Predictive factors of postoperative acute pain in laparoscopic inguinal hernia repair in men: A single-centre retrospective study in Japan.

INTRODUCTION: Laparoscopic inguinal hernia repair has significantly reduced the incidence of postoperative acute and chronic pain compared to open repair, but it remains problematic. This study's purpose was to retrospectively identify predictive factors of acute pain after laparoscopic inguinal hernia repair. METHODS: We reviewed the medical records of 193 patients. After excluding atypical cases and female patients, 156 patients were analysed. Factors affecting rescue analgesic requirements were investigated via multivariable logistic regression analysis. Independent variables included age, body mass index, analgesics used during surgery and surgical factors (unilateral/bilateral, primary/recurrent). The degree of postoperative pain and the hospital stay duration after surgery were also investigated. RESULTS: Of the 156 patients, 40 (25.6%) required rescue analgesics. Patients under 60 years of age were about seven times more likely to need rescue analgesics than patients over 80 years of age. Primary surgery patients were about 5.5 times more likely to need rescue analgesics than recurrent surgery patients. The maximum verbal rating scale score was less than 3 in 89% of patients. All patients were discharged by two days postoperatively. CONCLUSION: Laparoscopic inguinal hernia repair results in less postoperative acute pain. However, analgesia management should be considered prudently for younger patients and primary surgery patients.

Aspiration pneumonia and anesthesia techniques in hip fracture surgery in elderly patients: A retrospective cohort study using administrative data.

Purpose: Aspiration pneumonia is a critical issue. General anesthesia may suppress the airway's protective reflex. However, aspiration pneumonia is also observed in patients who undergo hip fracture surgery under spinal anesthesia. The aim of this study was to investigate the relationship between anesthesia methods and aspiration pneumonia as well as the predictive factors of aspiration pneumonia in elderly patients undergoing hip fracture surgery. Methods: The medical records of 19,809 patients aged ≥60 years who underwent hip fracture surgery under general or spinal anesthesia were reviewed. After propensity score matching, the anesthesia methods affecting the occurrences of aspiration pneumonia and other complications were investigated via logistic regression and instrumental variable analyses. Predictive factors of aspiration pneumonia were also investigated in all subjects using a multivariable logistic regression analysis. Results: Among the 11,673 general anesthesia patients and 8136 spinal anesthesia patients, aspiration pneumonia occurred in 356 patients (1.8%). Post-propensity score matching the incidences of aspiration pneumonia with general and spinal anesthesia were 1.8% and 1.5%, respectively (p = 0.158); other pulmonary complications were 1.5% and 1.5%, respectively (p = 0.893); and the mortality rates were 1.4% and 1.2%, respectively (p = 0.219). The predictive factors of aspiration pneumonia were advanced age, male sex, lean body, cerebrovascular disease, dementia, and dependency for activities of daily living (eating). Conclusion: Spinal and general anesthesia showed similar incidences of aspiration pneumonia in elderly hip fracture surgery. Regardless of the anesthesia method, great care should be taken, especially in elderly patients with the identified predictive factors.

Olanzapine attenuates postoperative cognitive dysfunction in adult rats.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is associated with poor quality of life and difficulty working. Its impact may be greater in middle-aged patients than in elderly patients. Neuroinflammation is reported to be a main cause of POCD. Olanzapine has been reported to improve learning and memory functions. We therefore investigated olanzapine's effectiveness and mechanisms in an adult rat POCD model. METHODS: Six-month-old rats underwent laparotomy and lipopolysaccharide (LPS group) or LPS + olanzapine (OLA group) intraperitoneal injection or anesthesia alone (CON group) 1 week after a Barnes maze training session. A Barnes maze test trial was then conducted the day after surgery or anesthesia. The microglial activity in the hippocampus and cytokine levels were measured by Iba1 staining and enzyme-linked immunosorbent assay, respectively. RESULTS: The OLA group had significantly higher success rates of Barnes maze trial than the LPS group. The success rate in time of the OLA group was inferior to that of the CON group. On the other hand, the success rate in distance of the OLA group was similar to that of the CON group. Iba1 staining areas in the LPS and OLA groups were larger than that in the CON group; however, the staining area in the OLA group was smaller than that of the LPS group. Plasma interleukin-1ß concentration in the LPS and OLA groups was significantly higher than that in the CON group; however, there was no significant difference between the LPS and OLA groups. CONCLUSION: Olanzapine attenuated both spatial cognitive dysfunction and microglial activity of the hippocampus, which were induced by surgery and LPS injection. These effects were unrelated to inflammatory cytokine concentrations in plasma and hippocampus.

