The effect of human mesenchymal stem cell injection on pain behavior in chronic post-ischemia pain mice

Background@#Neuropathic pain (NP) is considered a clinically incurable condition despite various treatment options due to its diverse causes and complicated disease mechanisms. Since the early 2000s, multipotent human mesenchymal stem cells (hMSCs) have been used in the treatment of NP in animal models. However, the effects of hMSC injections have not been studied in chronic post-ischemia pain (CPIP) mice models. Here, we investigated whether intrathecal (IT) and intrapaw (IP) injections of hMSCs can reduce mechanical allodynia in CPIP model mice. @*Methods@#Seventeen CPIP C57/BL6 mice were selected and randomized into four groups: IT sham (n = 4), IT stem (n = 5), IP sham (n = 4), and IP stem (n = 4). Mice in the IT sham and IT stem groups received an injection of 5 μL saline and 2 × 104 hMSCs, respectively, while mice in the IP sham and IP stem groups received an injection of 5 μL saline and 2 × 10 5 hMSCs, respectively. Mechanical allodynia was assessed using von Frey filaments from pre-injection to 30 days post-injection. Glial fibrillary acidic protein (GFAP) expression in the spinal cord and dorsal root ganglia were also evaluated. @*Results@#IT and IP injections of hMSCs improved mechanical allodynia. GFAP expression was decreased on day 25 post-injection compared with the sham group. Injections of hMSCs improved allodynia and GFAP expression was decreased compared with the sham group. @*Conclusions@#These results suggested that hMSCs may be also another treatment modality in NP model by ischemia-reperfusion.

Anti-Allodynic Effects of Polydeoxyribonucleotide in an Animal Model of Neuropathic Pain and Complex Regional Pain Syndrome

Background@#Spinal nerve ligation (SNL) model is one of the representative models of the neuropathic pain model. Neuropathic pain in a chronic post-ischemic pain (CPIP) mimics the symptoms of complex regional pain syndrome (CRPS). The administration of polydeoxyribonucleotide (PDRN), which has regenerative and anti-inflammatory effects, has been studied and is used in clinical practice treating various diseases. However, the analgesic effect of PDRN in a neuropathic pain or CRPS model remains unknown. @*Methods@#PDRN (3.3, 10, and 20 mg/kg) was administered into the subcutaneous (SC) layer of the hind paws of SNL and CPIP models. Mechanical anti-allodynic effects were then investigated using the von Frey test. In the immunohistochemical examination, dorsal root ganglia (DRG) and the spinal cord were harvested and examined for the expression of glial fibrillary acidic protein (GFAP) after the 20 mg PDRN injection. @*Results@#Mechanical allodynia was significantly alleviated by administration of PDRN in SNL and CPIP mice at all of the time point. As the dose of PDRN increased, the effect was greater. The 20 mg PDRN injection was found to have the most effective anti-allodynic effect. The increased expression of GFAP in DRG and the spinal cord of SNL and CPIP model decreased following the administration of PDRN than vehicle. @*Conclusion@#SC administration of PDRN results in the attenuation of allodynia and activation of astrocytes in neuropathic pain or CRPS models. We propose that PDRN can have significant potential advantages in neuropathic pain treatment.

Analgesic effects of soluble epoxide hydrolase inhibitor in K/BxN serum transfer arthritis mouse model

BACKGROUND: Soluble epoxide hydrolase (sEH) is an enzyme that converts epoxyeicosatrienoic acid (EET) into the anti-inflammatory dihydroxyeicosatrienoic acids (DHET). Inhibition of sEH by the potent soluble epoxide hydrolase inhibitor (sEHI) decreases inflammation by increasing EET. The K/BxN serum transfer mouse model of arthritis displays an initial inflammation and an associated tactile allodynia that continues on following the resolution of inflammation. METHODS: We undertook the following studies: i) Using the K/BxN mouse model, we examined effects on allodynia during the early inflammatory phase of administration of sEHI 3 mg/kg and/or diclofenac (DFC) 10 mg/kg. ii) In the late inflammatory phase, we administered sEHI (3, 10, or 30 mg/kg); DFC 10 mg/kg; gabapentin 100 mg/kg. iii) Using the conditioned place preference (CPP) we examined the synergism between sEHI and DFC in the K/BxN mouse using the CPP paradigm. The drug was administered intraperitoneally and the allodynia was measured with the von Frey test. RESULTS: In the early phase, both sEHI and DFC displayed an antiallodynic action. In the late phase, sEHI, and gabapentin but not DFC were effective in reversing the allodynia. Comparable results were observed with the CPP. CONCLUSIONS: This study demonstrates that sEHI reduces mechanical allodynia in both the early and the late inflammatory K/BxN mouse model of arthritis. The sEHI target thus addresses the hyperalgesia arising from inflammation as well as the post-inflammatory phase that has been said to reflect neuropathic-like states, thus presenting alternatives to the limited efficacy of arthritis drugs in use.

