SARS‑CoV‑2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID‑19 model / 한국실험동물학회지

Background@#The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. @*Results@#K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. @*Conclusion@#Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Laboratory information management system for COVID-19 non-clinical efficacy trial data / 한국실험동물학회지

Background@#As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. @*Results@#In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. @*Conclusions@#This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Relationship between paravertebral muscle twitching and long-term effects of radiofrequency medial branch neurotomy

BACKGROUND: To achieve a prolonged therapeutic effect in patients with lumbar facet joint syndrome, radiofrequency medial branch neurotomy (RF-MB) is commonly performed. The purpose of this study was to evaluate the prognostic value of paravertebral muscle twitching when performing RF-MB in patients with lumbar facet joint syndrome. METHODS: We collected and analyzed data from 68 patients with confirmed facet joint syndrome. Sensory stimulation was performed at 50 Hz with a 0.5 V cut-off value. Patients were divided into 3 groups according to the twitching of the paravertebral muscle during 2 Hz motor stimulation: ‘Complete’, when twitching was observed at all needles; ‘Partial’, when twitching was present at 1 or 2 needles; and ‘None’, when no twitching was observed. The relationship between the long-term effects of RF-MB and paravertebral muscle twitching was analyzed. RESULTS: The mean effect duration of RF-MB was 4.6, 5.8, and 7.0 months in the None, Partial, and Complete groups, respectively (P = 0.47). Although the mean effect duration of RF-MB did not increase significantly in proportion to the paravertebral muscle twitching, the Complete group had prolonged effect duration (> 6 months) than the None group in subgroup analysis. (P = 0.03). CONCLUSIONS: Paravertebral muscle twitching while performing lumbar RF-MB may be a reliable predictor of long-term efficacy when sensory provocation under 0.5 V is achieved. However, further investigation may be necessary for clarifying its clinical significance.

Clinical Identification of the Vertebral Level at Which the Lumbar Sympathetic Ganglia Aggregate

BACKGROUND: The location and the number of lumbar sympathetic ganglia (LSG) vary between individuals. The aim of this study was to determine the appropriate level for a lumbar sympathetic ganglion block (LSGB), corresponding to the level at which the LSG principally aggregate. METHODS: Seventy-four consecutive subjects, including 31 women and 31 men, underwent LSGB either on the left (n = 31) or the right side (n = 43). The primary site of needle entry was randomly selected at the L3 or L4 vertebra. A total of less than 1 ml of radio opaque dye with 4% lidocaine was injected, taking caution not to traverse beyond the level of one vertebral body. The procedure was considered responsive when the skin temperature increased by more than 1℃ within 5 minutes. RESULTS: The median responsive level was significantly different between the left (lower third of the L4 body) and right (lower margin of the L3 body) sides (P = 0.021). However, there was no significant difference in the values between men and women. The overall median responsive level was the upper third of the L4 body. The mean responsive level did not correlate with height or BMI. There were no complications on short-term follow-up. CONCLUSIONS: Selection of the primary target in the left lower third of the L4 vertebral body and the right lower margin of the L3 vertebral body may reduce the number of needle insertions and the volume of agents used in conventional or neurolytic LSGB and radiofrequency thermocoagulation.

Cross-cultural Adaptation and Linguistic Validation of the Korean Version of the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale

Distinction between neuropathic pain and nociceptive pain helps facilitate appropriate management of pain; however, diagnosis of neuropathic pain remains a challenge. The aim of this study was to develop a Korean version of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale and assess its reliability and validity. The translation and cross-cultural adaptation of the original LANSS pain scale into Korean was established according to the published guidelines. The Korean version of the LANSS pain scale was applied to a total of 213 patients who were expertly diagnosed with neuropathic (n = 113) or nociceptive pain (n = 100). The Korean version of the scale had good reliability (Cronbach's alpha coefficient = 0.815, Guttman split-half coefficient = 0.800). The area under the receiver operating characteristic curve was 0.928 with a 95% confidence interval of 0.885-0.959 (P or = 12, sensitivity was 72.6%, specificity was 98.0%, and the positive and negative predictive values were 98% and 76%, respectively. The Korean version of the LANSS pain scale is a useful, reliable, and valid instrument for screening neuropathic pain from nociceptive pain.

