Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study.

BACKGROUND: Genetic factors such as single-nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study was to identify SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. METHODS: Associations between 659,636 SNPs and the incidence of PONV 24 h after surgery in a limited sample of 24 female patients were assessed using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. RESULTS: The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). CONCLUSIONS: We identified a novel SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. TRIAL REGISTRATION: This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903 , date of registration: June 27, 2016, retrospectively registered.

Changes in synaptic transmission of substantia gelatinosa neurons after spinal cord hemisection revealed by analysis using in vivo patch-clamp recording.

BACKGROUND: After spinal cord injury, central neuropathic pain develops in the majority of spinal cord injury patients. Spinal hemisection in rats, which has been developed as an animal model of spinal cord injury in humans, results in hyperexcitation of spinal dorsal horn neurons soon after the hemisection and thereafter. The hyperexcitation is likely caused by permanent elimination of the descending pain systems. We examined the change in synaptic transmission of substantia gelatinosa neurons following acute spinal hemisection by using an in vivo whole-cell patch-clamp technique. RESULTS: An increased spontaneous action potential firings of substantia gelatinosa neurons was detected in hemisected rats compared with that in control animals. The frequencies and amplitudes of spontaneous excitatory postsynaptic currents and of evoked excitatory postsynaptic currentss in response to non-noxious and noxious stimuli were not different between hemisected and control animals. On the contrary, the amplitude and frequency of spontaneous inhibitory postsynaptic currents of substantia gelatinosa neurons in hemisected animals were significantly smaller and lower, respectively, than those in control animals (P < 0.01). Large amplitude and high-frequency spontaneous inhibitory postsynaptic currents, which could not be elicited by mechanical stimuli, were seen in 44% of substantia gelatinosa neurons in control animals but only in 17% of substantia gelatinosa neurons in hemisected animals. In control animals, such large amplitude spontaneous inhibitory postsynaptic currents were suppressed by spinal application of tetrodotoxin (1 µM). Cervical application of lidocaine (2%, 10 µl) also inhibited such large amplitude of inhibitory postsynaptic currents. The proportion of multi-receptive substantia gelatinosa neurons, which exhibit action potential firing in response to non-noxious and noxious stimuli, was much larger in hemisected animals than in control animals. CONCLUSIONS: These suggest that substantia gelatinosa neurons receive tonic inhibition by spinal inhibitory interneurons which generate persistent action potentials. Spinal hemisection results in hyperexcitation of substantia gelatinosa neurons at least in part by eliminating the tonic descending control of spinal inhibitory interneurons from supraspinal levels.

Association of µ-opioid receptor gene (OPRM1) haplotypes with postoperative nausea and vomiting.

Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the µ-opioid receptor gene (OPRM1) might be associated with individual differences in opioid sensitivity, as well as with the incidence and severity of postoperative nausea and vomiting (PONV). The goal of the present study was to determine, in a cohort of Japanese surgical patients, genotypes and haplotypes of several SNPs in the OPRM1 gene, and their association with PONV during the early (first 24 h) postoperative period. We examined the incidence and severity of PONV, during the first 24 h after surgery, in 85 Japanese patients receiving intravenous patient-controlled analgesia fentanyl analgesia for postoperative pain control. Eight tag SNPs of the OPRM1 gene (rs1799971, A/G; rs510769, G/A; rs4870266, G/A; rs3798683, G/A; rs1323042, A/C; rs609623, C/T; rs9397685, A/G; and rs644261, C/G) were selected based on their minor allele frequency (>10%) and linkage disequilibrium strength (<80%), and genotyped for haplotype analysis and determination of associations with PONV. Only one out of eight investigated SNPs, rs9397685, in the intronic part of the OPRM1 gene was associated with differences in the occurrence and severity of PONV. We also found four common haplotypes with a frequency of >10% in the investigated patients, including GGGAACAC (33%), AGGGACAC (19%), GGGAACGC (12%), and AGAGACAC (10%). The severity of PONV in carriers of the GGGAACGC haplotype was significantly lower than in the carriers of the other haplotypes (P < 0.05). One intronic SNP, rs9397685, and haplotypes constructed from eight SNPs within the OPRM1 gene locus might be involved in the severity of PONV associated with general anesthesia and opioid administration. This novel finding, if validated and verified in larger and additional ethnic cohorts, might contribute to better knowledge of the contribution of the OPRM1 gene to PONV.

