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Background@#This study investigated the effect of an excess and a deficit of spinal 5-hydroxytryptamine (5-HT) on the mechanical allodynia and neuroglia activation in a rodent pain model of carrageenan inflammation. @*Methods@#Male Sprague–Dawley rats were implanted with an intrathecal (i.t.) catheter to administer the drug. To induce an excess or deficit of 5-HT in the spinal cord, animals were given either three i.t. 5-HT injections at 24-hour intervals or a single i.t. injection of 5,7-dihydroxytryptamine (5,7-DHT) before carrageenan inflammation.Mechanical allodynia was measured using the von Frey test for 0–4 hours (early phase) and 24–28 hours (late phase) after carrageenan injection. The changes in the activation of microglia and astrocyte were examined using immunofluorescence of the dorsal horn of the lumbar spinal cord. @*Results@#Both an excess and a deficit of spinal 5-HT had no or a minimal effect on the intensity of mechanical allodynia during the early phase but prevented the attenuation of mechanical allodynia during the late phase, which was observed in animals not treated with i.t. 5-HT or 5,7-DHT. Animals with an excess or deficit of 5-HT showed stronger activation of microglia, but not astrocyte, during the early and late phases, than did normal animals. @*Conclusions@#Imbalance in the descending 5-HT pathway in the spinal cord could aggravate the mechanical allodynia and enhance the activation of microglia, suggesting that the spinal 5-HT pathway plays an essential role in maintaining the nociceptive processing in balance between facilitation and inhibition in inflammatory pain caused by carrageenan inflammation.
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Background@#There is still unmet need in treating neuropathic pain and increasing awareness regarding the use of drug combinations to increase the effectiveness of treatment and reduce adverse effects in patients with neuropathic pain. @*Methods@#This study was performed to determine the individual and combined effects of pregabalin, tianeptine, and clopidogrel in a rat model of neuropathic pain.The model was created by ligation of the L5-L6 spinal nerve in male Sprague–Dawley rats; mechanical allodynia was confirmed using von Frey filaments. Drugs were administered to the intrathecal space and mechanical allodynia was assessed; drug interactions were estimated by isobolographic or fixed-dose analyses. @*Results@#Intrathecal pregabalin and tianeptine increased the mechanical withdrawal threshold in a dose-dependent manner, but intrathecal clopidogrel had little effect on the mechanical withdrawal threshold. An additive effect was noted between pregabalin and tianeptine, but not between pregabalin and clopidogrel. @*Conclusions@#These findings suggest that intrathecal coadministration of pregabalin and tianeptine effectively attenuated mechanical allodynia in the rat model of neuropathic pain. Thus, pregabalin plus tianeptine may be a valid option to enhance the efficacy of neuropathic pain treatment.
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Background@#Chemotherapy-induced peripheral neuropathy (CIPN) is a major reason for stopping or changing anticancer therapy. Among the proposed pathomechanisms underlying CIPN, proinflammatory processes have attracted increasing attention. Here we assessed the role of prostaglandin D2 (PGD2 ) signaling in cisplatininduced neuropathic pain. @*Methods@#CIPN was induced by intraperitoneal administration of cisplatin 2 mg/kg for 4 consecutive days using adult male Sprague-Dawley rats. PGD2 receptor DP1 and/or DP2 antagonists were administered intrathecally and the paw withdrawal thresholds were measured using von Frey filaments. Spinal expression of DP1, DP2, hematopoietic PGD synthase (H-PGDS), and lipocalin PGD synthase (L-PGDS) proteins were analyzed by western blotting. @*Results@#The DP1 and DP2 antagonist AMG 853 and the selective DP2 antagonist CAY10471, but not the DP1 antagonist MK0524, significantly increased the paw withdrawal threshold compared to vehicle controls (P = 0.004 and P < 0.001, respectively). Western blotting analyses revealed comparable protein expression levels in DP1 and DP2 in the spinal cord. In the CIPN group the protein expression level of L-PGDS, but not of H-PGDS, was significantly increased compared to the control group (P < 0.001). @*Conclusions@#The findings presented here indicate that enhanced PGD2 signaling, via upregulation of L-PGDS in the spinal cord, contributes to mechanical allodynia via DP2 receptors in a cisplatin-induced neuropathic pain model in rats, and that a blockade of DP2 receptor activation may present a novel therapeutic target for managing CIPN.