Alternative Method of Retrocrural Approach during Celiac Plexus Block Using a Bent Tip Needle

BACKGROUND: This study sought to determine safe ranges of oblique angle, skin entry point and needle length by reviewing computed tomography (CT) scans and to evaluate the usefulness of a bent tip needle during celiac plexus block (CPB). METHODS: CT scans of 60 CPB patients were reviewed. Image of the uppermost margin of L2 vertebral body was used to measure the minimal and maximal oblique angles and the distances from the midline to skin puncture point. The imaginary needle trajectory distance was calculated by three-dimensional measurement. When the procedure was performed by using a 10degrees bent tip needle under a 20degrees oblique X-ray fluoroscopic view, the distance (GF/G'F) from the midline to the actual puncture site was measured. RESULTS: The imaginary safe oblique angle range was 26.4-34.2degrees and 27.7-36.0degrees on the right and left, respectively. The distance from the midline to skin puncture point was 6.1-7.6 cm on the right and 6.3-7.6 cm on the left. The needle trajectory distance at minimal angle was 9.6-11.6 cm on the right and 9.5-11.5 cm on the left. The distance of GF/G'F was 5.1-6.5 cm and 5.0-6.4 cm on the right and left, respectively. All imaginary parameters were correlated with BMI except for GF/G'F. All complications were mild and transient. CONCLUSIONS: We identified safe values of angles and distances using a straight needle. Furthermore, using a bent tip needle under a 20degrees oblique fluoroscopic view, we could safely perform CPB with smaller parameter values.

Incidence and Risk Factors of Postoperative Nausea and Vomiting in Patients with Fentanyl-Based Intravenous Patient-Controlled Analgesia and Single Antiemetic Prophylaxis

PURPOSE: We evaluated the incidence and risk factors of postoperative nausea and vomiting (PONV) in patients with fentanyl-based intravenous patient-controlled analgesia (IV-PCA) and single antiemetic prophylaxis of 5-hydroxytryptamine type 3 (5 HT3)-receptor antagonist after the general anesthesia. MATERIALS AND METHODS: In this retrospective study, incidence and risk factors for PONV were evaluated with fentanyl IV-PCA during postoperative 48 hours after various surgeries. RESULTS: Four hundred-forty patients (23%) of 1878 had showed PONV. PCA was discontinued temporarily in 268 patients (14%), mostly due to PONV (88% of 268 patients). In multivariate analysis, female, non-smoker, history of motion sickness or PONV, long duration of anesthesia (>180 min), use of desflurane and intraoperative remifentanil infusion were independent risk factors for PONV. If one, two, three, four, five, or six of these risk factors were present, the incidences of PONV were 18%, 19%, 22%, 31%, 42%, or 50%. Laparoscopic surgery and higher dose of fentanyl were not risk factors for PONV. CONCLUSION: Despite antiemetic prophylaxis with 5 HT3-receptor antagonist, 23% of patients with fentanyl-based IV-PCA after general anesthesia showed PONV. Long duration of anesthesia and use of desflurane were identified as risk factors, in addition to risk factors of Apfel's score (female, non-smoker, history of motion sickness or PONV). Also, intraoperative remifentanil infusion was risk factor independent of postoperative opioid use. As the incidence of PONV was up to 50% according to the number of risk factors, risk-adapted, multimodal or combination therapy should be applied.

Survey on the Treatment of Postherpetic Neuralgia in Korea; Multicenter Study of 1,414 Patients

