The Effect of Central Sensitization on the Treatment Success of Ultrasound-Guided Caudal Epidural Steroid Injection in Radicular Pain in Patients With Failed Back Surgery Syndrome
Conditions: Herniated Disc, Failed Back Surgery Syndrome
Sponsor: Marmara University

 
 
 
 
 
 
                                        
 
1- NAME OF THE PROJECT 
“The Effect of Central Sensitization on the Treatment Success of Ultrasound-Guided Caudal 
Epidural Steroid Injection in Radicular Pain in Patients with Failed Back Surgery Syndrome” 
 
2-QUALITY OF THE RESEARCH 
Non-Pharmaceutical Prospective Observational Clinical Trial 
 
3- IN MULTI-CENTER RESEARCH, CENTERS OUTSIDE THE INSTITUTION : 
The research is not multicenter. 
 
 
9-JUSTIFICATION / PURPOSE OF THE STUDY : 
 
Low back pain is a very common clinical entity that has a tremendous social, financial and 
psychological impact on the patient's life. It is a worldwide problem, with a global incidence of 9.4%, 
and causes more disability than any other condition in the world. The percentage of adults who 
experience chronic low back pain throughout their lives varies between 51% and 84% (1). As the 
population ages, the incidence of surgery for low back pain increases dramatically; The number of 
lumbar fusions increased by as much as 170% from 1998 to 2008 (2). Failed back surgery syndrome 
(FBSS) has been reported to affect 10 to 40% of patients following spine surgery, but estimating the 
incidence of FBSS is difficult due to the broad scope of its definition and heterogeneous etiology ( 3 ). 
Failed back surgery syndrome (FBSS) is defined by the International Association for the Study of Pain 
as "lumbar spinal pain of unknown origin that persists despite surgical intervention or occurs after 
surgical intervention for pain in the same topographic area" (4). Pain may occur after surgery, as surgery 
may aggravate or fail to adequately heal existing pain. Patients with FBSS have long-standing chronic 
low back pain, with or without radicular symptoms, and have had one or more surgical interventions 
that do not treat the pain. Its etiology is complex and it is a condition with many factors that predispose 
patients to chronic pain. Epidural fibrosis, perineural scars, acquired stenosis, recurrent disc herniation 
or pain in the sacroiliac/facet joints are thought to play a role in the etiology of FBSS. Pain in the leg 
likely indicates nerve compression resulting from stenosis, epidural fibrosis, or disc herniation, while 
lower back pain is more common in facet joint arthropathy, sacroiliac joint problems, or myofascial 
etiologies . For the failed back surgery syndrome patient, physical examination is generally not useful 
 
03.03.2023

 
 
 
 
 
 
in determining a specific pain etiology, but may reveal several suggestive findings. Symptoms resulting 
from spinal stenosis are usually exacerbated by spinal extension and relieved by flexion. On the other 
hand, pain from disc herniation causes a positive straight leg raise test. Loss of strength or sensation in 
the lower extremities can help figure out which nerve roots are affected. Other tests may be used to 
elucidate the etiology of failed back surgery syndrome and differentiate it from other causes of low back 
pain. Erythrocyte sedimentation rate and C-reactive protein can be used to evaluate possible infection, 
especially in patients with constitutional symptoms or a predisposition to infection. Diagnostic nerve 
blocks can diagnose specific etiologies of FBSS, such as facet joint arthropathy (medial branch blocks), 
sacroiliac joint pain (lateral branch blocks and intra-articular injection), and foraminal stenosis 
(transforaminal epidural and selective single-level blocks) and roots associated with the patient's 
symptoms. can define. MRI with and without gadolinium contrast remains the gold standard imaging 
modality for failed back surgery syndrome due to its excellent ability to detect soft tissue abnormalities 
such as epidural fibrosis and disc herniation. Contrast is especially indicated in patients with a history 
of disc herniation surgery. An international panel of spine surgeons, neurosurgeons and pain specialists 
with a special interest in FBSS established the Chronic Low Back and Leg Pain (CBLP) network to 
address challenges and barriers in the clinical management of FBSS patients by creating a common 
interdisciplinary structure. The definition of FBSS proposed by the CBLP network is based on the 
prediction that no further spine surgery is required after an appropriate somatic, radiological and 
psychosocial evaluation (5). The key elements for the definition of FBSS can be summarized in 4 
aspects: 
1. There is back and/or leg pain that has persisted for at least 6 months after the most recent spine 
surgery. 
2.The patient has undergone a comprehensive clinical and radiological evaluation 
3.There is no clear surgical target compatible with the symptoms revealed on clinical examination and 
imaging 
4. There is an interdisciplinary consensus that additional surgical intervention (decompression and/or 
fusion) is not appropriate 
Despite its adverse effects on patients and its relative prevalence in the population undergoing spine 
surgery, there are few high-quality randomized trials investigating the treatment of FBSS. (6). 
Treatments for FBSS are generally divided into conservative (physical therapy or drug therapy) and 
aggressive (interventional or surgical) management. Conservative treatment should always be the first 
choice before invasive techniques in patients who do not have an indication for urgent surgery (7). 
Various studies have shown that caudal ESI (CESI) is an effective method in patients with FBSS who 
do not respond to conservative pain-relieving treatments (8). Çelenlioğlu A. et al. In a prospective 
randomized study comparing the treatment success of TFESI and CESI in patients who developed FBSS 
after single-level discectomy, both CESI and TFESI (transforaminal epidural steroid injection) were 