Guidelines for prescribing opioids for chronic non-cancer pain in Korea

As the treatment of chronic non-cancer pain gradually increases, clinicians have more opportunities to encounter opioid prescription. However, guidelines for prescribing opioids for chronic non-cancer pain have never been published in Korea. The present guidelines were prepared by reviewing various research data. In cases in which the data were insufficient, recommendations were presented following discussion among experts affiliated with the Opioids Research Group in the Korean Pain Society. The present guidelines may need to be continuously revised and amended as more clinical evidence is acquired.

Ultrasound-guided pararadicular block using a paramedian sagittal oblique approach for managing low back pain in a pregnant woman: A case report

Lumbar radicular pain is conventionally treated with transforaminal epidural injection under the guidance of fluoroscopy or computer tomography. However, fluoroscopic radiation can be hazardous in certain populations, including pregnant women. An adjustment of the amount of local anesthetic is required in this population. An alternative method of lumbar root block using ultrasound (US) guidance has recently been introduced. Here, we present the case of a pregnant woman with worsening lumbar radicular pain during her pregnancy and the management of her pain using US-guided pararadicular block.

A sheared Racz catheter in cervical epidural space for thirty months: a case report / 대한마취과학회지

Percutaneous epidural neuroplasty may lead to complications such as hematoma, infection, epidural abscess, meningitis, hypotension, respiratory depression, urinary and fecal dysfunction, sexual dysfunction and paresthesia. Other technical complications may include shearing or tearing, misplacement, blockage and migration of the catheter. We report a case of a 41-year-old female patient, who underwent surgical removal of a sheared catheter, which was retained for 30 months after cervical Racz neuroplasty.

Ultrasound-guided pudendal nerve pulsed radiofrequency in patients with refractory pudendal neuralgia: Three cases report

Pudendal neuralgia is characterized by severe sharp pain along the innervation area of pudendal nerve, which may be worsened when sitting position. Successful pudendal nerve block is crucial to the diagnosis of pudendal neuralgia. Although fluoroscopy-guided pudendal nerve blocks have traditionally been performed, recently ultrasound-guided pudendal nerve blocks were reported. For the long term effect of nerve block, pulsed radiofrequency was performed under fluoroscopic guidance in some reports. We report our successful experiences of three cases using ultrasound-guided pulsed radiofrequency.

Ultrasound-guided pulsed radiofrequency treatment for postherpetic neuralgia of supraorbital nerve: A case report

Pulsed radiofrequency treatment has an analgesic effect by neuromodulation of the central pain pathway without neural injury. However, lack of knowledge regarding the exact mechanism on neuropathic pain makes the use of pulsed radiofrequency treatment controversial. Here, we describe a case of satisfactory pain relief after ultrasound-guided pulsed radiofrequency treatment in a patient with supraorbital herpetic pain refractory to medication. This case indicates the potential of ultrasound-guided pulsed radiofrequency treatment in patients with postherpetic supraorbital neuralgia.

Chemotherapy induced peripheral neuropathic pain / 대한마취과학회지

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most serious complications associated with anticancer drugs. CIPN leads to a lower quality of life and dysfunction of the sensory, motor, and autonomic systems, and often causes patients to discontinue chemotherapy. It is usually misdiagnosed and undertreated due to a lack of consensus and unclear pathophysiology, for which many mechanisms have been suggested, including mitochondrial dysfunction, various pain mediators, abnormal spontaneous discharge in A and C fibers, and others. To date, no agents have been shown to effectively prevent CIPN, leading to debate as to the standard protocol. Duloxetine has demonstrated a moderate therapeutic effect against CIPN. Although tricyclic antidepressants (such as nortriptyline or desipramine), gabapentin, and a topical gel containing baclofen (10 mg), amitriptyline HCL (40 mg), and ketamine (20 mg) showed inconclusive results in CIPN trials, these agents are currently considered the best options for CIPN treatment. Therefore, further studies on the pathophysiology and treatment of CIPN are needed.