BACKGROUND: Postherpetic neuralgia (PHN) is a serious complication resulting from herpes zoster infections, and it can impair the quality of life. In order to relieve pain from PHN, various treatments, including pharmacological and interventional methods have been used. However, little information on the recommendations for the interventional treatment of PHN, along with a lack of nation-wide surveys on the current status of PHN treatment exists. This multicenter study is the first survey on the treatment status of PHN in Korea. METHODS: Retrospective chart reviews were conducted on the entire patients who visited the pain clinics of 11 teaching hospitals from January to December of 2011. Co-morbid disease, affected site of PHN, routes to pain clinic visits, parenteral/topical medications for treatment, drugs used for nerve block, types and frequency of nerve blocks were investigated. RESULTS: A total of 1,414 patients' medical records were reviewed. The most commonly affected site was the thoracic area. The anticonvulsants and interlaminar epidural blocks were the most frequently used pharmacological and interventional methods for PHN treatment. For the interval of epidural block, intervals of 5 or more-weeks were the most popular. The proportion of PHN patients who get information from the mass media or the internet was only 0.8%.The incidence of suspected zoster sine herpete was only 0.1%. CONCLUSIONS: The treatment methods for PHN vary among hospitals. The establishment of treatment recommendation for PHN treatment is necessary. In addition, public relations activities are required in order to inform the patients of PHN treatments by pain clinicians.

Accidental intradural injection during attempted epidural block: A case report / 대한마취과학회지

Several cases of accidental subdural injection have been reported, but only few of them are known to be accidental intradural injection during epidural block. Therefore we would like to report our experience of accidental intradural injection. A 68-year-old female was referred to our pain clinic due to severe metastatic spinal pain. We performed a diagnostic epidural injection at T9/10 interspace under the C-arm guided X-ray view. Unlike the usual process of block, onset was delayed and sensory dermatomes were irregular range. We found out a dense collection of localized radio-opaque contrast media on the reviewed X-ray findings. These are characteristic of intradural injection and clearly different from the narrow wispy bands of contrast in the subdural space.

Participation of KATP Channels in the Antinociceptive Effect of Pregabalin in Rat Formalin Test

BACKGROUND: Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-Ca(2+)-channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with KATP channels in the rat formalin test. METHODS: IT PE-10 catheters were implanted in male Sprague-Dawley rats (250-300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) 20 microl (CON group); pregabalin 0.3, 1, 3 and 10 microg in NS 10 microl (PGB group); glibenclamide 100 microg in DMSO 5 microl with pregabalin 0.3, 1, 3 and 10 microg in NS 5 microl (GBC group). All the drugs were flushed with NS 10 microl. Immunohistochemistry for the KATP channel was done with a different set of rats divided into naive, NS and PGB groups. RESULTS: IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the KATP channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test. CONCLUSIONS: The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the KATP channel. However, pregabalin did not induce KATP channel expression in the spinal cord dorsal horn.

Estimation of Stellate Ganglion Block Injection Point Using the Cricoid Cartilage as Landmark Through X-ray Review

BACKGROUND: Stellate ganglion block is usually performed at the transverse process of C6, because the vertebral artery is located anterior to the transverse process of C7. The purpose of this study is to estimate the location of the transverse process of C6 using the cricoid cartilage in the performance of stellate ganglion block. METHODS: We reviewed cervical lateral neutral-flexion-extension views of 48 patients who visited our pain clinic between January and June of 2010. We drew a horizontal line at the surface of the cricoid cartilage in the neutral and extension views of cervical lateral x-rays. We then measured the change in the shortest distance from this horizontal line to the lowest point of the transverse process of C6 between the neutral and extension views. RESULTS: There was a statistically significant difference in the shortest distance from the horizontal line at the surface of the cricoid cartilage to the lowest point of transverse process of C6 between neutral position and neck extension position in both males and females, and between males and females in both neutral position and neck extension position. The cricoid cartilage level was 4.8 mm lower in males and 14.4 mm higher in females than the lowest point of transverse process of C6 in neck extension position. CONCLUSIONS: Practitioners should recognize that the cricoid cartilage has cephalad movement in neck extension. In this way, the cricoid cartilage can be still useful as a landmark for stellate ganglion block.

Opioid Therapy for Chronic Nonmaliganat Pain / 한양의대학술지

While acute pain is reasonably considered a symptom of disease or injury, chronic pain is a specific healthcare related problem as a disease in its own right. Even though the use of opioids in the management of chronic cancer pain has been growing, the chronic use of opioid medication for nonmalignant pain is still controversial. Most reports suggest that chronic opioid therapy can be effective for the reduction of chronic pain and for the improvement of function and health related quality of life. On the other hand, opioids are also associated with potentially serious harm including pharmacologic adverse effects and socio-economic problems such as abuse, addiction, and diversion. And there has been little evidence based background regarding long-term effectiveness. Although evidence is limited in the management of chronic nonmalignant pain, there are no adequate guidelines for the prescription of opioids in Korea. Hopefully, new guidelines should be developed as soon as possible to provide mechanism based and personalized medicine for carefully selected and monitored patients with chronic nonmalignant pain.

