The Impact of Epidural Steroid Analgesia on Functional MRI for Patients With LBP
The Impact of Epidural Steroid Analgesia on Functional MRI for Patients With LBP
Chronic low back pain (CLBP) is the most prevalent form of chronic pain, and the most common
 reason for disability in working-age population [2]. CLBP has also been reported associated
 with many abnormal brain anatomy and function which includes the reduction in cortical gray
 matter in the bilateral dorsolateral prefrontal cortex (DLPFC), thalamus, brain stem, primary
 somatosensory cortex, and posterior parietal cortex. [3-5] There are already many studies
 that demonstrated abnormal cortical function for people with CLBP [6-10]. Meanwhile, DLPFC
 was also reported to be influenced by many pain process which included pain modulation
 [11-13], placebo analgesia [14, 15], pain control [16, 17]or pain catastrophizing[18]. And
 recent report has showed that effective treatment of chronic back pain patients reverses
 abnormal DLPFC function[19]. Meanwhile, epidural steroid injection has been performed in
 clinical for routinely managed for low back pain patients. Patients refused or have no
 indication for surgery or have little response to rehabilitation may consider this
 management. There was good evidence for short- and long-term relief of chronic pain secondary
 to disc herniation with local anesthetic and steroids[20, 21]. However, the impact of this
 treatment on functionalMRI (fMRI) has never been investigated. The investigators research
 will try to solve this issue.

 This study will provide a good relationship for the pain fMRI image in brain after local
 lumbar spine management. And the investigators also want to perform the first data that
 showed local lumbar analgesia have the impact on brain image change.
Pain, as an ancient enemy to human kind, was one of the most mystical phenomena within our
 body. For centuries, people search the magic wand to solve this issue and reach the heaven
 destination. However, like our original sin commit by Adam and Eve, the shadow of pain always
 surround and even rebel our body and spirit. Even more, pain traps our soul and body not only
 for the acute stage induced by noxious stimulation but also change our mind and body whenever
 chronic period start even the stimulation disappears. Chronic pain so far has become one of
 the greatest health issues for modern people. Chronic pain affects millions of people and the
 treatment options are quite limited and not effective everyone[1]. On the other way, why and
 how people develop chronic pain, especially when there is no further painful stimulation,
 remain to be investigated.

 Chronic low back pain (CLBP) is the most prevalent form of chronic pain, and the most common
 reason for disability in working-age population [2]. CLBP has also been reported associated
 with many abnormal brain anatomy and function which includes the reduction in cortical gray
 matter in the bilateral dorsolateral prefrontal cortex (DLPFC), thalamus, brain stem, primary
 somatosensory cortex, and posterior parietal cortex. [3-5] There are already many studies
 that demonstrated abnormal cortical function for people with CLBP [6-10]. Meanwhile, DLPFC
 was also reported to be influenced by many pain process which included pain modulation
 [11-13], placebo analgesia [14, 15], pain control [16, 17]or pain catastrophizing[18]. And
 recent report has showed that effective treatment of chronic back pain patients reverses
 abnormal DLPFC function[19]. Meanwhile, epidural steroid injection has been performed in
 clinical for routinely managed for low back pain patients. Patients refused or have no
 indication for surgery or have little response to rehabilitation may consider this
 management. There was good evidence for short- and long-term relief of chronic pain secondary
 to disc herniation with local anesthetic and steroids[20, 21]. However, the impact of this
 treatment on functionalMRI (fMRI) has never been investigated. The investigators research
 will try to solve this issue.

 Patients who first visited in pain clinic for low back pain with root sign will be included
 in this study.

 Inclusion Criteria: 1. Patients with disc herniation or radiculitis who are over 18 years of
 age. 2. Patients with a history of chronic function-limiting low back pain and lower
 extremity pain for at least one months' duration. 3. Patients who are competent to understand
 the study and provide written informed consent and participate in outcome measurements.
 Exclusion Criteria: Patients have previous lumbar surgery with metal instrument. Initial MRI
 shows spinal stenosis or without disc herniation. Patients have unstable opioid use,
 uncontrolled psychiatric disorders, uncontrolled acute medical illness, any condition that
 could interfere with the interpretation of outcome assessments, pregnant or lactating women
 or allergy to local anesthetics or steroid. Patients who are unable to perform MRI or fMRI
 will also be excluded.