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Background@#Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. @*Methods@#Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague–Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. @*Results@#Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. @*Conclusions@#These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.
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Background@#Chemotherapy-induced peripheral neuropathy (CIPN) is a major reason for stopping or changing anticancer therapy. Among the proposed pathomechanisms underlying CIPN, proinflammatory processes have attracted increasing attention. Here we assessed the role of prostaglandin D2 (PGD2 ) signaling in cisplatininduced neuropathic pain. @*Methods@#CIPN was induced by intraperitoneal administration of cisplatin 2 mg/kg for 4 consecutive days using adult male Sprague-Dawley rats. PGD2 receptor DP1 and/or DP2 antagonists were administered intrathecally and the paw withdrawal thresholds were measured using von Frey filaments. Spinal expression of DP1, DP2, hematopoietic PGD synthase (H-PGDS), and lipocalin PGD synthase (L-PGDS) proteins were analyzed by western blotting. @*Results@#The DP1 and DP2 antagonist AMG 853 and the selective DP2 antagonist CAY10471, but not the DP1 antagonist MK0524, significantly increased the paw withdrawal threshold compared to vehicle controls (P = 0.004 and P < 0.001, respectively). Western blotting analyses revealed comparable protein expression levels in DP1 and DP2 in the spinal cord. In the CIPN group the protein expression level of L-PGDS, but not of H-PGDS, was significantly increased compared to the control group (P < 0.001). @*Conclusions@#The findings presented here indicate that enhanced PGD2 signaling, via upregulation of L-PGDS in the spinal cord, contributes to mechanical allodynia via DP2 receptors in a cisplatin-induced neuropathic pain model in rats, and that a blockade of DP2 receptor activation may present a novel therapeutic target for managing CIPN.
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Background@#Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. @*Methods@#Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague–Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. @*Results@#Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. @*Conclusions@#These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.
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BACKGROUND: Postoperative sore throat (POST) is a common adverse event after general anesthesia. The aim of this study was to evaluate the effectiveness of 2% lidocaine jelly applied on the single-lumen endotracheal tube (ETT) and thermal softening of the ETT, and a combination of both interventions on the development of POST. METHODS: Patients (n = 144) undergoing general anesthesia were randomly assigned to one of four groups: Control group (un-softened ETT lubricated with saline); Lidocaine group (un-softened ETT lubricated with 2% lidocaine jelly); Softened group (thermally softened ETT lubricated with saline); and Combined group (thermally softened ETT lubricated with 2% lidocaine jelly). Sore throat was evaluated at 0, 1, 6, 24, and 48 h after extubation. The occurrence of any postoperative complication was also assessed including hoarseness and coughing. RESULTS: No significant difference was observed in the severity of POST at all time points. However, the incidences of POST for overall (0–48 h) and the immediately following period (0 h) were significantly lower in the Combined group (52.9% and 47.1%) than in the Control group (79.4% and 76.5%), Lidocaine group (81.8% and 78.8%), and Softened group (82.9% and 74.3%). The overall incidence of hoarseness did not differ among the groups. No other postoperative complication was observed in any of the patients. CONCLUSIONS: No differences were observed in the severity of POST. However, 2% lidocaine jelly applied on thermally softened ETT reduced the overall incidence of POST. Therefore, this combined intervention could be considered as an alleviating strategy for POST.
Subject(s)
Humans , Anesthesia, General , Cough , Hoarseness , Incidence , Lidocaine , Pharyngitis , Postoperative ComplicationsABSTRACT
BACKGROUND: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. METHODS: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. RESULTS: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. CONCLUSIONS: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.
Subject(s)
Animals , Rats , Analgesia , Dopamine , Microdialysis , Nefopam , Pain Measurement , Spinal Cord , Spinal Cord Dorsal Horn , Sulpiride , Synaptic TransmissionABSTRACT
This article was inadvertently omitted Acknowledgments section for grant support.