Anti-Allodynic Effects of Levodopa in Neuropathic Rats

PURPOSE: Levodopa is the most effective anti-Parkinsonian agent. It has also been known to exhibit analgesic properties in laboratory and clinical settings. However, studies evaluating its effects on neuropathic pain are limited. The aim of the present study was to examine the anti-allodynic effects of levodopa in neuropathic rats. MATERIALS AND METHODS: Sprague-Dawley male rats underwent the surgical procedure for L5 and L6 spinal nerves ligation. Sixty neuropathic rats were randomly divided into 6 groups for the oral administration of distilled water and levodopa at 10, 30, 50, 70, and 100 mg/kg, respectively. We co-administered carbidopa with levodopa to prevent peripheral synthesis of dopamine from levodopa, and observed tactile, cold, and heat allodynia pre-administration, and at 15, 30, 60, 90, 120, 150, 180, and 240 min after drug administration. We also measured locomotor function of neuropathic rats using rotarod test to examine whether levodopa caused side effects or not. RESULTS: Distilled water group didn't show any difference in all allodynia. For the levodopa groups (10-100 mg/kg), tactile and heat withdrawal thresholds were increased, and cold withdrawal frequency was decreased dose-dependently (p0.05). CONCLUSION: Levodopa reversed tactile, cold and heat allodynia in neuropathic rat without any side effects.

Analgesic Effects of Dexmedetomidine in Vincristine-Evoked Painful Neuropathic Rats

Dexmedetomidine, which is a selective alpha2-adrenoceptor agonist, was recently introduced into clinical practice for its analgesic properties. The purpose of this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2 weeks. Saline and dexmedetomidine (12.5, 25, 50, and 100 microg/kg) were injected to rats developed allodynia 14 days after vincristine injection, respectively. We evaluated allodynia at before, 15, 30, 60, 90, 120, 180, and 240 min, and 24 hr after intraperitoneal drug (normal saline or dexmedetomidine) injection. Saline treatment did not show any differences for all the allodynia. Maximal paw withdrawal thresholds to mechanical stimuli were 3.0 +/- 0.4, 9.1 +/- 1.9, 13.0 +/- 3.6, 16.6 +/- 2.4, and 24.4 +/- 1.6 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold stimuli were 73.3 +/- 4.2, 57.1 +/- 6.8, 34.3 +/- 5.7, 20.0 +/- 6.2, and 14.3 +/- 9.5 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P < 0.05).

Analgesic Effects of Dexmedetomidine in Vincristine-Evoked Painful Neuropathic Rats

Dexmedetomidine, which is a selective alpha2-adrenoceptor agonist, was recently introduced into clinical practice for its analgesic properties. The purpose of this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2 weeks. Saline and dexmedetomidine (12.5, 25, 50, and 100 microg/kg) were injected to rats developed allodynia 14 days after vincristine injection, respectively. We evaluated allodynia at before, 15, 30, 60, 90, 120, 180, and 240 min, and 24 hr after intraperitoneal drug (normal saline or dexmedetomidine) injection. Saline treatment did not show any differences for all the allodynia. Maximal paw withdrawal thresholds to mechanical stimuli were 3.0 +/- 0.4, 9.1 +/- 1.9, 13.0 +/- 3.6, 16.6 +/- 2.4, and 24.4 +/- 1.6 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold stimuli were 73.3 +/- 4.2, 57.1 +/- 6.8, 34.3 +/- 5.7, 20.0 +/- 6.2, and 14.3 +/- 9.5 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P < 0.05).