Comparison of peripheral nerve block with local infiltration analgesia regarding walking ability after total knee replacement: A retrospective, propensity-score matched-pair cohort study.

PURPOSE: It is unclear whether perioperative analgesic techniques affect the functional outcome of total knee replacement (TKR). We investigated the effects of peripheral nerve block (PNB) and local infiltration (LI) on walking ability after TKR. METHODS: The medical records of 7143 patients who underwent TKR using general anesthesia with PNB or LI techniques were reviewed. Factors affecting independence and/or improvement of walking after surgery were investigated using multivariate regression analysis. To adjust for baseline differences and minimize selection bias for the chosen analgesic technique, patients were matched by propensity scores. RESULTS: The multivariate regression analysis showed that PNB was associated with independence and/or improvement of walking. Of the 7143 patients, 2755 (39%) received PNB analgesia and 4388 (61%) LI analgesia. After the propensity score matching, the analgesic types were not associated with walking ability. Independence reflected by the total score of daily living activities was higher in the PNB group than in the LI group. The PNB group started rehabilitation later but performed rehabilitation for longer in the initial period than the LI group. Consumption levels of fentanyl, pentazocine, and antiemetics were lower in the PNB group than in the LI group. The PNB group had fewer hypertensive episodes during surgery than the LI group. There was no significant difference in total hospitalization costs between the two groups. CONCLUSIONS: No significant difference in postoperative walking ability was found between PNB and LI groups. However, PNB offered some advantages over LI. Future detailed investigations to improve TKR surgery are needed.

Factors associated with physiological postoperative pyrexia.

AIM: Postoperative pyrexia is generally a physiological response to surgery. It is a common problem and burden for both patients and surgeons. This study aimed to investigate the incidence and duration of physiological postoperative pyrexia and to retrospectively identify the prognostic factors associated with it. METHODS: We reviewed the medical records of 462 patients who underwent surgery for adenomyosis under general anesthesia. Postoperative pyrexia was defined as an axillary temperature of at least 38°C occurring for at least 4 h after the surgery up to the next morning. Long-duration pyrexia was defined as a fever recovery period of >3 days. RESULTS: Of the 367 patients included in this study, 234 (64%) developed postoperative pyrexia and 260 (71%) needed >3 days to recover the normal temperature (<37°C). Multivariate analyses revealed that the administration of an amino acid-enriched solution and non-administration of flurbiprofen were associated with postoperative pyrexia. Scale of surgery (bleeding volume + weight of removed adenomyosis and other tissue), body mass index, and decreased body temperature during surgery were not associated with postoperative pyrexia. Long-duration pyrexia was associated with the scale of surgery but not with the administration of an amino acid-enriched solution and flurbiprofen. CONCLUSION: More than half of the patients developed postoperative pyrexia. Postoperative pyrexia was related to the administration of an amino acid-enriched solution and flurbiprofen. Long-duration pyrexia was associated with the scale of surgery.

Postoperative daily living activities of geriatric patients administered general or spinal anesthesia for hip fracture surgery: A retrospective cohort study.