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BACKGROUND: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processing is generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in the nerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in the carrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppresses the activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its role in the carrageenan model has not been reported. METHODS: Following intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Western blotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured. RESULTS: The expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals. The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the level of a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injection in the animals treated with 5,7-DHT than in the naive and control rats. CONCLUSIONS: The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhanced pain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.
Subject(s)
Animals , Humans , Male , Rats , 5,7-Dihydroxytryptamine , Blotting, Western , Carrageenan , Formaldehyde , Hyperalgesia , Inflammation , Phosphotransferases , Rats, Sprague-Dawley , Spinal CordABSTRACT
BACKGROUND: Nefopam has shown an analgesic effect on acute pain including postoperative pain. The reuptake of monoamines including serotonin and noradrenaline has been proposed as the mechanism of the analgesic action of nefopam, but it remains unclear. Although alpha-adrenergic agents are being widely used in the perioperative period, the role of noradrenergic modulation in the analgesic effect of nefopam has not been fully addressed. METHODS: Changes in the antinociceptive effect of intrathecal (i.t.) nefopam against formalin-elicited flinching responses were explored in Sprague-Dawley rats pretreated with i.t. 6-hydroxydopamine (6-OHDA), which depletes spinal noradrenaline. In addition, antagonism to the effect of nefopam by prazosin and yohimbine was evaluated to further elucidate the antinociceptive mechanism of i.t. nefopam. RESULTS: Pretreatment with i.t. 6-OHDA alone did not alter the flinching responses in either phase of the formalin test, while it attenuated the antinociceptive effect of i.t. nefopam significantly during phase 1, but not phase 2. The antagonist of the alpha-2 receptor, but not the alpha-1 receptor, reduced partially, but significantly, the antinociceptive effect of i.t. nefopam during phase 1, but not during phase 2. CONCLUSIONS: This study demonstrates that spinal noradrenergic modulation plays an important role in the antinociceptive effect of i.t. nefopam against formalin-elicited acute initial pain, but not facilitated pain, and this action involves the spinal alpha-2 but not the alpha-1 receptor.
Subject(s)
Acute Pain , Formaldehyde , Nefopam , Norepinephrine , Oxidopamine , Pain Measurement , Pain, Postoperative , Perioperative Period , Prazosin , Rats, Sprague-Dawley , Serotonin , Spinal Cord , YohimbineABSTRACT
BACKGROUND: To manage intractable cancer pain, an alternative to systemic analgesics is neuraxial analgesia. In long-term treatment, intrathecal administration could provide a more satisfactory pain relief with lower doses of analgesics and fewer side-effects than that of epidural administration. However, implantable drug delivery systems using intrathecal pumps in Korea are very expensive. Considering cost-effectiveness, we performed epidural analgesia as an alternative to intrathecal analgesia. METHODS: We retrospectively investigated the efficacy, side effects, and complications of epidural morphine and local anesthetic administration through epidural catheters connected to a subcutaneous injection port in 29 Korean terminal cancer patients. Patient demographic data, the duration of epidural administration, preoperative numerical pain rating scales (NRS), side effects and complications related to the epidural catheterization and the drugs, and the numerical pain rating scales on the 1st, 3rd, 7th and 30th postoperative days were determined from the medical records. RESULTS: The average score for the numerical pain rating scales for the 29 patients decreased from 7 +/- 1.0 at baseline to 3.6 +/- 1.4 on postoperative day 1 (P < 0.001). A similar decrease in pain intensity was maintained for 30 days (P < 0.001). Nausea and vomiting were the most frequently reported side effects of the epidural analgesia and two patients (6.9%) experienced paresthesia. CONCLUSIONS: Epidural morphine and local anesthetic infusion with a subcutaneous pump seems to have an acceptable risk-benefit ratio and allows a high degree of autonomy to patients with cancer pain.