Sacral Nerve Stimulation for Treatment of Chronic Intractable Anorectal Pain: A Case Report

Despite recent methodological advancement of the practical pain medicine, many cases of the chronic anorectal pain have been intractable. A 54-year-old female patient who had a month history of a constant severe anorectal pain was referred to our clinic for further management. No organic or functional pathology was found. In spite of several modalities of management, such as medications and nerve blocks had been applied, the efficacy of such treatments was not long-lasting. Eventually, she underwent temporary then subsequent permanent sacral nerve stimulation. Her sequential numerical rating scale for pain and pain disability index were markedly improved. We report a successful management of the chronic intractable anorectal pain via permanent sacral nerve stimulation. But further controlled studies may be needed.

Ganglion Impar Block With Botulinum Toxin Type A for Chronic Perineal Pain -A Case Report-

Chronic perineal pain is an often encountered problem, which produces a great degree of functional impairment and frustration to the patient and a challenge to the treating physician. The reason for this problem is that the region contains diverse anatomic structures with mixed somatic, visceral and autonomic innervations affecting bladder and bowel control and sexual function. A blockade of nociceptive and sympathetic supply to the perineal region, supplied through the ganglion impar has been shown to benefit patients with chronic perineal pain. Several options to this block have been described that chemical neurolysis, radiofrequency ablation etc. Although the analgesic effect of Botulinum toxin type A (BoNT-A) has long been considered secondary to its action for muscle relaxation, BoNT-A also affects the release of the neurotransmitters that are involved in pain perception. We describe a patient who was successfully given ganglion impar block with BoNT-A.

Pharmacologic Management of Chronic Pain

Chronic pain is a multifactorial condition with both physical and psychological symptoms, and it affects around 20% of the population in the developed world. In spite of outstanding advances in pain management over the past decades, chronic pain remains a significant problem. This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel alpha2-delta ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment.

Effect of remifentanil on tumor necrosis factor-alpha and interleukin-6 responses in patients undergoing laparoscopic hysterectomy

BACKGROUND: Cytokines are important mediators of immune response to surgery and pain.The aim of the study was to investigate the effect of remifentanil on serum levels of cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), in patients undergoing laparoscopic hysterectomy. METHODS: Twenty four patients scheduled for laparoscopic hysterectomy were randomly assigned to control or remifentanil group.Both groups received 1.5-2.5% end tidal concentration of sevoflurane and air in 50% oxygen.Remifentanil group received a bolus of remifentanil 1microgram/kg over 1 min and an infusion of remifentanil at a rate of 0.1microgram/kg/min.Control group received 10 ml saline (placebo) and an infusion of saline at the same rate. Venous blood samples for measurement of serum cytokine concentrations were taken before anesthesia (T1), at 2 h after infusion (T2), and at the 1 hour after surgery (T3). RESULTS: Serum TNF-alpha concentration did not differ significantly over time in both groups.Serum TNF-alpha concentration was higher in remifentanil group at T3 (9.76 +/- 1.19 pg/ml vs.8.53 +/- 0.71 pg/ml) than in control group (P < 0.05). In both groups, serum IL-6 concentrations were significantly higher at T3, when compared to those at T1 and T2 (P < 0.05). CONCLUSIONS: Remifentanil did not attenuate early postoperative change of serum TNF-alpha and IL-6 concentrations in patients undergoing laparoscopic hysterectomy. Serum IL-6 level increased at postoperative 1 h, regardless of remifentanil use.

The effects of callander modification of laryngoscopic blade on hemodynamic changes according to the degree of difficult airway / 대한마취과학회지

BACKGROUND: Laryngoscopy and tracheal intubation are known to have profound cardiovascular effects. The Callander modification of Macintosh blade is associated with greater field of laryngoscopic view and decreased risk of dental contact. The purpose of this study was to compare the hemodynamic responses to laryngoscopy and tracheal intubation according to the degree of difficult airway, and to evaluate the usefulness of Callander modification of Macintosh blade for attenuating the hemodynamic responses. METHODS: One hundred, forty-eight patients scheduled for elective surgery were divided into Easy group and Difficult group by Wilson's risk sum score. Laryngoscopy was performed using either an ordinary Macintosh No. 3 blade or the modified Macintosh blade. The modification consisted of reducing the height of the flange by partial removal, as described by Callander et al. Hemodynamic variables (systolic, diastolic, mean blood pressure, heart rate and rate pressure product) were noted before induction (baseline) and immediately after intubation. RESULTS: The hemodynamic changes after tracheal intubation in Difficult group were significantly greater than those in Easy group (P < 0.05). When using the modified blade, systolic, diastolic and mean blood pressure after tracheal intubation were lower than those using the conventional blade regardless of Wilson's risk sum score, but no statistical significances could be found. CONCLUSIONS: The hemodynamic changes after tracheal intubation increased as the degree of airway difficulty increased. Laryngoscopy with the Callander's modified blade did not reduce the degree of hemodynamic stimulation compared with the conventional Macintosh blade.

