to TN patients without facial pain (3). Thus there is evidence for a central component in TN pain. Brain activity in TN patients has not been examined and is the focus of our study.