 
 
 
 
 
 
found to be effective and safe in treatment. CESI has been shown to be the safest and simplest ESI with 
a low rate of complications, including dural puncture and other side effects, compared to other injection 
methods (9). Yoon et al. (10) reported the success rate of US-guided caudal blockade as 94% (11). In a 
study conducted by Akkaya et al. (12), comparing ultrasound and fluoroscopy-guided caudal epidural 
steroid injection (CESI) in patients with FBSS, a decrease in both pain and ODI scores was achieved in 
both groups at 3-month follow-up, and CESI was found to be effective in the treatment of FBSS. has 
been reported. In a prospective randomized controlled study comparing the treatment success of caudal 
epidural steroid injection guided by ultrasonography (USG) and fluoroscopy in postlaminectomy 
patients, no difference was found in terms of complications between the two groups, while patients in 
the fluoroscopy group felt more pain during the intervention than patients in the USG group. Despite 
accurate needle localization and drug injection under fluoroscopic guidance, radiation is still a serious 
risk for both the patient and the interventionalist. The use of USG in caudal epidural injections protects 
against radiation exposure and is a safe and rapid method to locate the sacral hiatus and guide the needle 
(9). Color Doppler USG can visualize intravenous injections. Tsui et al. (13) reported that the color 
Doppler feature of US can confirm whether the injected drug diffuses into the caudal area. Injection of 
fluid into the epidural space causes turbulent flow, which appears as a burst of color, whereas intrathecal 
injection shows the absence of color flow Doppler signal. Although the exact pathophysiological 
process of FBSS remains unclear, increasing evidence suggests that the symptoms of diffuse pain 
distribution, hyperalgesia, and disproportionate pain intensity, which are also common in other chronic 
pain-related diseases (e.g., fibromyalgia, tension-type headache, and nonspecific chronic low back 
pain), are a potential pain disorder. predicts that central sensitization may develop (14). The 
International Association for the Study of Pain (IASP) defined CS in 2011 as “the increased response 
of nociceptive neurons in the central nervous system to normal or subthreshold afferent input.” Anxiety 
about pain, limitation of daily activities, quality of life and related stress lead to depression over time, 
thus beginning a vicious "pain-anxiety-depression" cycle. Altered central pain modulation may be 
involved in the pathogenesis of FBSS. Unfortunately, only a few studies have investigated the presence 
of central sensitization in patients with FBSS, although it may guide treatment. Central amplification 
of pain may contribute to both chronic low back pain intensity and disability in FBSS patients. 
Therefore, targeted treatments should take into account functional changes in the central nervous system 
of FBSS patients, and treatment modalities that can attenuate central sensitization (e.g., cognitive 
targeted exercise therapy, pharmacotherapy, spinal cord stimulation) may be useful in the treatment of 
FBSS. Our aim is to reveal the relationship between FBSS and central sensitization proportionally, to 
prevent the formation of a vicious circle of chronic pain with early detection and treatment, keeping in 
mind that central sensitization may develop in postspinal surgery patients with ongoing pain, and also 
to prevent the formation of a vicious cycle of chronic pain with USG-guided caudal epidural steroid 
injection, as there is no radiation exposure and it is advantageous and beneficial. Since it is a reliable 