PURPOSE: Maintaining independence after hip fracture repair is important for geriatric patients and general welfare. We investigated the effects of anesthetic methods on postoperative activities of daily living (ADLs) following hip fracture surgery in elderly patients. METHODS: The medical records of 12,342 patients aged ≥65 years who underwent typical surgeries for hip fracture using either general anesthesia or spinal anesthesia were reviewed. To adjust for baseline differences and minimize selection bias for the chosen method of anesthesia, patients were matched by propensity scores. Factors affecting the deterioration in ADLs during hospital stay were also investigated in all subjects using a multivariate logistic regression analysis. Eating, grooming, toileting, bathing, and walking were selected as the ADL parameters, as they are considered important for an independent life. RESULTS: Of the 12,342 patients, 6918 (56.1%) received general anesthesia and 5424 (43.9%) received spinal anesthesia. After the propensity score matching, the anesthesia types were not associated with ADL scores except toileting at discharge. Results from the multivariate logistic regression analysis showed that the types of anesthesia were not associated with deterioration in ADL scores. Advanced age, male sex, high Charlson Comorbidity Index scores, psychiatric disease, no administration of nonsteroidal anti-inflammatory drugs, and short length of hospital stay were associated with deterioration in ADL scores. CONCLUSION: The anesthesia types were not associated with ADL dependency except toileting at discharge. Spinal anesthesia adversely affected toilet use at hospital discharge. However, anesthesia types were not factors that affected deterioration in ADL during hospital stay in elderly patients who underwent hip fracture surgery.

Allopregnanolone suppresses mechanical allodynia and internalization of neurokinin-1 receptors at the spinal dorsal horn in a rat postoperative pain model.

BACKGROUND: To identify a new strategy for postoperative pain management, we investigated the analgesic effects of allopregnanolone (Allo) in an incisional pain model, and also assessed its effects on the activities of the primary afferent fibers at the dorsal horn. METHODS: In experiment 1, 45 rats were assigned to Control, Allo small-dose (0.16 mg/kg), and Allo large-dose (1.6 mg/kg) groups (n = 15 in each). The weight bearing and mechanical withdrawal thresholds of the hind limb were measured before and at 2, 24, 48, and 168 h after Brennan's surgery. In experiment 2, 16 rats were assigned to Control and Allo (0.16 mg/kg) groups (n = 8 in each). The degree of spontaneous pain was measured using the grimace scale after the surgery. Activities of the primary afferent fibers in the spinal cord (L6) were evaluated using immunohistochemical staining. RESULTS: In experiment 1, the withdrawal threshold of the Allo small-dose group was significantly higher than that of the Control group at 2 h after surgery. Intergroup differences in weight bearing were not significant. In experiment 2, intergroup differences in the grimace scale scores were not significant. Substance P release in the Allo (0.16 mg/kg) group was significantly lower than that in the Control group. CONCLUSIONS: Systemic administration of Allo inhibited mechanical allodynia and activities of the primary afferent fibers at the dorsal horn in a rat postoperative pain model. Allo was proposed as a candidate for postoperative pain management.

Olanzapine Attenuates Mechanical Allodynia in a Rat Model of Partial Sciatic Nerve Ligation.

BACKGROUND: Neuropathic pain is a global clinical problem; nevertheless, nerve injury treatment methods remain limited. Olanzapine has antinociceptive and anti-nueropathic properties; however, its preventive effects have not been assessed in nerve injury models. METHODS: We prepared a partial sciatic nerve ligation (Seltzer model) or sham-operated model in male Sprague-Dawley rats under isoflurane anesthesia. In a pre-treatment study, we administered olanzapine (10 mg/kg) intraperitoneally 1 h before nerve ligation. In post-treatment and dose-dependent studies, we injected 3 different doses of olanzapine intraperitoneally 1 h after nerve ligation. Mechanical allodynia was measured before and 7 days after surgery. Immunohistochemical analysis using anti-Iba-1 antibody was used to assess the effect of olanzapine at the spinal level. RESULTS: In the pre-treatment study, median withdrawal thresholds of the normal saline groups were significantly lower than those of the sham-operated groups; however, those of the olanzapine (10 mg/kg) and sham-operated groups were not different. In the post-treatment and dose-dependent studies, the median withdrawal thresholds of the olanzapine (2.5 mg/kg) and normal saline groups were not different; however, those of the olanzapine (10 and 50 mg/kg) groups were significantly higher than those of the normal saline groups. Olanzapine did not have a significant effect on the density of Iba-1 staining. CONCLUSIONS: Olanzapine attenuated mechanical allodynia dose-dependently in the Seltzer model. This anti-allodynic effect of olanzapine was observed even when injected 1 h after nerve ligation. This effect of olanzapine appeared to be unrelated to microglia activation in the ipsilateral dorsal horn of the lumbar spinal cord.