A prospective randomized multicenter comparative study of BLM-240 (desflurane) versus sevoflurane in Japanese patients.

The present study was conducted to evaluate the efficacy and safety of BLM-240 (desflurane) in comparison to sevoflurane in Japanese patients. A total of 216 patients were enrolled in this randomized comparative study at 15 medical institutions. The patients received either BLM-240 with 50-70 % N2O in O2 (n = 111), BLM-240 with 30 % O2 in air (n = 55), or sevoflurane with 50-70 % N2O in O2 (n = 50). Efficacy was evaluated by an efficacy rate based on an efficacy evaluation criteria and recovery time to extubation from the discontinuation of the anesthetics. Safety was evaluated by incidence of adverse drug reactions (ADR) and other clinical indicators. The efficacy rate of BLM-240 was 98.8 % (164/166 patients), indicating that BLM-240 is effective as an anesthetic. Time from discontinuation of anesthetic delivery to extubation was 9.7 ± 0.6 min in the BLM-240/N2O group and 14.3 ± 0.9 min in the sevoflurane/N2O group, meeting the pre-defined non-inferiority criteria of BLM-240 to sevoflurane. There was no statistically significant difference in the incidence of total ADR between the BLM-240 group (62.0 %) and sevoflurane group (48.0 %). The results indicate that BLM-240 is an effective and safe inhalation anesthetic in Japanese patients.

Genetic differences in response properties of rostral ventromedial medulla neurons to the µ-opioid receptor agonist DAMGO in mouse inbred strains.

BACKGROUND: Opioid sensitivity varies among individuals. Although opioids can act partly in the rostral ventromedial medulla (RVM), which has a major role in pain perception, individual differences in the functions of the RVM in response to opioids have not been elucidated. Pain-related behavior among inbred mouse strains may reflect individual differences in sensitivity to pain. We therefore investigated the changes in action potentials of RVM neurons in response to opioid in different mouse strains. METHODS: Two inbred strains of mice (A/J and CBA/J) were used. Their behavior to noxious stimuli was measured after intracerebroventricular injection of the µ-opioid receptor agonist, DAMGO. Using an in vivo extracellular recording technique, action potentials from single RVM neurons and their functional type (ON-like, OFF-like, or NEUTRAL-like cell) were identified. Evoked responses of the RVM neurons to noxious stimuli were recorded before and after DAMGO administration. RESULTS: The behavioral study showed that the dose-dependent antinociceptive effect in the A/J strain was significantly stronger than in the CBA/J strain. The electrophysiological study showed that the number of inhibitory OFF-like cells in A/J mice was significantly larger than in CBA/J mice (P<0.01), and that the evoked responses of neurons of A/J mice were inhibited significantly more than in CBA/J mice both for ON-like and OFF-like cells (P<0.01). CONCLUSIONS: The strain differences in the physiological properties of RVM neurons corresponded to the behavioral strain differences. Genetic differences may contribute to the interindividual variation seen in opioid-induced analgesia.

Landiolol, an ultra-short-acting ß1-blocker, more effectively terminates atrial fibrillation than diltiazem after open heart surgery: prospective, multicenter, randomized, open-label study (JL-KNIGHT study).

BACKGROUND: Recent studies have suggested that esmolol is the first choice for rate control in patients with postoperative atrial fibrillation (AF) after coronary artery bypass surgery, but side-effects of esmolol such as hypotension are problematic. To overcome this problem, landiolol, an ultra-short-acting ß(1)-blocker with a less negative inotropic effect than esmolol, has been developed. The aim of the present study was to investigate whether landiolol was effective for both rate control and conversion to normal sinus rhythm (NSR). METHODS AND RESULTS: A prospective, randomized, open-label comparison between i.v. landiolol and diltiazem in patients with postoperative AF was undertaken between January 2008 and June 2009 in Japan. Of 335 patients included in the analysis, 71 patients went into AF. Among these 71 patients, conversion to NSR within 8h after onset of AF occurred in 19 of 35 patients (54.3%) in the landiolol group vs. 11 of 36 patients (30.6%) in the diltiazem group (P<0.05). The incidence of hypotension was lower in the landiolol group (4/35, 11.4%) compared with the diltiazem group (11/36, 30.6%; P<0.05). The incidence of bradycardia was also lower in the landiolol group (0%) compared with the diltiazem group (4/36, 11.1%; P<0.05). CONCLUSIONS: Landiolol is more effective and safer than diltiazem for patients with postoperative AF after open heart surgery.

