Effect of epidural polydeoxyribonucleotide in a rat model of lumbar foraminal stenosis

Background@#We aimed to investigate the effect of epidural polydeoxyribonucleotide (PDRN) on mechanical allodynia and motor dysfunction in a rat model of lumbar foraminal stenosis (LFS). @*Methods@#This study was conducted in two stages, using male Sprague-Dawley rats. The rats were randomly divided into eight groups. In the first stage, the groups were as follows: vehicle (V), sham (S), and epidural PDRN at 5 (P5), 8 (P8), and 10 (P10) mg/kg; and in the second stage, they were as follows: intraperitoneal PDRN 8 mg/kg, epidural 3,7-dimethyl-1-propargilxanthine (DMPX) (0.1 mg/kg), and DMPX (0.1 mg/kg). The LFS model was established, except for the S group. After an epidural injection of the test solutions, von Frey and treadmill tests were conducted for 3 weeks. Subsequently, histopathologic examinations were conducted in the V, S, P5, and P10 groups. @*Results@#A total of 65 rats were included. The P8 and P10 groups showed significant recovery from mechanical allodynia and motor dysfunction at all time points after drug administration compared to the V group. These effects were abolished by concomitant administration of DMPX. On histopathological examination, no epineurial inflammation or fibrosis was observed in the epidural PDRN groups. @*Conclusions@#Epidural injection of PDRN significantly improves mechanical allodynia and motor dysfunction in a rat model of LFS, which is mediated by the spinal adenosine A2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.

Effect of epidural polydeoxyribonucleotide in a rat model of lumbar foraminal stenosis

Background@#We aimed to investigate the effect of epidural polydeoxyribonucleotide (PDRN) on mechanical allodynia and motor dysfunction in a rat model of lumbar foraminal stenosis (LFS). @*Methods@#This study was conducted in two stages, using male Sprague-Dawley rats. The rats were randomly divided into eight groups. In the first stage, the groups were as follows: vehicle (V), sham (S), and epidural PDRN at 5 (P5), 8 (P8), and 10 (P10) mg/kg; and in the second stage, they were as follows: intraperitoneal PDRN 8 mg/kg, epidural 3,7-dimethyl-1-propargilxanthine (DMPX) (0.1 mg/kg), and DMPX (0.1 mg/kg). The LFS model was established, except for the S group. After an epidural injection of the test solutions, von Frey and treadmill tests were conducted for 3 weeks. Subsequently, histopathologic examinations were conducted in the V, S, P5, and P10 groups. @*Results@#A total of 65 rats were included. The P8 and P10 groups showed significant recovery from mechanical allodynia and motor dysfunction at all time points after drug administration compared to the V group. These effects were abolished by concomitant administration of DMPX. On histopathological examination, no epineurial inflammation or fibrosis was observed in the epidural PDRN groups. @*Conclusions@#Epidural injection of PDRN significantly improves mechanical allodynia and motor dysfunction in a rat model of LFS, which is mediated by the spinal adenosine A2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.

Recombinant zoster vaccine (Shingrix®): a new option for the prevention of herpes zoster and postherpetic neuralgia

Postherpetic neuralgia (PHN) is a challenging condition for pain management specialists. The prevention of herpes zoster (HZ) and subsequent PHN in individuals aged 50 years and older, via the development of new vaccines, is an ongoing research project. The live zoster vaccine (LZV, Zostavax®) was the first proof of concept that vaccination could prevent HZ, but LZV cannot be used in various immunecompromised patients. This led to the development of a new non-live recombinant zoster vaccine (RZV, Shingrix®). This RZV has shown promising results in many clinical trials, with high reactogenicity and similar systemic adverse effects compared to those of LZV. The National Advisory Committee on Immunization has recommended LZV as a standard vaccine for HZ prevention in adults ≥ 50 years of age, but no studies directly comparing the safety and efficacy of RZV and LZV vaccines have been conducted. This article reviews the brief history, efficacy, and safety of the two vaccines and discusses the advantage of RZV over LZV based on the available literature.