[Retrograde Ascending Aortic Dissection during Thoracic Endovascular Stent Graft Repair: A Case Report].

A 66-year-old man (166 cm and 64 kg) with a history of hypertension was diagnosed with a.chronic aortic dissection (DeBakey IIIa type). He underwent thoracic endovascular aortic repair (TEVAR) under general anesthesia (sevoflurane and remifentanil) in an angiography room. After deploying a stent graft (Zenith TX2, Cook Japan, Tokyo) in the descending aorta via the right femoral artery, we checked the condition of the stent by angiography. No remarkable change of vital signs was observed. However, the angiography revealed a decrease in blood flow of both brachiocephalic and left common carotid arteries. The decision was made to operate immediately. The patient was transferred to the operating room under sedation with propofol. Cardiopulmonary bypass commenced 1 hour and 25 minutes after the decision to operate. Exploration of the aortic arch confirmed a retrograde ascending aortic dissection (rAAD). Ascending-arch vascular prosthesis was performed during circulatory arrest. The patient was extubated successfully the day after surgery. The present case demonstrates an intraoperative rAAD following stent placement TEVAR is believed to be less invasive compared to surgical treatment. However, it should be noted that TEVAR could provoke life-threatening complications such as rAAD.

[Group A streptococcus-induced toxic shock syndrome in pregnancy: a case report of cesarean section].

Group A streptococcus (GAS)-induced toxic shock syndrome (TSS) in pregnancy is rare, but its clinical course is fulminant. The mortality rates of mother and fetus are reported to be 58 and 66%, respectively. We report a case of GAS-TSS after cesarean section. A 38-year-old pregnant woman of 38 weeks gestation was admitted to our hospital because of vomiting, fever of 39 degrees C, and continuous abdominal pain with scanty genital bleeding. She had complained of sore throat several days before. One hour after admission, external fetal monitoring revealed periodic pulse deceleration to 90 x beats min(-1). The emergent cesarean section was performed under general anesthesia. Approximately 8 hours after the cesarean section, she developed coma, shock and respiratory insufficiency requiring intubation. Streptococcus pyogens were isolated from her blood sample and the patient met criteria for GAS-TSS. She was treated with antibiotics (penicillin and clindamycin), antithrombin III, recomodulin, catecholamins, and continuous hemodialysis with filtration of toxins. Although the patient recovered and was discharged on 63rd day, the infant died on postpartum day 4. Early recognition and intensive treatment for GAS is recommended in a late stage pregnancy with an episode of sore throat, vomiting, high fever, strong labor pain, and DIC signs.

[Glidescope performance in tracheal intubation by novice laryngoscopists: a manikin study].

BACKGROUND: The Glidescope is a novel video laryngoscope designed for difficult airway management. It is expected to be a useful device for inexperienced users but published data have been limited. Using a manikin, we compared the performance of the Glidescope with those of the Airway scope and Macintosh laryngoscope in tracheal intubation by inexperienced and experienced operators. METHODS: Seventeen nurses and 17 anesthesiologists were included for the present study. The intubation time, success rate, the pressure exerted on the upper teeth during intubation, visibility of the vocal cord, the most favorable device, and operability of each device (VAS) were recorded. RESULTS: In the inexperienced group, there was no significant difference in the intubation time among the three devices. Visibility and operability of Glidescope and Airwayscope were better than those of Macintosh laryngoscope in the inexperienced group. The pressure on the upper teeth by Glidescope was higher than that by Macintosh laryngoscope, though most inexperienced operators did not feel apprehensive about teeth injury. CONCLUSIONS: The Glidescope was a useful device for the inexperienced operators. However, instructors should notice that inexperienced laryngoscopists tend to push the upper teeth by the Glidescope.

Intracranial hemorrhage from undiagnosed metastatic brain tumor during general anesthesia.

A patient with endometrial cancer presented with intracranial hemorrhage from an undiagnosed metastatic brain tumor during abdominal radical hysterectomy. Since she was neurologically intact, a systematic examination for brain metastasis had not been performed preoperatively. After the surgery, she had delayed recovery from general anesthesia with right hemiplegia and aphasia. Computed tomography and magnetic resonance imaging showed left putaminal hemorrhage from brain metastasis.