Subject(s)
Humans , Analgesia , Analgesia, Epidural , Analgesics , Catheterization , Catheters , Drug Delivery Systems , Injections, Subcutaneous , Korea , Medical Records , Morphine , Nausea , Pain Management , Paresthesia , Retrospective Studies , Vomiting , Weights and MeasuresABSTRACT
BACKGROUND: The frequent and distressing adverse events (AEs) of postoperative nausea and vomiting (PONV) are of major concern in 63-84% of adult patients undergoing thyroidectomy. We conducted this prospective study to compare two prophylactic strategies; sevoflurane combined with ramosetron and propofol-based total intravenous anesthesia in a homogenous group of non-smoking women undergoing total thyroidectomy. METHODS: In the current prospective study, we enrolled a consecutive series of 64 female patients aged between 20 and 65 years with an American Society of Anesthesiologists physical status of I or II who were scheduled to undergo elective total thyroidectomy under general anesthesia. Patients were randomized to either the SR (sevoflurane and remifentanil) group or the TIVA group. We evaluated the incidence and severity of PONV, the use of rescue anti-emetics and the severity of pain during the first 24 h after surgery. RESULTS: There were no significant differences in the proportion of the patients with a complete response and the Rhodes index, including the occurrence score, distress score and experience score, between the two groups. In addition, there were no significant differences in the proportion of the patients who were in need of rescue anti-emetics or analgesics and the VAS scores between the two groups. CONCLUSIONS: In conclusion, TIVA and ramosetron prophylaxis reduced the expected incidence of PONV in women undergoing total thyroidectomy. In addition, there was no significant difference in the efficacy during the first 24 h postoperatively between the two prophylactic regimens.
Subject(s)
Adult , Female , Humans , Analgesics , Anesthesia, General , Anesthesia, Intravenous , Antiemetics , Incidence , Postoperative Nausea and Vomiting , Propofol , Prospective Studies , ThyroidectomyABSTRACT
BACKGROUND: Tianeptine is an antidepressant drug which is used for treating depression. Interestingly, the tianeptine has shown antinociceptive effects within a variety of nociceptions. The aim of this study is to investigate the antiallodynic effects of tianeptine in neuropathic pain rats and also determine the involvements of serotonergic, alpha-2 adrenergic and adenosine receptors at the spinal level. METHODS: Neuropathic pain was induced by ligation of left lumbar at 5th and 6th spinal nerves in male Sprague-Dawley rats. PE-10 catheters were placed into the thoracolumbar subarachnoid space for drug injections. Mechanical allodynia was evaluated by measuring the withdrawal threshold to von Frey filament when applying on the plantar surface of rats. The effects of intrathecal tianeptine were observed at 15, 30, 60, 90, 120, 150, 180 minutes after delivery. Antagonists for serotonergic (dihydroergocristine), alpha-2 adrenergic (yohimbine) and adenosine (CGS 15943) receptors were intrathecally administered 10 minutes prior to tianeptine in order to evaluate the involvement of both receptors. RESULTS: Intrathecal tianeptine increased dose-dependently at the withdrawal threshold in the ligated paw. Pretreatment with intrathecal dihydroergocristine, yohimbine and CGS 15943 antagonized the antiallodynic effects of tianeptine. CONCLUSIONS: These results suggested that intrathecal tianeptine attenuates the spinal nerve ligation induced tactile allodynia. Serotonergic, alpha-2 adrenergic and adenosine receptors are all involved in the antiallodynic effects of tianeptine at the spinal level.
Subject(s)
Animals , Humans , Male , Rats , Adenosine , Catheters , Depression , Dihydroergocristine , Hyperalgesia , Ligation , Neuralgia , Nociception , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha-2 , Receptors, Purinergic P1 , Spinal Nerves , Subarachnoid Space , YohimbineABSTRACT
BACKGROUND: The aims of this study were to compare the efficacy of sevoflurane inhalation alone, intravenous remifentanil alone, and the combination of sevoflurane inhalation and remifentanil as pretreatment for the prevention of rocuronium-induced withdrawal movement in pediatric patients. METHODS: In this prospective, randomized study, 90 American Society of Anesthesiologists physical status I or II pediatric patients aged 3 to 10 years were randomly allocated to one of three treatment groups: The Group S comprising the patients receiving sevoflurane inhalation, the Group R comprising those doing intravenous remifentanil 0.5 microg/kg and the Group C comprising those doing sevoflurane inhalation+intravenous remifentanil 0.5 microg/kg. The response of the patients was graded based on a 4-point scale. RESULTS: The overall incidence of withdrawal movement on rocuronium injection was 54% (16/30) in the Group S, 57% (17/30) in the Group R and 17% (5/30) in the Group C. There was no significant difference in the incidence of withdrawal movements on rocuronium injection between the Group S and Group R. In addition, the incidence of withdrawal movements and generalized movement on rocuronium injection was significantly lower in the Group C as compared with the Group S and R (P < 0.05). CONCLUSIONS: Our results indicate not only that there was no significant difference in the degree of the effect in lowering the incidence of withdrawal movements on rocuronium injection between sevoflurane inhalation and intravenous remifentanil but also that it was significantly higher when combined with intravenous remifentanil as compared with the single use of sevoflurane inhalation or intravenous remifentanil.