Comparison of the laryngeal view during intubation using Airtraq and Macintosh laryngoscopes in patients with cervical spine immobilization and mouth opening limitation / 대한마취과학회지

BACKGROUND: For patients suspicious of cervical spine injury, a Philadelphia cervical collar is usually applied. Application of Philadelphia cervical collar may cause difficult airway. The aim of this study was to evaluate the laryngeal view and the success rate at first intubation attempt of the Airtraq and conventional laryngoscopy in patients with simulated cervical spine injury after application of a Philadelphia cervical collar. METHODS: Anesthesia was induced with propofol, remifentanil, and rocuronium. After a Philadelphia cervical collar applied, patients were randomly assigned to tracheal intubation with an Airtraq (Group A, n = 25) or with conventional laryngoscopy (Group L, n = 25). Measurements included intubation time, success rate of first intubation attempt, number of intubation attempts, and percentage of glottic opening (POGO) score. Mean blood pressure and heart rate were also recorded at baseline, just before and after intubation. RESULTS: The success rate of the first attempt in Group A (96%) was significantly greater than with the Group L (40%). POGO score was significantly greater in Group A (84 +/- 20%) than in Group L (6 +/- 11%). The duration of successful intubation at first tracheal intubation attempt and hemodynamic changes were not significantly different between the two groups. CONCLUSIONS: The Airtraq offers a better laryngeal view and higher success rate at first intubation attempt in patients who are applied with a Philadelphia cervical collar due to suspicion of cervical spine injury.

The Use of Radiofrequency Lesion Generation on the Ganglion Impar for the Treatment of Chronic Coccygodynia: A case report / 대한마취과학회지

Coccygodynia is a common problem that is characterized by pain in the tailbone that radiates to the lower sacral and perineal areas. Coccygodynia may occur after a fall in the sitting position or damage to the sacrococcygeal ligament during a difficult vaginal delivery.Currently, the therapeutic options for coccygodynia are unclear, however, a number of treatment approaches have been proposed.In this case a favorable outcome was obtained by using a radiofrequency lesion generator to create a lesion on the ganglion impar in a patient with chronic coccygodynia.

Effects of Agmatine on GABAA Receptor Antagonist-induced Tactile Allodynia / 대한통증학회지

BACKGROUND: The intrathecal (IT) GABAA receptor antagonist, bicuculline (BIC), results in tactile allodynia (TA) through disinhibition in the spinal cord. Such disinhibition is considered to be an important mechanism for neuropathic pain. Agmatine, an endogenous polyamine, has a neuro-protective effect in the central nervous system. We investigated the analgesic effects and mechanisms of agmatine action on BIC-induced TA. METHODS: Male Sprague-Dawley rats, weighting 250-300 g, were subjected to implantations of PE-10 into the lumbar subarachnoid space for IT drug injection. Five days after surgery, either 10 microliter of normal saline (NS) or agmatine (30 microgram or 10 microgram) in 10 microliter NS were injected 10 min prior to BIC (10 microgram) or NMDA (5 microgram). We assessed the degree of TA (graded 0: no response, 1: mild response, 2: moderate response, 3: strong response) every 5 min for 30 min. Areas under curves and degree of TA were expressed as mean +/- SEM. Results were analyzed using one-way ANOVA followed by a Tukey test for multiple comparisons. P < 0.05 was considered significant. RESULTS: IT BIC-induced strong TA reached its peak and plateaued between 10 to 15 min. IT NS-NMDA induced mild transient TA for up to 15 min. Preemptive IT AG attenuated IT BIC-induced TA dose dependently and preemptive IT AG10 completely abolished the IT NMDA-induced TA. CONCLUSIONS: Preemptive IT AG attenuated the IT BIC-induced TA through inhibitory actions on postsynaptic NMDA receptor activation. AG might be a viable therapeutic option in the treatment of neuropathic pain.