Radiation exposure to the eyes and thyroid during C-arm fluoroscopy-guided cervical epidural injections is far below the safety limit

Background@#The aim of this study was to evaluate radiation exposure to the eye and thyroid in pain physicians during the fluoroscopy-guided cervical epidural block (CEB). @*Methods@#Two pain physicians (a fellow and a professor) who regularly performed Carm fluoroscopy-guided CEBs were included. Seven dosimeters were used to measure radiation exposure, five of which were placed on the physician (forehead, inside and outside of the thyroid protector, and inside and outside of the lead apron) and two were used as controls. Patient age, sex, height, and weight were noted, as were radiation exposure time, absorbed radiation dose, and distance from the X-ray field center to the physician. @*Results@#One hundred CEB procedures using C-arm fluoroscopy were performed on comparable patients. Only the distance from the X-ray field center to the physician was significantly different between the two physicians (fellow: 37.5 ± 2.1 cm, professor: 41.2 ± 3.6 cm, P = 0.03). The use of lead-based protection effectively decreased the absorbed radiation dose by up to 35%. @*Conclusions@#Although there was no difference in radiation exposure between the professor and the fellow, there was a difference in the distance from the X-ray field during the CEBs. Further, radiation exposure can be minimized if proper protection (thyroid protector, leaded apron, and eyewear) is used, even if the distance between the X-ray beam and the pain physician is small. Damage from frequent, low-dose radiation exposure is not yet fully understood. Therefore, safety measures, including lead-based protection, should always be enforced.

Increased calcium-mediated cerebral processes after peripheral injury: possible role of the brain in complex regional pain syndrome

Background@#Among various diseases that accompany pain, complex regional pain syndrome (CRPS) is one of the most frustrating for patients and physicians. Recently, many studies have shown functional and anatomical abnormalities in the brains of patients with CRPS. The calcium-related signaling pathway is important in various physiologic processes via calmodulin (CaM) and calcium-calmodulin kinase 2 (CaMK2). To investigate the cerebral mechanism of CRPS, we measured changes in CaM and CaMK2 expression in the cerebrum in CRPS animal models. @*Methods@#The chronic post-ischemia pain model was employed for CRPS model generation. After generation of the animal models, the animals were categorized into three groups based on changes in the withdrawal threshold for the affected limb: CRPS-positive (P), CRPS-negative (N), and control (C) groups. Western blot analysis was performed to measure CaM and CaMK2 expression in the rat cerebrum. @*Results@#Animals with a decreased withdrawal threshold (group P) showed a significant increment in cerebral CaM and CaMK2 expression (P = 0.013 and P = 0.021, respectively). However, groups N and C showed no difference in CaM and CaMK2 expression. @*Conclusions@#The calcium-mediated cerebral process occurs after peripheral injury in CRPS, and there can be a relationship between the cerebrum and the pathogenesis of CRPS.

Topical agents: a thoughtful choice for multimodal analgesia / 대한마취과학회지

For over a thousand years, various substances have been applied to the skin to treat pain. Some of these substances have active ingredients that we still use today. However, some have been discontinued due to their harmful effect, while others have been long forgotten. Recent concerns regarding the cardiovascular and renal risk from nonsteroidal anti-inflammatory drugs, and issues with opioids, have resulted in increasing demand and attention to non-systemic topical alternatives. There is increasing evidence of the efficacy and safety of topical agents in pain control. Topical analgesics are great alternatives for pain management and are an essential part of multimodal analgesia. This review aims to describe essential aspects of topical drugs that physicians should consider in their practice as part of multimodal analgesia. This review describes the mechanism of popular topical analgesics and also introduces the most recently released and experimental topical medications.

Effectiveness of continuous hypertonic saline infusion with an automated infusion pump for decompressive neuroplasty: a randomized clinical trial / 대한통증학회지

BACKGROUND: Hypertonic saline (HS) injections for decompressive neuroplasty (DN) can cause pain. We assessed whether a continuous infusion of HS through an infusion pump would reduce injection-related pain compared with repeated bolus administrations. METHODS: Fifty patients scheduled for DN were randomized to either the bolus injection or the continuous infusion group. After appropriately placing the epidural catheter, 4 mL of 5% NaCl was injected as four boluses of 1 mL each at 15-minute intervals or infused over 1 hour using an infusion pump. The severity of pain induced by HS injection, as measured by the 11-point numerical rating scale (NRS), was the primary outcome. The severity of low back or lower extremity pain, as measured by the 11-point NRS and Oswestry Disability Index (ODI), 3 months following the procedure, was the secondary outcome. RESULTS: Data from 21 patients in the bolus group and 23 in the continuous infusion group were analyzed. No statistically significant difference in injection-related pain was identified between the two groups during the initial HS administration (P = 0.846). However, there was a statistically significant reduction in injection-related pain in the continuous infusion group compared to the bolus injection group from the second assessment onwards (P = 0.001, < 0.001, and < 0.001, respectively). No significant between-group differences in the NRS and ODI scores 3 months post-procedure were noted (P = 0.614 and 0.949, respectively). CONCLUSIONS: Our study suggests that administering HS through a continuous infusion is a useful modality for reducing HS injection-related pain during DN.