Tracheomalacia after reoperation for an adenomatous goiter located in a unique position.

Tracheomalacia after thyroidectomy is a life-threatening situation. However, it is difficult to predict postoperative tracheal obstruction with certainty. A case of a 74-year-old woman with a long-standing adenomatous goiter (98 g) is reported. She had undergone partial right lobe thyroidectomy 54 years earlier. After total thyroidectomy, she was reintubated and required a tracheostomy because of tracheomalacia. The right residual thyroid tumor weighed only 5 g, but it extended to the retrotracheal space. Because the right lobe had stretched the membranous wall of the trachea over a long period of time, the tracheal lumen was thought to have collapsed because of loss of the foundation of the tracheal cartilage (the residual right lobe) along with the supportive surrounding tissue (the left lobe) after surgery. The present case suggests that the occurrence of tracheomalacia could be attributed to reoperation and retrotracheal extension. Thus far, six preoperative predictive factors for the development of severe postoperative respiratory obstruction have been reported: goiter for more than 5 years, preoperative recurrent laryngeal nerve palsy, significant tracheal narrowing and/or deviation, retrosternal extension, difficult endotracheal intubation, and thyroid cancer. Two more factors, reoperation and retrotracheal extension of tumor, may also be risks for airway obstruction after thyroidectomy.

Forces applied to the maxillary incisors during tracheal intubation and dental injury risks of intubation by beginners: a manikin study.

OBJECTIVES: We wished to determine whether dental injuries during intubation would occur more frequently when performed by inexperienced beginners. We measured the laryngoscopic force exerted on maxillary teeth of a modified manikin by experienced anesthesiologists and unexperienced medical students and estimated the injury risk. METHODS: Thirty-two anesthesiologists and 32 medical students participated in this study. Each testee performed tracheal intubation in two scenarios in a random order. In Scenario 1, the testee performed tracheal intubation for a manikin as a patient with normal dentition, in an emergency type situation. In Scenario 2, the testee performed tracheal intubation for a manikin as a patient with unstable dentition, in a routine anesthetic situation. RESULTS: The mean peak forces in Scenarios 1 and 2 were 6.1 and 1.1 N in the experienced testee group and 7.7 and 3.8 N in the unexperienced testee group, respectively (Scenario 2, p < 0.05). The unexperienced group applied higher forces than the experienced group in the nonemergency situation. However, the maximum force applied by the inexperienced group was 40.2 N, which is substantially lower than the maximum bite force of normal incisors (150-200 N). CONCLUSION: Our results suggest that the experience levels of the laryngoscopists are not a major determinant of dental injuries in patients with healthy dentition.

A novel association of alveolar capillary dysplasia, atypical duodenal atresia, and subglottic stenosis.

Alveolar capillary dysplasia (ACD), which is a rare and lethal congenital pulmonary anomaly found in newborns, begins its onset or causes deterioration of the infant's condition some time after birth. Various congenital anomalies in combination with ACD have been reported, except for subglottic stenosis. Therefore, we aim to report a novel association in a case of ACD with the combination of atypical duodenal atresia and subglottic stenosis. The male infant was scheduled for duodeno-duodenostomy because a double-bubble sign was observed on a chest radiograph. He arrived at the operating theater without any symptoms. After induction of general anesthesia, although mask ventilation was performed without difficulties throughout the entire procedure, oxygen saturation values of the upper and lower extremities dissociated after several attempts of intubation. Surgery was canceled because of instability of the respiratory condition. Respiratory insufficiency worsened progressively, and the infant died at 5 days of age. An autopsy confirmed ACD and revealed cartilaginous subglottic stenosis, which had made intubation difficult. This report highlights the hazards of the onset and worsening of ACD, and the importance of thorough echocardiography before surgery when atypical duodenal atresia is suspected. Anesthesiologists should also be prepared for the difficulty of intubation.

Licking decreases phosphorylation of extracellular signal-regulated kinase in the dorsal horn of the spinal cord after a formalin test.