 Pre-enrollment evaluation included demographic data, medical and surgical history with
 coexisting disease, lumbar spine X-ray will also be performed.

 After physical neurological examinations, pain questionnaire will be applied for initial pain
 evaluation which includes pain intensity and character and physical activity and emotion
 influence form their pain. Patients then will be performed the first MRI/fMRI study (with the
 MRI informed consent, appendix B) for their lumbar spine and brain condition. Anyone who
 don't have shown spine problem will be excluded for epidural steroid injection. After
 patients' MRI/fMRI evaluation, caudal epidural steroid injection (Regiment: 0.2% lidocaine
 plus kenacort 40 mg for 20 ml,) will then be performed in pain therapy room ( with the
 Epidural informed consent, appendix C). Caudal epidural block will be performed 2-3 times
 with 2 week interval to reach optimal analgesia. The pain condition will be followed every
 month with pain questionnaire for up 3 month. The secondary MRI/fMRI will then be performed 3
 months later after the first caudal epidural steroid injection.

 MRI scans will be acquired on a 3T scanner in NCKU. The special technician will help us and
 the patient for MRI scan and the setting of all MRI parameter. Dr. Sun and a qualified
 radiologist will help for data analysis after MRI performance. The investigators will also
 follow the method that described before[19]: An anatomical scan will be acquired at the
 beginning of the session and lasted 5 min. The following parameters will be used: echo time
 (TE) 3 ms, repetition time (TR) 2.3 s, flip angle 9。, resolution 1*1*1 mm. During a
 functional scan of ~5 min, subjects will perform the Multi-Source Interference Task as
 previous reported[22, 23]. The task stimuli will be presented on a screen in the subjects'
 view while lying in the MRI scanner, and subjects will respond on a three-button response
 box. The task has three levels of difficulty, a motor control task, and easy level and a
 difficult level. The task will enhance the brain network if pain persistent[23]. The
 parameters for functional scan were as follow: echo-planar imaging, TE 3 ms, TR 2.26s, flip
 angle 90。, 128 frames, 64*64 matrix, 38 slices for whole-brain coverage, resolution 4*4*4 mm.
 Images were acquired in the axial plane, plus 30。 from the anterior commissure-posterior
 commissure line to avoid the eyes. The fMRI data analysis will be help under our university
 team.

 Total patients number will be calculated on the basis of significant pain relief and set as
 33 patients with the following statistic parameter: α: 0.05(type I error probability), power
 0.8(probability of correctly rejecting the null hypothesis), δ:0.5(difference in population
 means), σ:1(standard deviation of difference). 20 % noncompliance rate was added and total 40
 patients will be included in this study. According to previous report, 20 more low back
 patients (oral pain control drug plus rehab and refuse epidural steroid injection) were
 needed to include for twice MRI survey.[19]

 Statistical analysis will include the chi-square, Fisher exact test, t test and paired t
 test. The chi-square will be used to test the difference in proportions. Fisher exact test
 will be for whatever the expected value is less than 5; paired t test will used for comparing
 the pre-and post-treatment results. For comparison of mean between groups, t test will be
 done. All the data will be presented as mean ± SEM, and P < 0.05 will be considered
 statistically significant in all cases.

 This study will provide a good relationship for the pain fMRI image in brain after local
 lumbar spine management. And the investigators also want to perform the first data that
 showed local lumbar analgesia have the impact on brain image change.
Inclusion Criteria:

 1. Patients with disc herniation or radiculitis who are over 18 years of age.

 2. Patients with a history of chronic function-limiting low back pain and lower extremity
 pain for at least one months' duration.

 3. Patients who are competent to understand the study and provide written informed
 consent and participate in outcome measurements.

 Exclusion Criteria:

 -  Patients have previous lumbar surgery with metal instrument. Initial MRI shows spinal
 stenosis or without disc herniation. Patients have unstable opioid use, uncontrolled
 psychiatric disorders, uncontrolled acute medical illness, any condition that could
 interfere with the interpretation of outcome assessments, pregnant or lactating women
 or allergy to local anesthetics or steroid. Patients who are unable to perform MRI or
 fMRI will also be excluded.