Prevalence of unrecognized depression in patients with chronic pain without a history of psychiatric diseases

BACKGROUND: We aimed to investigate the prevalence of unrecognized depression in patients with chronic pain, but with no history of psychiatric diseases. METHODS: Patients with chronic pain who did not have a history of psychiatric disease were selected for this study. The Beck Depression Index (BDI) was used to evaluate depression. Participants' socio-demographic characteristics and pain-related characteristics were also recorded. RESULTS: The study included 94 consecutive patients with chronic pain (28 men and 66 women). Based on the BDI scores, 33/94 (35.1%) patients with chronic pain had comorbid depression. The prevalence of depression was significantly higher in our cohort than it was in the general population (P < 0.001). The standardized incidence ratio, adjusted for age and sex, was 2.77 in men and 2.60 in women. Patients who were unmarried (odds ratio [OR] = 3.714, P = 0.044), and who had subjective sleep disturbance (OR = 8.885, P < 0.001), were more likely to have moderate to severe depression. Patients with high education levels (OR = 0.244, P = 0.016), and who were economically active (OR = 0.284, P = 0.023), were less likely to have moderate to severe depression. CONCLUSIONS: Our results indicate that unrecognized depression in patients with chronic pain is common. Therefore, pain physicians should actively seek to identify these problems rather than relying on the patient to volunteer such information.

Epiduroscopic Removal of a Lumbar Facet Joint Cyst

Facet joint synovial cysts are usually associated with osteoarthritis of the adjacent facet joint and/or spondylolisthesis. In between the conservative and operative ends of the treatment spectrum lie minimally invasive techniques such as cyst rupture using epiduroscopy. In this report, we describe an 82-year-old male patient presenting with low back pain radiating to his lower left extremity and associated paresthesia. Magnetic resonance imaging of the lumbar spine revealed a synovial cyst at left L4/5 facet joint. Using epiduroscopy, the cyst was mechanically ruptured by popping it with the tip of the scope. The patient remained symptom-free at his successive visits until 12 months after the procedure, and was opened for desired follow up.

Do Severity Score and Skin Temperature Asymmetry Correlate with the Subjective Pain Score in the Patients with Complex Regional Pain Syndrome? / 대한통증학회지

BACKGROUND: The diagnostic criteria of complex regional pain syndrome (CRPS) have mainly focused on dichotomous (yes/no) categorization, which makes it difficult to compare the inter-patient's condition and to evaluate the intra-patient's subtle severity over the course of time. To overcome this limitation, many efforts have been made to create laboratory methods or scoring systems to reflect the severity of CRPS; measurement of the skin temperature asymmetry is one of the former, and the CRPS severity score (CSS) is one of the latter. However, there has been no study on the correlations among the CSS, temperature asymmetry and subjective pain score. The purpose of this study was to evaluate whether there is any correlation between the CSS, skin temperature asymmetry and subjective pain score. METHODS: Patients affected with CRPS in a unilateral limb were included in this study. After making a diagnosis of CRPS according to the Budapest criteria, the CSS and skin temperature difference between the affected and unaffected limb (DeltaT) was measured in each patient. Finally, we conducted a correlation analysis among the CSS, DeltaT and visual analogue scale (VAS) score of the patients. RESULTS: A total of 42 patients were included in this study. There was no significant correlation between the DeltaT and VAS score (Spearman's rho = 0.066, P = 0.677). Also, the CSS and VAS score showed no significant correlation (Spearman's rho = 0.163, P = 0.303). CONCLUSIONS: The DeltaT and CSS do not seem to reflect the degree of subjective pain in CRPS patients.

Therapeutic Effect of Epidurally Administered Lipo-Prostaglandin E1 Agonist in a Rat Spinal Stenosis Model

BACKGROUND: A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. METHODS: A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, 0.15 microg.kg-1 of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of chromatolysis, chronic inflammation, and fibrosis in light microscopic images. RESULTS: From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less chromatolysis in the EP group than in the saline or control groups. CONCLUSIONS: An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.

Morphologic Diversities of Sacral Canal in Children; Three-Dimensional Computed Tomographic Study

BACKGROUND: Caudal block is a common technique in children for reducing postoperative pain, and there have been several reports on the variations of the sacral canal in children. However, previous studies have mainly focused on the needle trajectory for caudal block, and there is limited information on the structural variations of the sacrum in children. The purpose of this study was to analyze the anatomic variations of sacral canals in children. METHODS: Three-dimensional computed tomographic images were analyzed. The data from the images included fusion of the sacral vertebral laminae and the sacral intervertebral space existence of the sacral cornua and the types of sacral hiatus. The types of sacral hiatus were classified into 3 groups: group I (fusion of S3 or S4 vertebral laminae), group II (unfused vertebral arch with the distance of the S3 and S4 vertebral laminae or = 50% of the distance between the cornua). RESULTS: A total of 143 children were included in this study. All of the sacral vertebral arches were not fused in 22 children (15.4%). Cornua were not identified bilaterally in 5 (3.5%) and unilaterally in 6 (4.2%) children. In the sacral hiatus, group II and group III were identified in 22 (15.4%) and 31 (21.7%) children, respectively. CONCLUSIONS: The sacral canal has various anatomical variations in children. Careful attention must be paid to identify the correct anatomic landmark.