[A case of coronary stent thrombosis occurring repeatedly in the perioperative period].

A 60-year-old man with angina was scheduled for total gastrectomy, splenectomy, and cholecystectomy. Bare-metal stents were implanted into his left anterior descending coronary artery four weeks before the operation. Aspirin and clopidogrel were administered until one week before the operation and then injection of to 15,000 units of heparin per day was given. Anesthesia was maintained with sevoflurane, remifentanil and fentanyl. At 330 minutes after starting the operation, 2-mm ST segment elevation was observed and it recovered immediately. After the operation, new 9-mm ST segment elevation in leads V2-V6 was observed. Emergent cardiac catheterization showed occlusion of the coronary artery with in-stent thrombosis. An additional stent was implanted and 10,000 units of heparin per day was injected. After five days, new stent thrombosis occurred and an additional stent was implanted. Administration of aspirin, clopidogrel and cilostazol was started immediately. Anesthesiologists should pay attention to the kind of coronary stent, consider the timing of the operation, and continue administration of aspirin.

[A phase II clinical study of once-a-day fentanyl citrate patch in patients with cancer pain--switching from once-every-three-days fentanyl patch to once-a-day fentanyl citrate patch].

We examined the efficacy and safety of a new transdermal fentanyl citrate patch (HFT-290), which was applied once daily in patients with cancer pain who were receiving a stable dose of once-every-three-day application transdermal fentanyl patch [TDF (72 hr)]. After TDF (72 hr) was applied for three days at the same dose used before starting the study, treatment was switched to HFT-290 (once daily) for 9 days. The analgesic effect was judged with a 5-point scale based on each patient's assessment of pain on a 100-mm visual analog scale (VAS). Seventy-eight patients were enrolled. The efficacy rate (95% confidence interval) of the analgesic effect at the time of final removal of HFT-290 (the primary efficacy end-point) was high at 83.9% (71.7-92.4%; 47/56 patients). Furthermore, based on the shift of the VAS, good pain control was achieved after switching. All adverse drug reactions were either mild or moderate, and the main reactions were those commonly observed with opioid analgesics. No respiratory depression was observed. HFT-290 demonstrated good tolerability after switching from TDF (72 hr) and provided stable pain control.

[Technical advantages of ultrasound-guided obturator nerve block compared with the nerve stimulating technique].

BACKGROUND: We investigated the onset time of obturator nerve block and time required for the nerve block comparing two groups in a prospective randomized study. METHODS: Obturator nerve block was performed in 37 cases by either nerve stimulation guide (NS group) or nerve stimulation and ultrasound guide (US group) with 10 ml of 1.5% lidocaine adding 1:200000 epinephrine. RESULTS: There was no significant difference between the onset time in the NS group (6.1 min) and that in the US group (5.7 min). The time required for the nerve block (4.2 min vs 1.7 min) was significantly shorter, and the frequency of needle advancement for the optimal position (4.7 vs 1.7) was significantly smaller in the US group than in the NS group (P<0.05). CONCLUSIONS: Ultrasound imaging facilitated the identification of obturator nerves between adductor muscles. Ultrasound-guided obturator nerve block is a safe, quick and useful technique.

A new reusable skin-protective sphygmomanometer cuff.

OBJECTIVE: Repeated blood pressure measurement with a sphygmomanometer often produces skin redness and subcutaneous bleeding in clinical settings. Recently, we have produced a new reusable skin-protective cuff with an additional sheet. METHODS: We evaluated skin damage and blood pressure measurement accuracy when using the new cuffs. We also evaluated upper arm deformity by CT scan during cuff inflation. Pulse wave amplitude evaluation was carried out with an NIBP simulator and our original system. RESULTS: The use of this cuff reduced subcutaneous bleeding and pain with cuff inflation and enabled accurate blood pressure measurement. CONCLUSION: We produced a new skin protective reusable sphygmomanometer cuff.