 
 
 
 
 
 
method, we aim to determine its effectiveness in patients with FBSS. To our knowledge, such a study 
has not been reported before in the literature. We hope to contribute to the literature. 
 

 
 
 
 
 
 
  
 
10-APPROACHES AND METHODS TO BE APPLIED : 
 
 
Among the patients who applied to Marmara University Pendik Training and Research Hospital, 
Physical Medicine and Rehabilitation and Algology outpatient clinics with complaints of low back pain, 
were diagnosed with FBSS by Algology after clinical, physical examination and radiological imaging 
and were planned for caudal epidural steroid injection, which is a treatment option applied in routine 
clinical practice. Those who meet the exclusion criteria will be included in the study after detailed 
information about the research is given and their verbal and written consent is obtained. These patients 
will not undergo additional treatment, any imaging methods or laboratory tests. Patients diagnosed with 
or in contact with Covid-19 will not be processed until the quarantine period expires. Patients will be 
reminded to comply with the mask and distance rules in the waiting area before the procedure and in 
the observation area after the procedure, not to touch any surfaces in the hospital unless necessary, and 
to frequently disinfect their hands. During the evaluations, the patient and the physician; will comply 
with mask, distance and hand hygiene rules. After the procedure, a waiting area will be allocated for 
patients in accordance with distance rules. 
 
 
Patients who meet the Chronic Low Back and Leg Pain consensus group FBSS definition and meet the 
inclusion criteria will be included in the study. Before the patients are processed, data such as 
demographics, height, weight, which leg the pain is on, additional diseases, and medications used will 
be recorded. Before the procedure, patients will be evaluated with scales and methods such as Numeric 
Rating Scale (NRS), Oswestry Disability Index (ODI), Central Sensitization Inventory (CSI), Beck 
Depression Inventory (BDI), Douleur Neuropathic 4 (DN4) and a pressure algometer (baseline brand 
manual Quantitative sensory testing will be performed using algometer) . Those who score 40 and above 
on CSI will be included in Group 1 (those with CS), and those with lower scores will be included in 
Group 2 (those without CS). Homogeneity between groups will be ensured in terms of the surgical 
method applied (lumbar stabilization or microdiscectomy) and etiological cause (fibrosis and recurrent 
disc herniation). Patients in both groups will undergo CESI under USG guidance. Patients will be re-
evaluated with NRS at 1 hour, 3 weeks and 3 months after the procedure, using the scales and methods 
mentioned above. A 50% or more reduction in NRS in the 3rd month will be considered treatment 
success. 
 

 
 
 
 
 
 