Do Severity Score and Skin Temperature Asymmetry Correlate with the Subjective Pain Score in the Patients with Complex Regional Pain Syndrome?

BACKGROUND: The diagnostic criteria of complex regional pain syndrome (CRPS) have mainly focused on dichotomous (yes/no) categorization, which makes it difficult to compare the inter-patient's condition and to evaluate the intra-patient's subtle severity over the course of time. To overcome this limitation, many efforts have been made to create laboratory methods or scoring systems to reflect the severity of CRPS; measurement of the skin temperature asymmetry is one of the former, and the CRPS severity score (CSS) is one of the latter. However, there has been no study on the correlations among the CSS, temperature asymmetry and subjective pain score. The purpose of this study was to evaluate whether there is any correlation between the CSS, skin temperature asymmetry and subjective pain score. METHODS: Patients affected with CRPS in a unilateral limb were included in this study. After making a diagnosis of CRPS according to the Budapest criteria, the CSS and skin temperature difference between the affected and unaffected limb (DeltaT) was measured in each patient. Finally, we conducted a correlation analysis among the CSS, DeltaT and visual analogue scale (VAS) score of the patients. RESULTS: A total of 42 patients were included in this study. There was no significant correlation between the DeltaT and VAS score (Spearman's rho = 0.066, P = 0.677). Also, the CSS and VAS score showed no significant correlation (Spearman's rho = 0.163, P = 0.303). CONCLUSIONS: The DeltaT and CSS do not seem to reflect the degree of subjective pain in CRPS patients.

Anatomic Characteristics of Supraorbital Foramina in Korean Using Three-Dimensional Model

BACKGROUND: The aims of this study were to analyze the anatomic variations of supraorbital foramina/notches in Koreans and to compare the results with those of previous studies examining other races. We evaluated the three-dimensional computed tomography (3D-CT) images of human faces using multidetector computed tomography (MDCT). METHODS: A total of 395 adults (232 men and 163 women) were enrolled and the 3D-CT images of their faces were reviewed in this study. In this study, the data from the images included the presence, shape, width and distance from the nasion to the supraorbital foramina/notches. ANOVA was used to assess the main effects of gender and side (right or left foramen/notch), and comparisons of the means were done by paired t-test. RESULTS: The most common shapes in Koreans were a single notch (39.5%) on the right hand side and a single foramen (42.3%) on the left hand side. The incidence of a single foramen in Koreans was high compared to other races. The mean foramen diameter was 2.34 +/- 0.78 mm, and the mean distance from the nasion was 27.19 +/- 4.03 mm. The mean notch diameter was 3.37 +/- 1.71 mm, and the mean distance from the nasion was 23.42 +/- 2.45 mm. CONCLUSIONS: This is the first study on the variations of supraorbital foramina/notches in Koreans using 3D-CT images of faces. The anatomic characteristics of the supraorbital foramina/notch will help in performing nerve blocks and maxillofacial surgery.

Efficacy of Intra-articular Steroid Injection in Patients with Femoroacetabular Impingement

Femoroacetabular Impingement (FAI) arises from morphological abnormalities between the proximal femur and acetabulum. Impingement caused by these morphologic abnormalities induces early degenerative changes in the hip joint. Furthermore, FAI patients complain of severe pain and limited range of motion in the hip, but a guideline for treatment of FAI has not yet been established. Medication, supportive physical treatment and surgical procedures have been used in the treatment of the FAI patients; however, the efficacies of these treatments have been limited. Here, we report the diagnosis and treatment for 3 cases of FAI patients. Intra-articular (IA) steroid injection of the hip joint was performed in all three patients. After IA injection, pain was reduced and function had improved for up to three months.