BACKGROUND: Nociceptive behaviors might attenuate pain sensation. Phosphorylation of extracellular signal-regulated kinase (pERK) was recently reported to be induced by noxious stimuli in dorsal horn neurons. We investigated, in a formalin test, whether pERK of the dorsal horn is affected by licking. METHODS: Twenty-four adult male rats were divided into four groups: control, formalin test, restricted control, and restricted formalin test. Ten percent formalin was injected subcutaneously into the left rear paw of the formalin test and restricted formalin test groups. The control and formalin test group rats were kept in a clear plastic chamber, whereas the restricted control and restricted formalin test group rats were kept in a modified-restraint, pipe-shaped chamber. All rats were killed after 25 min. Twelve sections of the lumbar spinal cord were processed for p-ERK immunohistochemistry using the avidin-biotin peroxidase method. RESULTS: The number of p-ERK positive cells in the restricted formalin test group was significantly higher than in the other three groups in the ipsilateral-side superficial dorsal horn (P < 0.05). However, there was no significant difference between the formalin test group and the two control groups in pERK expression. CONCLUSION: Licking decreased pERK of the spinal cord of the formalin test group. The findings suggested that licking attenuated the pain of the formalin test.

Unilateral adrenalectomy attenuates hemorrhagic shock-induced analgesia in rats.

PURPOSE: To assess the importance of the pituitary adrenal axis in producing stress-induced analgesia (SIA) after hemorrhagic shock, we performed formalin tests after hemorrhage and reinfusion in unilaterally adrenalectomized or sham-operated rats. METHODS: Fifty-two adult Sprague-Dawley rats were divided into seven groups: sham-operation normotensive (n = 8), sham-operation shock (n = 8), adrenalectomy normotensive (n = 7), adrenalectomy shock (n = 7), sham-operation shock + yohimbine (n = 7), sham-operation normotensive + corticosterone (n = 7), and adrenalectomy shock + corticosterone (n = 8). The left adrenal gland was cauterized 24 h before the experiment. The mean blood pressure in the shock groups was kept at 50-60 mmHg for 30 min by draining arterial blood. After the blood-reinfusion or observation period, 10% formalin was injected into the rear paw. Nociceptive behaviors and locomotion were observed and rated for 1 h, using the criteria of Dubuisson and Dennis. In 12 other sham-operated and adrenalectomized rats, plasma adrenalin, noradrenalin, and corticosterone concentrations were measured before and after hemorrhagic shock. RESULTS: Although the sham-operation shock group showed a lower pain score, the adrenalectomy shock group showed nociceptive behavior similar to that in the normotensive groups. Yohimbine did not affect the SIA; however, corticosterone administration reversed the effects of the adrenalectomy on the SIA. The plasma corticosterone levels in the unilaterally adrenalectomized rats were lower than those in the sham-operated rats and did not increase after hemorrhagic shock. CONCLUSION: These results suggest that adrenocortical systems play an important role in hemorrhagic shock-induced SIA.

Site of fresh gas inlet and ratios of the delivered fraction and inspired fraction of inhaled isoflurane and sevoflurane in low-flow anesthesia.

PURPOSE: The use of low-flow anesthesia causes a discrepancy between the delivered fraction (FD) and the inspired fraction (FI) of inhaled gases. We compared the FI/FD ratios of a new circle (fresh gas inlet located between the inspiratory valve and the patient) to those of the conventional circle (fresh gas inlet located between the inspiratory valve and the CO2 absorber) in low-flow isoflurane and sevoflurane anesthesia, using three anesthetic machines (Dräger NM-GS, Dräger Fabius-GS, and ACOMA KMA-1300-III). METHODS: Eighty-two patients were randomly assigned to three experimental groups. For experiment 1, 32 patients were allocated to the NM-GS conventional/new, NM-GS new/conventional, ACOMA conventional/new, and ACOMA new/conventional groups. For experiment 2, 14 patients were allocated to ACOMA conventional/conventional and ACOMA new/new groups to measure isoflurane FI/FD ratios. For experiment 3, 36 patients were allocated to ACOMA conventional/conventional, ACOMA new/new, Fabius conventional/conventional, and Fabius new/new to measure sevoflurane FI/FD ratios. RESULTS: In experiment 1, the NM-GS showed no significant changes in the FI/FD ratios. However, in the ACOMA, the new circle improved the FI/FD ratio. In experiment 2, the isoflurane FI/FD ratios in the new circle of the ACOMA were significantly higher than those in the conventional circle. In experiment 3, the sevoflurane FI/FD ratios in the new circle of both the ACOMA and the Fabius were significantly higher than those in the conventional circles. CONCLUSION: The positioning of the fresh gas inlet between the inspiratory valve and the patient improved the FI/FD ratios of both isoflurane and sevoflurane during low-flow anesthesia in two decoupling-style anesthetic machines (ACOMA and Fabius).