[Landiolol hydrochloride is useful for anesthetic management of cesarean section in a patient with Basedow disease].

We report successful anesthetic management of elective cesarean section in a 30-year-old patient with Basedow disease using landiolol hydrochloride, a short-acting beta-1 adrenergic blocker of which greatest advantages are its short duration of action, rapid clearance and high beta-1 selectivity. The patient received landiolol for the prevention of aggravated tachycardia and tachyarrhythmia during cesarean section. She received landiolol continuous infusion at a rate of 5 microg x kg x min(-1) to 8 microg x kg x min(-1) until the uneventful delivery of the infant with good Apgar score, under combined spinal epidural anesthesia (CESA). We could maintain maternal hemodynamics stable leading to good post-cesarean uterus contraction. No severe adverse effects were observed in the infant. In conculusion, landiolol is useful for maintaining the hemodynamics stable in a pregnant woman with Basedow disease and keeping the infant safe from any adverse effect by infusion of landiolol.

Pulmonary embolism caused by a carbon dioxide blower during off-pump coronary artery bypass grafting.

We report a rare case of pulmonary embolism (PE) caused by a carbon dioxide (CO2) blower during off-pump coronary artery bypass grafting (OPCAB). When the anastomosis of the right internal thoracic artery to left anterior descending artery was performed, the operator tore the right ventricle outflow track (RVOT) that was adjacent to the left anterior descending artery. Immediately after the anastomosis and repair of the torn RVOT with CO2 blower, the systolic pulmonary artery pressure (PAP) increased from 28 to 64 mmHg, and end-tidal CO2 decreased from 32 to 12 mmHg. Because transesophageal echocardiograph (TEE) showed numerous gas bubbles in the main pulmonary artery, we diagnosed PE caused by invasion of CO2 gas bubbles via the torn RVOT. Although a CO2 blower is useful to enhance visualization of the anastomosis during OPCAB, it should not be used for the venous system because it may cause CO2 embolism.

[Usefulness of preoperative epidural catheterization under radiographic monitoring in anesthesia for endovascular abdominal aneurysm repair].

In Japan, endovascular abdominal aneurysm repair became one of the standard procedures in 2006. It has been performed in 8 patients at our hospital. We try epidural anesthesia with sedation for treatment because of the good control of blood pressure and immobilization of the patient. We usually perform epidural catheterization one day before the operation to avoid epidural hematoma due to heparinization during the operation. We usually use radiographic monitoring for safe and precise insertion of the catheter into the epidural space. Epidural catheterization with radiographic monitoring is useful for safe and reliable epidural analgesia.

[Elderly patient with non specific multiple ulcer of the small intestine associated with nutritional edema and anemia].

An 83-year-old woman had felt malaise. Blood examination showed renal failure, anemia, and hypoproteinemia. On the 7th day, she suddenly had tarry stool. But, gastroscopy and colonfiberscopy disclosed no remarkable abnormality on the mucosal surface of the stomach, the duodenum and the large intestine. On the 10th day, her symptom became aggravated, and emergency laparotomy and endoscopy in the small intestine was scheduled. After the jejunotomy, she underwent endoscopy of the small intestine. The endoscopic examination showed multiple ulcer of the jejunum, and she underwent jejunectomy. Pathologic examination diagnosed her as having non specific multiple ulcer of the small intestine with jejunal lesion.

Effects of sepsis on the neuromuscular blocking actions of d-tubocurarine on rat adductor and abductor laryngeal muscles.