Evaluation of the neurological safety of epidurally-administered pregabalin in rats / 대한마취과학회지

BACKGROUND: The primary site of action of pregabalin, i.e. the alpha-2-delta subunit of the voltage-dependent calcium channel, is located at the dorsal root ganglion and dorsal horn of the spinal cord. Therefore, the epidural administration of pregabalin could have advantages over oral administration. However, the possibility of its neurotoxicity should be excluded before any attempt at epidural administration. We evaluated the neuronal safety of epidurally-administered pregabalin by observing the sensory/motor changes and examining the histopathology of spinal cord in rats. METHODS: Sixty rats of 180-230 g were divided into three groups; 3 mg of pregabalin dissolved in 0.3 ml saline (group P, n = 20), 0.3 ml 40% alcohol (group A, n = 20), or 0.3 ml normal saline (group N, n = 20) was administered epidurally to the rats in each group. Pinch-toe test, motor function evaluation, and histopathologic examination of vacuolation, chromatolysis, meningeal inflammation, and neuritis were performed at the 1st, 3rd, 7th, and 21st day after each epidural administration. RESULTS: All rats enrolled in group P, like those in group N, showed neither sensory/motor dysfunction nor any histopathological abnormality over the 3-week observation period. In contrast, in group A, 80% of the rats showed abnormal response to the pinch-toe test and all rats showed decreased motor function during the entire evaluation period. In addition, all histopathologic findings of neurotoxicity were observed exclusively in group A. CONCLUSIONS: The epidurally administered pregabalin (about 15 mg/kg) did not cause any neurotoxic evidence, in terms of both sensory/motor function evaluation and histopathological examination in rats.

Unilateral, Single Needle Approach Using an Epidural Catheter for Bilateral Superior Hypogastric Plexus Block

The superior hypogastric plexus block (SHPB) is used for treating pelvic pain, especially in patients with gynecological malignancies. Various approaches to this procedure have been reported due to the anatomic obstacles of a high iliac crest or large transverse process of the 5th lumbar vertebra. Here, we report a new technique of superior hypogastric plexus block using a unilateral single-needle approach to block the bilateral superior hypogastric plexus with a Tuohy needle and epidural catheter. We have confidence that this new technique can be another option in performing the SHPB when the conventional bilateral approach is difficult to perform.

Catheter Obstruction of Intrathecal Drug Administration System: A Case Report

Intrathecal drug administration system (ITDAS) can reduce the side effects while increasing the effectiveness of opioids compared to systemic opioid administration. Therefore, the use of ITDAS has increased in the management of cancer pain and chronic intractable pain. Catheter obstruction is a serious complication of ITDAS. Here, we present a case of catheter obstruction by a mass formed at the side hole and in the lumen. A 37-year-old man suffering from failed back surgery syndrome received an ITDAS implantation, and the ITDAS was refilled with morphine every 3 months. When the patient visited the hospital 18 months after ITDAS implantation for a refill, the amount of delivered morphine sulfate was much less than expected. Movement of the pump rotor was examined with fluoroscopy; however, it was normal. CSF aspiration through the catheter access port was impossible. When the intrathecal catheter was removed, we observed that the side hole and lumen of the catheter was plugged.

Pulsed Radiofrequency Lesioning of the Axillary and Suprascapular Nerve in Calcific Tendinitis

The patient was a 45-year-female who presented with pain at right shoulder and right upper arm. The patient suffered from right shoulder and arm pain for 3 years and had pain management which was performed using medication and conservative management after she had been diagnosed with calcific tendinitis. However, substantial pain relief was not consistently achieved, and recurrence of pain was reported. Therefore, we performed right axillary nerve and suprascapular nerve block through pulsed radiofrequency. Two months after the procedure, the shoulder pain gradually subsided with the size reduction of the calcified nodule and she needed no more pain management.

Psychometric Characteristics of the Korean Version of the Roland-Morris Disability Questionnaire

The aims of this study were; 1) to develop the final version of the Korean Roland-Morris Disability Questionnaire (RDQ), and 2) to compare the responsiveness between the RDQ and the Oswestry Disability Index (ODI) scores in patients having low back pain. The psychometric properties of the final Korean RDQ were evaluated in 221 patients. Among them, 30 patients were reliability tested. Validity was evaluated using an 11-point numerical rating scale (NRS) and the Korean ODI. The receiver operating characteristic (ROC) curve analysis of the RDQ and the ODI was compared in 54 patients with lumbar zygapophyseal (facet) joint pain. There was a moderate relationship between the RDQ and NRS (r = 0.59, P < 0.01) and a strongly positive correlation between the RDQ and the ODI (r = 0.76, P < 0.001). The Korean RDQ with the higher area under the ROC curve showed a better overall responsive performance than did the ODI in patients with lumbar facet joint pain after medial branch radiofrequency neurotomy (P < 0.01). The results of the study present the final version of the Korean RDQ is valid for assessing functional status in a Korean population with chronic low back pain.