Systemic clonidine activates neurons of the dorsal horn, but not the locus ceruleus (A6) or the A7 area, after a formalin test: the importance of the dorsal horn in the antinociceptive effects of clonidine.

PURPOSE: In order to clarify the principal site for the antinociceptive effects of clonidine, we investigated the nociceptive behavior and neural activity (c-fos staining) of the dorsal horn (DH), locus ceruleus (LC), and A7 area after a formalin test in normal saline- or clonidine-injected rats. METHODS: Thirty-six rats were divided into 6 groups as follows: formalin test + saline (FS); formalin test + clonidine (1 mg.kg(-1)) (FC1); formalin test + clonidine (10 mg.kg(-1)) (FC10); saline (S); clonidine (1 mg.kg(-1)) (C1); and clonidine (10 mg.kg(-1)) (C10). Normal saline or clonidine was injected intraperitoneally 30 min before the formalin test. In the FS, FC1, and FC10 groups, 10% formalin was injected into the left rear paw. All rats were killed 2.5 h after normal saline or clonidine injection. Sections of the lumbar spinal cord, LC, and A7 area were processed for c-fos immunohistochemistry using the avidin-biotin peroxidase complex method. To evaluate the sedative effects of clonidine, we investigated the loss of righting reflex (LORR) for 90 min in 6 other rats as follows: clonidine (1 mg.kg(-1)) (n = 3) and clonidine (10 mg.kg(-1)) (n = 3). RESULTS: The FC10 group showed fewer nociceptive behaviors and higher c-fos expression in the DH, but not in the A7 area, as well as lower c-fos expression in the LC than rats in the FS and FC1 groups (P < 0.05). The C10 group showed lower c-fos expression in the LC than that of rats in the S and C1 groups (P < 0.05). No rats exhibited LORR. CONCLUSION: The antinociceptive effects of clonidine might be mediated primarily by neural activity in the DH.

Moderate hypercapnia-induced anesthetic effects and endogenous opioids.

The purpose of this report is to explore the mechanisms of hypercapnia-induced antinociception. We carried out three experiments, the first to confirm whether moderate hypercapnia induces anesthetic effects, the second to determine whether naloxone reverses the anesthetic effects, and the third to evaluate whether beta-endorphin is related to the anesthetic effects. In a pre-test, we determined the optimal CO(2) concentration in a chamber which would cause moderate hypercapnia in rats. Eighteen rats were divided into control, hypercapnia, and hypercapnia plus naloxone groups in experiment 1. The naloxone group rats were injected with naloxone (10 mg/kg) intraperitoneally before gas inhalation. After 60 min gas inhalation, 10% formalin was injected into the left rear paw of all rats, and nociceptive behaviors were observed for 1 h. In experiment 2, 11 rats were divided into control and hypercapnia groups. The brain was removed and fixed under pentobarbital anesthesia. Sections were immunostained for c-Fos and beta-endorphin (ACTH) with the ABC method. All neurons double-labeled for c-Fos and beta-endorphin (ACTH) in the arcuate nucleus were counted by blinded investigators. Moderate hypercapnia (PaCO(2) 83+/-7 mmHg) reduced nociceptive behavior in the formalin test and naloxone pre-treatment attenuated this phenomenon. However, beta-endorphin-producing neurons were not activated by CO(2) inhalation. Endogenous opioids are related to moderate, hypercapnia-induced anesthetic effects, but, beta-endorphin-producing neurons in the hypothalamus were not activated by the CO(2) inhalation stress.