PURPOSE: We evaluated the effects of sepsis on the neuromuscular blocking actions of d-tubocurarine (dTc) in the lateral cricoarytenoid (LCA) and posterior cricoarytenoid (PCA) muscles, an adductor muscle and an abductor muscle of the vocal cords, respectively, in vitro. METHODS: Sepsis was induced in rats by cecal ligation and puncture (CLP) to elicit panperitonitis. Electromyograms (EMGs) and endplate potentials (EPPs) were recorded from the LCA and PCA muscles of CLP-operated septic rats and sham-operated nonseptic rats, using extracellular and intracellular microelectrodes, respectively. RESULTS: EMG and EPP (amplitude and quantum content) were depressed by dTc, but the dTc-induced neuromuscular blocking effects were attenuated by sepsis. The suppressive effects of dTc on EMG and EPP (amplitude and quantum content) were less intense in the LCA muscle than in the PCA muscle under both sepsis and nonsepsis conditions. CONCLUSION: Our study shows that sepsis has a depressive effect on dTc-induced neuromuscular blocking actions at both the adductor and abductor muscles of vocal cords in the larynx.

Ultrasound-aided unilateral epidural block for single lower-extremity pain.

We report an ultrasound-aided unilateral epidural block, employed in two patients, to provide better analgesia and motor function for lower-extremity pain. The patient in case 1 was a 72-year-old woman who suffered pain arising from Herpes zoster rash on the left leg (the second lumbar nerve area). A left-dominant continuous unilateral epidural block was performed to reduce her pain. After confirming the L2/3 epidural space and needle direction using ultrasound imaging, epidural cannulation was performed. Continuous infusion of 4 ml h(-1) of 1% lidocaine through the epidural catheter eliminated the herpetic pain in the left leg, maintaining motor function and normal sensation in her right leg. The patient in case 2 was a 35-year-old man whose complaint was postoperative pain in his left knee during passive movement. Dependent-side (left-side) dominant ultrasound-aided continuous unilateral epidural block, the same procedure as that used in case 1, was performed at the L3/4 intervertebral space. His left knee pain was clearly reduced, with partial paralysis, but motor function in his right leg was completely normal during the continuous epidural block with 4 ml h(-1) of 0.2% ropivacaine. Ultrasound imaging around the epidural space facilitated effective unilateral epidural block for single lower-extremity pain in both patients. This technique could decrease possible side effects and improve patient satisfaction during continuous nerve block by maintaining motor function and sensation in the nondependent side.

[Anesthetic management using veno-veno bypass for emergent tracheostomy in a patient with acute epiglottitis].

We report anesthetic management using veno-veno bypass (V-V bypass) for emergent tracheostomy in a patient with acute epiglottitis. A 72-year-old woman complained of dyspnea due to acute epiglottitis, and emergent tracheostomy was planned for her. Since physical and optical fiberscopic examinations indicated a high risk of airway collapse during anesthetic induction, we planned to do tracheostomy under V-V bypass in order to maintain oxygenation. V-V bypass was established using the right femoral and jugular veins in an awake condition. After starting V-V bypass, tracheostomy was performed under intravenous propofol anesthesia. During surgery, bispectral index was maintained below 60. Surgery was carried out with ease and uneventfully. The patient had no complications due to V-V bypass postoperatively.

Successful extracorporeal membranous oxygenation for a patient with life-threatening transfusion-related acute lung injury.

A case of transfusion-related acute lung injury (TRALI) that was successfully treated with extracorporeal membranous oxygenation (ECMO) is reported. A 58-year-old male patient underwent hepatectomy, and pulmonary edema occurred after the administration of fresh-frozen plasma and packed red cells. In the postoperative period, the impaired oxygenation progressively worsened, resulting in life-threatening hypoxemia, despite vigorous treatments. ECMO was therefore applied to the patient as a method of safe emergency support. Aggressive treatments under ECMO led to the successful improvement of the impaired oxygenation. TRALI is recognized as part of acute respiratory distress syndrome (ARDS). As a treatment for ARDS, ECMO does not cure the underlying disease of the lungs, however, with ECMO, TRALI, usually improves within 96 h with respiratory support. ECMO for TRALI-induced lethal hypoxemia is useful for providing time to allow the injured lung to recover. It is suggested that ECMO might be a useful option for the treatment of TRALI-induced, potentially lethal hypoxemia.

Neutralization of receptor for advanced glycation end-products and high mobility group box-1 attenuates septic diaphragm dysfunction in rats with peritonitis.