The Expression of the Ca++ Channel alpha2delta Subunit and TRPM8 in the Dorsal Root Ganglion of Sympathetically Maintained Pain and Sympathetic Independent Pain Rat Models / 대한통증학회지

BACKGROUND: Peripheral nerve injury induces up-regulation of the calcium channel alpha2delta (alpha2delta) subunit and TRPM8 in the dorsal root ganglion (DRG) which might contribute to allodynia development. We investigated the expression of the alpha2delta subunit and TRPM8 in the DRG of sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) rat model. METHODS: For the SMP model, the L5 and L6 spinal nerves were ligated tightly distal to the DRG. For the SIP model, the tibial and sural nerves were transected, while the common peroneal nerve was spared. After a 7 day postoperative period, tactile and cold allodynia were assessed using von Frey filaments and acetone drops, respectively. Expression of the alpha2delta subunit and TRPM8 in the L5 and L6 DRG were subsequently examined by a Western blot. RESULTS: There were no significant differences between the two models for the thresholds of tactile and cold allodynia. Expression of the alpha2delta subunit in the ipsilateral DRG to the injury was increased as determined on a Western blot as compared to that in the contralateral or sham-operated DRG of the SMP model, but there was no difference in expression seen with the use of the SIP model. There was no difference in the expression of TRPM8 in the ipsilateral DRG to the injury and the contralateral or sham-operated DRG of either model. CONCLUSIONS: Up-regulation of the alpha2delta subunit in injured DRG may play a role that contributes to tactile allodynia development in SMP, but not TRPM8 to cold allodynia after peripheral nerve injury.

The Analgesic Effects of Intrathecal Pregabalin in Rat Formalin Tests: Comparison between Pre- and Post-treatment / 대한마취과학회지

BACKGROUND: Pregabalin is an analog of gamma aminobutyric acid, and selectively interacts with the alpha-2-delta subunit of the voltage dependent calcium channels. The aims of this study were to investigate the analgesic effects of intrathecal pregabalin in rat formalin tests and to compare between the pre-treatment and post-treatment group. METHODS: All experimental animals were randomly divided into pre- and post-treatment groups. In pre-treatment groups, pregabalin (0.003g, 0.01g, 0.03g, 0.1g, n = 6 at each group) was administered through the intrathecal catheter 10 min prior to formalin injection. In post-treatment groups, pregabalin (0.01g, 0.03g, 0.1g, 0.3g, n = 6 at each group) was administered through the catheter 10 min after formalin injection. Formalin (50 ml, 5%) was injected in the left hind paw. We counted the number of flinching as a pain behavior for 60 min to quantify the nociceptive response. RESULTS: The withdrawal responses which were represented by flinching count, were decreased dose dependently in the phase 2, in all groups (pre-treatment and post-treatment group), while there were less analgesic effects and ceiling effects in the phase 1. There was more significant decreasing flinching number in the pre-treatment group than that in the post-treatment group. CONCLUSIONS: Intrathecal pregabalin has preemptive analgesic effect and may be useful in the management of inflammation induced hyperalgesia.

Short Term Outcomes and Prognostic Factors Based on Radiofrequency Thermocoagulation on Lumbar Medial Branches / 대한통증학회지

BACKGROUND: Lumbar zygapophysial joints are a common source of chronic lower back pain and radiofrequency thermocoagulation (RF) of the medial branches (MB) has been shown to be effective at providing substantial pain relief for chronic low back pain.Therefore, we carried out this study to determine the short term outcomes and prognostic factors of RF on the MB of patients with lumbar facet syndrome. METHODS: We performed RF in fourteen patients who showed greater than 80% pain relief up to three times after a diagnostic MB block was conducted using 0.3 ml of 0.5% bupivacaine.Using 10 cm curved electrodes with 10-mm active tip, a 60 second, 80 degrees C lesion was made after electrical stimulation at 50 Hz for sensory and 2 Hz for motor nerve testing.The degree of pain relief was then assessed after 2 weeks, and again after 3 months using a visual analog scale (VAS) and a four point Likert scale.The outcome was regarded as 'success' if at least a 50% reduction in the VAS was observed.Possible prognostic factors between the two groups were also evaluated. RESULTS: The success rate was 71.4% (10/14) after three months of follow-up. However, there were transient complications, such as neuritis like syndrome, in 4 patients. In addition, short symptom duration and low minimal voltage (< 0.4 V) for sensory stimulation were shown to be the relevant prognostic factors for a successful outcome. CONCLUSIONS: RF may be an alternative to repeated MB block or intraarticular injection for palliation of lumbar facet syndrome. For better outcomes, early diagnosis and strict patient selection should be coupled with efforts to avoid anatomically incorrect RF.