Subject(s)
Child , Humans , Incidence , Inhalation , Pediatrics , Prospective StudiesABSTRACT
BACKGROUND: Nefopam, a non-opiate analgesic, has been regarded as a substance that reduces the requirement for morphine, but conflicting results have also been reported. The inhibition of monoamine reuptake is a mechanism of action for the analgesia of nefopam. The spinal cord is an important site for the action of monoamines however, the antinociceptive effect of intrathecal nefopam was not clear. This study was performed to examine the antinociceptive effect of intrathecal (i.t.) nefopam and the pattern of pharmacologic interaction with i.t. morphine in the formalin test. METHODS: Male Sprague-Dawley rats were implanted with an i.t. catheter, and were randomly treated with a vehicle, nefopam, or morphine. Formalin was injected into the hind-paw 10 min. after an i.t. injection of the above experiment drugs. After obtaining antinociceptive ED50 of nefopam and morphine, the mixture of nefopam and morphine was tested for the antinociceptive effect in the formalin test at a dose of 1/8, 1/4, 1/2 of ED50, or ED50 of each drug followed by an isobolographic analysis. RESULTS: Intrathecal nefopam significantly reduced the flinching responses in both phases of the formalin test in a dose-dependent manner. Its effect, however, peaked at a dose of 30 microg in phase 1 (39.8% of control) and 10 microg during phase 2 (37.6% of control). The isobolograhic analysis indicated an additive interaction of nefopam and morphine during phase 2, and a synergy effect in antinociception during phase 1. CONCLUSIONS: This study demonstrated that i.t. nefopam produces an antinociceptive effect in formalin induced pain behavior during both phases of the formalin test, while interacting differently with i.t. morphine, synergistically during phase 1, and additively during phase 2.
Subject(s)
Animals , Humans , Male , Rats , Analgesia , Catheters , Formaldehyde , Morphine , Nefopam , Pain Measurement , Rats, Sprague-Dawley , Spinal CordABSTRACT
BACKGROUND: Thalidomide has been recognized as having an anti-allodynic effect against neuropathic pain induced by spinal nerve ligation. Its clinical beneficial effects are mainly derived from its immune-modulating property, which is known to influence the analgesic action of morphine. The possible characteristics of systemic interactions between thalidomide and morphine in the context of spinal nerve ligation-induced neuropathic pain were examined in rats. METHODS: Neuropathic pain was induced by ligation of the L5/6 spinal nerves in male Sprague-Dawley rats and mechanical allodynia was assessed using von Frey filaments. The ED50 was calculated for thalidomide and for morphine, and the mixture of both drugs was intraperitoneally administered at different doses of ED50 of each drug (1/8, 1/4, 1/2, 1/1 of ED50) to obtain the experimental ED50 value for the combination of thalidomide and morphine. Isobolographic analysis was used to evaluate the characteristics of drug interactions between morphine and thalidomide. RESULTS: The ED50 of thalidomide was three-fold higher than that of morphine. The experimental ED50 value of the mixture of thalidomide and morphine was significantly lower than the calculated theoretical ED50 value. Isobolographic analysis revealed a synergistic interaction for anti-allodynic effect after intraperitoneal delivery of the thalidomide-morphine mixture. CONCLUSIONS: These results suggest that thalidomide acts synergistically with morphine to produce an anti-allodynic effect in neuropathic pain induced by spinal nerve ligation in rats. Thus, the combination of thalidomide with morphine may be one of the useful strategies in the management of neuropathic pain.