OBJECTIVES: : To determine the relationship between intra-abdominal sepsis-induced high mobility group-box 1 and diaphragm contractile performance and to determine the inhibitory effects of antibodies for high mobility group-box 1 and receptor for advanced glycation end-products on septic peritonitis-induced diaphragmatic dysfunction, lipid peroxidation, and intracellular signal transduction in the rat diaphragm. In animal models of sepsis, production of reactive oxygen species has been shown to elicit diaphragmatic dysfunction. Extracellularly released high mobility group-box 1 can bind to cell surface receptors, such as receptor for advanced glycation end-products, eliciting inflammatory responses that lead to the development of sepsis. DESIGN: : Prospective laboratory study. SETTING: : University laboratory. SUBJECTS: : Wistar rats (n = 186). INTERVENTIONS: : Intra-abdominal sepsis was induced, using cecal ligation and perforation. In experiment 1, serum and diaphragm homogenates were obtained from sham-operated rats and from cecal ligation and perforation rats at 4-hr intervals postoperatively. In experiment 2, anti-high mobility group-box 1 and anti-receptor for advanced glycation end-products antibodies were administered 4 hrs and 8 hrs after cecal ligation and perforation to determine their effects on cecal ligation and perforation-induced diaphragm dysfunction, reactive oxygen species-related variables, and intracellular signal transduction. MEASUREMENTS AND MAIN RESULTS: : In experiment 1, cecal ligation and perforation induced serum and diaphragmatic high mobility group-box 1 within 8 hrs postoperatively with a decline in diaphragmatic force generation at 12 hrs after cecal ligation and perforation. In experiment 2, anti-receptor for advanced glycation end-products and anti-high mobility group-box 1 antibodies significantly attenuated cecal ligation and perforation-induced diaphragmatic dysfunction in a dose-related manner. Diaphragmatic malondialdehyde concentration and phosphorylation level of extracellular signal-regulated kinase 1/2 in the groups treated with these antibodies were significantly lower than those in the nontreated group. Anti-receptor for advanced glycation end-products antibody downregulated high mobility group-box 1 expression in the diaphragm during sepsis. CONCLUSIONS: : Cecal ligation and perforation induces high mobility group-box 1 in the diaphragm and increases serum high mobility group-box 1 level as a late-phase mediator, decreasing contractile performance by high mobility group-box 1 receptor for advanced glycation end-products interaction-mediated reactive oxygen species production. These findings suggested an important role of receptor for advanced glycation end-products-high mobility group-box 1 interaction in diaphragmatic dysfunction induced by lipid peroxidation in rats with intra-abdominal sepsis.

Reduction of bone cancer pain by activation of spinal cannabinoid receptor 1 and its expression in the superficial dorsal horn of the spinal cord in a murine model of bone cancer pain.

BACKGROUND: Bone cancer pain has a strong impact on the quality of life of patients, but it is difficult to treat. Therefore, development of a novel strategy for the treatment of bone cancer pain is needed for improvement of patient quality of life. This study examined whether selective spinal cannabinoid receptor 1 (CB1) activation alleviates bone cancer pain and also examined the spinal expression of CB1. METHODS: A bone cancer pain model was made by implantation of sarcoma cells into the intramedullary space of the mouse femur. In behavioral experiments, the authors examined the effects of activation of spinal CB1 and inhibition of metabolism of endocannabinoid on bone cancer-related pain behaviors. Immunohistochemical experiments examined the distribution and localization of CB1 in the superficial dorsal horn of the spinal cord using specific antibodies. RESULTS: Spinal CB1 activation by exogenous administration of a CB1 agonist arachidonyl-2-chloroethylamide reduced bone cancer-related pain behaviors, including behaviors related to spontaneous pain and movement-evoked pain. In immunohistochemical experiments, although mu-opioid receptor 1 expression was reduced in the superficial dorsal horn ipsilateral to the site of implantation of sarcoma cells, CB1 expression was preserved. In addition, CB1 was mainly expressed in the axon terminals, but not in the dendritic process in the superficial dorsal horn. CONCLUSION: Spinal CB1 activation reduced bone cancer-related pain behavior. Presynaptic inhibition may contribute to the analgesic effects of spinal CB1 activation. These findings may lead to novel strategies for the treatment of bone cancer pain.