Antiallodynic Effect of Pregabalin in Rat Models of Sympathetically Maintained and Sympathetic Independent Neuropathic Pain

Pregabalin binds to the voltage-dependent calcium channel alphadelta subunit and modulates the release of neurotransmitters, resulting in analgesic effects on neuropathic pain. Neuropathic pain has both sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) components. We studied the antiallodynic effects of pregabalin on tactile allodynia (TA) and cold allodynia (CA) in SMP-and SIP-dominant neuropathic pain models. Allodynia was induced by ligation of the L5 & L6 spinal nerves (SMP model) or by transection of the tibial and sural nerves (SIP model) in rats. For intrathecal drug administration, a PE-10 catheter was implanted through the atlantooccipital membrane to the lumbar enlargement. Pregabalin was administered either intraperitoneally (IP) or intrathecally (IT) and dosed up incrementally until an antiallodynic effect without sedation or motor impairment was apparent. TA was assessed using von Frey filaments, and CA was assessed using acetone drops. IP-administered pregabalin dose-dependently attenuated TA in both models and CA in the SMP model, but not CA in the SIP model. IT-administered pregabalin dose-dependently attenuated both TA and CA in both models. However, the dose response curve of IT-administered pregabalin in SMP was shifted to left from that of SIP and the ED50 of IT-administered pregabalin for CA in SMP was about 900 times less than that in SIP. These findings suggest that pregabalin exerts its antiallodynic effect mainly by acting at the spinal cord, and that IT-administered pregabalin has more potent antiallodynic effects in SMP. The alphadeltasubunit might be less involved in the CA in SIP.

The Interaction between Intrathecal NMDA Receptor Antagonist and 5-HT3 Receptor Agonist in the Rat Formalin Test / 대한마취과학회지

BACKGROUND: A single agent administered is not effective enough to block nociception. Combination of agents acting through different mechanisms may be one of the best ways for better analgesic methods. The purpose of this study was to investigate the spinally mediated analgesic interaction between 5-HT3 receptor agonist (m-CPBG) and NMDA receptor antagonist (MK801) in the rat formalin test. METHODS: A polyethylene catheter was inserted in the atlanto-occipital membrane to the thoracolumbar level of the spinal cord. On postoperative 7 day, the normal saline (n = 6), m-CPBG (10, 30, 100microgram: n = 18) and MK801 (0.1, 1, 10microgram: n = 18) were injected intrathecally before subcutaneous injection of 5% formalin. The combinations of each 1/2ED50 + 1/2ED50, 1/4ED50 + 1/4ED50, 1/8ED50 + 1/8ED50 were tested and the ED50 of the combination was determined. The experimental ED50 values were compared with the theoretical additive values. RESULTS: m-CPBG dose-dependently decreased the number of flinches in both phase 1 and 2. MK801 dose-dependently reduced the number of flinches in phase 2, but not in phase 1. The combination of m-CPBG and MK801 produced dose-dependent decreases of flinches on both phase 1 and 2. ED50 values (2.75microng for m-CPBG and 0.076microgram for MK801) of phase 2 in the combination were significantly less than the calculated additive values (20.0microgram for m-CPBG and 0.55microgram for MK801)(P<0.01). CONCLUSIONS: Intrathecally administered m-CPBG and MK801 had synergistic analgesic effects on formalin-induced hyperalgesia as well as antinociceptive effects in phase 1 on the rat formalin test.