Subject(s)
Animals , Male , Rats , Analgesics , Drug Interactions , Drug Synergism , Hyperalgesia , Injections, Intraperitoneal , Ligation , Morphine , Neuralgia , Rats, Sprague-Dawley , Spinal Nerves , ThalidomideABSTRACT
Refractory angina pectoris is defined as angina refractory to optimal medical treatment and standard coronary revascularization procedures. Despite recent therapeutic advances, patients with refractory angina pectoris are not adequately treated. Spinal cord stimulation is a minimally invasive and reversible technique which utilizes electrical neuromodulation by means of an electrode implanted in the epidural space. It has been reported to be an effective and safe treatment for refractory angina pectoris. We report a case of spinal cord stimulation which has effectively relieved chest pain due to coronary artery disease in a 40-year-old man. This is the first report of spinal cord stimulation for treatment of refractory angina pectoris in South Korea.
Subject(s)
Adult , Humans , Angina Pectoris , Chest Pain , Coronary Artery Disease , Electrodes , Epidural Space , Republic of Korea , Spinal Cord , Spinal Cord StimulationABSTRACT
BACKGROUND: The injection pain of microemulsion propofol is frequent and difficult to prevent. This study examined the prevention of pain during microemulsion propofol injection by pretreatment with different doses of remifentanil or saline, and premixing of lidocaine. METHODS: One hundred sixty ASA physical status 1-2 adult patients scheduled for elective surgery were enrolled into one of four groups (n = 40, in each). The patients received saline (group LS), remifentanil 0.3 microg/kg (group LR 0.3), remifentanil 0.5 microg/kg (group LR 0.5), or remifentanil 1.0 microg/kg (group LR 1.0), and after 90 seconds received an injection of 2 mg/kg microemulsion propofol premixed with lidocaine 40 mg. Pain was assessed on a four-point scale during microemulsion propofol injection. RESULTS: The incidence of microemulsion propofol-induced pain was significantly lower in the LR 0.3, LR 0.5 and LR 1.0 groups than in the LS group (37.5%, 12.5% and 10% vs 65%, respectively). The LR 0.5 and LR 1.0 groups showed significantly less frequent and intense pain than the LR 0.3 group. However, both incidence and severity of pain were not different between LR 0.5 and LR 1.0 groups. CONCLUSIONS: The combination of remifentanil and lidocaine is effective in alleviating pain associated with a microemulsion propofol injection compared with just lidocaine. Remifentanil 0.5 microg/kg had a similar analgesic effect compared to the 1.0 microg/kg dose.
Subject(s)
Adult , Humans , Incidence , Lidocaine , Piperidines , PropofolABSTRACT
BACKGROUND: There is growing interest in the anesthetic approach using total intravenous anesthesia (TIVA) with propofol and remifentanil for the prevention of postoperative nausea and vomiting (PONV). The aim of this study was to compare between the two anesthetic techniques for preventing PONV in the patients undergoing mastoidectomy with tympanoplasty. METHODS: After obtaining informed consent, 62 patients aged between 20 to 60 years undergoing elective mastoidectomy and tympanoplasty were randomized into two equal study groups: group P/R (n = 31) included patients undergoing TIVA with propofol and remifentanil, and group S/R (n = 31) included patients undergoing balanced anesthesia with sevoflurane and remifentanil. The incidences of PONV and complete response (no PONV, no rescue) were assessed at 1 and 24 h after surgery, using the Rhodes Index. Also, the usage of rescue antiemetics and pain intensity were recorded. RESULTS: The Rhodes Index including the occurrence score, distress score and experience score was significantly lower in the P/R group compared to that in the S/R group during the study period (P < 0.05), and the incidence of complete response was significantly higher in the P/R group compared to that in the S/R group, during the first 24 h after surgery. 4 patients in the S/R group requested antiemetics during the first 1 h after surgery. There were no significant differences in pain intensity among groups. CONCLUSIONS: Compared to balanced anesthesia with sevoflurane and remifentanil, TIVA with propofol and remifentanil was followed by significantly lower incidence and severity of PONV.