Assessment for the Quality of Recovery from General Anesthesia in Patients with Gynecologic Surgery / 대한마취과학회지

BACKGROUND: Quality of recovery, assessed by patients, is related to patients' satisfaction, and even to quality of life. Of numerous patient-based measures to evaluate the quality of recovery, a '40-item-quality of recovery (QoR-40)' has proved to be valid and reliable. Using this questionnaire, we evaluated the quality of recovery in the gynecological patients and tried to identify factors affecting the quality of recovery. METHODS: Patients undergoing gynecological surgery were asked to fill a questionnaire 8 to 9 p.m the day after the completion of anesthesia. Questionnaires were prepared after translation to Korean from 40-item-quality of recovery. From the anesthetic and recovery room records we collected data about patient's age, surgery types, anesthetic and surgical duration, recovery room stay, main anesthetic agents, and recovery room complications. RESULTS: A total of 383 patients completed the questionnaires. Patients aged under 40 got significantly lower QoR-40 scores than those aged over 40, especially in the dimension of pain (P < 0.05). Patients who had undergone laparoscopic surgery got higher scores than those had undergone non-laparoscopic surgery (P < 0.05). Patients who answered the questionnaires in more than 30 hours after the completion of anesthesia showed lower total scores than those who did in less than 30 hours, especially in the dimensions of emotional state and pain (P < 0.05). CONCLUSIONS: In gynecological patients, laparoscopic surgery improved quality of recovery. Quality of recovery was affected by age and survey time. Postoperative pain contributed to the decrease of the quality of recovery.

The Analgesic Efficacy of a 5% Eutectic Mixture of Lidocaine and Prilocaine Prior to Insertion of Spinal and Epidural Block / 대한마취과학회지

BACKGROUND: We evaluated the analgesic efficacy of a 5% eutectic mixture of lidocaine and prilocaine (EMLA(R)) topically applied before performing skin puncture for spinal or epidural anesthesia. METHODS: The patient population consisted of 75 ASA physical status 1 and 2 adults scheduled for operations of the lower abdominal region, the perineal region or the lower extremities. The patients were randomly allocated to one of five groups of equal size: group A - topical application of EMLA(R) cream 120 min before spinal block; group B - subcutaneous infiltrationof 2 ml of 2% lidocaine immediately before spinal block; group C - no pretreatment before spinal block; group D - topical application of EMLA(R) cream 120 min before epidural block; and group E - subcutaneous infiltration of 2 ml of 2% lidocaine immediatelybefore epidural block. Pain experienced during the whole procedure was rated using a 10 cm visual analogue scale. RESULTS: Patients in group A experienced less pain compared with those in groups B and C (2.0 +/- 1.9 cm vs 4.1 +/- 1.9 cm and 3.9 +/- 2.2 cm, respectively; P < 0.05). However there was no significant difference between group D and group E (3.6 +/- 2.4 cm vs 4.1 +/- 2.5 cm). The patients in group A and group D were highly satisfied with the method of analgesia (P < 0.05). CONCLUSIONS: EMLA(R) cream is an effective alternative to subcutaneous infiltration of local anesthetic for analgesia during skin puncture using a 25 G spinal needle. It provides insufficient analgesia however for epidural anesthesia.

C-arm guided placement of Fogarty embolectomy catheter for one lung ventilation in an infant: A case report / 대한마취과학회지

We experienced one lung anesthesia using Fogarty embolectomy catheter as a bronchial blocker in an infant undergoing thoracotomy for foreign body removal. For the guidance of catheter placement in left mainstem bronchus, C-arm fluoroscopy was used. Size of catheter and its balloon was decided beforehand by measuring the diameter and length of bronchus based on the view obtained from computerized tomography. There was no accidental episode during anesthesia. C-arm fluoroscopy is safe and useful method to decide the position of Fogarty occlusion catheter in an infant.