 
Numeric Rating Scale (NRS) is a scale in which the patient gives a score between "0" and "10" for the 
back and leg pain felt, where "0" = no pain and "10" = the most severe, unbearable pain. is a scale. 
Turkish validity and reliability studies of the scales and surveys to be used in the study have been 
conducted and are stated in the references. 
The Central Sensitization Inventory (CSI) includes 2 parts: part A, which evaluates symptoms thought 
to be related to CS, and part B, which quickly questions whether the patient has previously received a 
specific diagnosis. Part A contains 25 items that question the frequency of symptoms seen in SS 
syndromes and are scored between 0-100 points. Each symptom is defined as "never" (0 points) if the 
patient never experiences that symptom, "rarely" (1 point) if the patient experiences it rarely, 
"sometimes" (2 points) if he sometimes experiences it, "often" (3 points) if he frequently experiences 
it, "frequently" (3 points) if he always experiences it. It is recorded as “always” (4 points). As the 
patient's score increases, he or she is considered to have more symptoms related to CS. 
Beck Depression Inventory (BDI) was created by Beck in 1961 to measure the characteristic attitudes 
and depression symptoms of patients. The survey consists of a total of 21 questions, each with four 
options. Each option is scored between 0-3 and the total score is calculated. In scoring, 0-9 is interpreted 
as normal, 10-18 as mild depression, 19-29 as moderate depression, and 30-63 as severe depression 
(15). 
Oswestry Disability Index (ODI) consists of 10 items. Items question the severity of pain, self-care, 
lifting, carrying, walking, sitting, standing, sleeping, degree of pain change, travel and social life. There 
are 6 statements under each item, in which the patient ticks the one appropriate to his/her situation. The 
first statement is scored as “0” and the 6th statement is scored as “5”. When the total score is calculated, 
it is multiplied by 2 and expressed as a percentage. The maximum score is "100" and the minimum 
score is "0". As the total score increases, the disability level also increases. 
Quantitative Sensorial Testing (QST) is widely used in human research to investigate the contributions 
of the peripheral and central nervous system to pain modulation. Pressure pain threshold (PPT) 
measurements are also a frequently used evaluation method among QST. PPT measurements will be 
measured using two different regions in each patient; areas with maximum pain at the waist for group 
1 (those with CS), 3 cm adjacent to the L5 spinous process (local area) for group 2 (those without CS); 
and the dominant hand (approximately in the middle of the proximal transverse arch) for all subjects 
(far pain-free area). PPT will be evaluated three times in each region, with at least 60 seconds between 
stimuli, and the average of these 3 evaluations will be recorded as the PPT value for this region. If 
patients fail to report pain to a pressure of 10 kg/cm2, the test will be stopped and this value will be 
recorded as PPT. 

 
 
 
 
 
 
Douleur Neuropathic 4 (DN4) is a scale that evaluates the patient's neuropathic symptoms with 4 
questions. On a scale with a total score of 10, those with scores above 4 indicate the presence of 
neuropathic pain. 
 
 
 
Processing Technique 
Caudal Epidural Steroid Injection (CESI): 
CESI procedure, which is a treatment method applied in routine clinical practice in patients diagnosed 
with FBSS who do not respond to conservative treatments, will be performed by an algologist (ŞŞ or 
OHG) with at least 10 years of experience in this field. During the procedure, the distance rule will be 
observed as much as possible (the person performing the procedure must be as close to the patient). 
After patients are placed in the prone position, a pillow will be placed under the patient's abdomen to 
reduce lumbar lordosis. The injection site will be cleaned three times with povidone-iodine antiseptic 
and then covered with a sterile drape. In the operating room, patients will receive standard monitoring 
(ECG, MAP, SpO2) and vascular access will be established with a 20 G branule. Short-acting local 
anesthesia (3 mL 2% prilocaine) will be applied to the skin and subcutaneous tissue. A 3.5-inch, 22-
gauge spinal needle will be inserted into the caudal epidural space, verifying that the needle does not 
exceed the level of the S3 foramen. 1- 2 mL contrast material (300 mg/50 ml iohexol) will be 
administered and the distribution of the injectate will be monitored simultaneously in Doppler mode, 
and the distribution pattern showing bilateral L5-S3 spread without vascular spread will be displayed. 
A mixture of 40 mg (1 mL) triamcinolone acetonide, 7 mL physiological saline and 2 mL (0.5%) 
bupivacaine will be injected, a total of 10 mL mixture will be used, all patients will be monitored and 
evaluated for one hour after the procedure. Patients without any procedural complications will be 
discharged. 
 
 
 
Power analysis 
According to the study conducted by Sacaklı R. et al., based on the improvement in pain scores in the 
3rd month, the number of samples was found to be 21 for the CS group and 25 for the non-CS group, 
with a 95% confidence interval and 90% power. Considering that 10% of the patients could not continue 
the study, a total of 51 patients were planned to be included. 

 
 
 
 
 
 
Sacakli, R., Sanal-Toprak, C., Yucel, FN, Gunduz, OH, & Sencan, S. (2022). The Effect of Central Sensitization on Interlaminar Epidural 
Steroid Injection Treatment Outcomes in Patients with Cervical Disc Herniation: An Observational Study. Pain Physician, 25(6), E823-E829. 
 
 
 
 
 
D-OTHER INFORMATION ABOUT VOLUNTEERS 
Minimum 
number of 
volunteers to be 
included in the 
study 
Total 
Age range 
Group-1 
CS ones 
24 
 
18-75 
Group-2 
non-CS 
27 
18-75 
 
 
 
 
 
 
 
 
12- CRITERIA FOR INCLUSION, EXCLUSION AND REMOVAL FROM THE RESEARCH 
 
 
INCLUDING: 
● Being between the ages of 18-75 
● Those who meet FBSS diagnostic criteria (according to CBLP) 
● Radicular pain that begins at any time after surgery and persists for at least 6 months 
● Those with clinically compatible epidural fibrosis and/or disc herniation at the L5 and/or S1 
vertebra level on contrast-enhanced MRI 
● Nrs is greater than or equal to 4 
● Failure to achieve significant improvement with conservative methods 

 
 
 
 
 
 
● Volunteering to participate in the study and signing a consent form 
 
 
EXCLUSION: 
● Those with acute or chronic uncontrolled medical illness, 
● Lumbar structural pathologies (e.g., traumatic spinal injuries, infections, tumor and ankylosing 
spondylitis) 
● Those with isolated axial low back pain 
● Those with a history of lumbar surgery other than lumbar stabilization or microdiscectomy 
● History of adverse reactions to local anesthesia or steroids 
● Being pregnant or breastfeeding 
● History of allergy to the injectables to be administered 
● Those with bleeding diathesis 
● Mental, psychiatric or neurological diagnosis that may complicate the implementation of the 
study 
● Not wanting to participate in the study 
 
 
 
VOLUNTARY CONSENT FORM (Separate Page) 
I read the text above showing the information that should be given to the volunteer before the 
research. Written and verbal explanations were given to me about these. Under these conditions, I 
agree to participate in the clinical research in question with my own consent, without any pressure or 
coercion. 
Due to the ongoing Covid-19 epidemic, the precautions to be taken during the process are listed 
below: 
1. In the evaluations to be made before the procedure, the patient and the physician; will 
comply with basic rules such as mask, distance and hand hygiene. 
2. Before the procedure, the area where patients wait will be wide enough and mask and 
distance rules will be observed. 
3. Our patients who are diagnosed with or have been in contact with Covid-19 will not be 
treated until the quarantine period expires. 

 
 
 
 
 
 
4. During the procedure, the mask and distance rules will be followed as much as possible (the 
physician performing the procedure must be at a close distance to you). 
5. After the procedure, mask and distance rules will be observed in the waiting area. 
 
 
Volunteer: 
Name-Surname:  
Signature: 
Address/Phone: 
 
 
Parent/Guardian: 
Name-Surname:  
Signature: 
Address/Phone: 
 
 
The researcher: 
Name and surname: 
Signature: 
 
 
Name-surname, signature and position of the organization official who witnessed the consent process 
from beginning to end 
 
 
 
 
 
 
 
 
 
 
 
 
ANNEX-II 
 

 
 
 
 
 
 
PATIENT FOLLOW-UP FORM 
Name surname: 
 
History: 
Phone: 
TC Identification number : 
Age: 
 
Address: 
Gender: 
 
Kilo: 
Size: 
BMI: 
Marital status: □ Married  
□Single 
Occupation: □ Housewife □ Student □ Civil servant □ Worker  □ Retired 
Educational status: □ Illiterate  □Literate □ Primary school  
□Middle school  
□High 
school 
□ College □ University 
 
Previous surgery; 
The party to be transacted; Duration of symptoms: Comorbidity: 
Radicular pain; Previous treatments / duration : Medications used 
 
 
 
 
 
 
 
Before 
Procedur
e 
1st hour 
Three weeks 
3 months 
NRS 
(Waist) 
 
 
 
 
 
 
 
 
NRS 
(Leg) 
 
 
 
 
 
 
 
 
CSI 
 
 
 
 
 
 
 
 
BDI 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
ODI 
 
 
 
 
 
 
 
 
PPT 
 
 
 
 
DN4