D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats.

BACKGROUND: Approximately half of all patients who undergo surgery develop postoperative pain, the mechanisms of which are not well understood by anesthesiologists. D2-like receptors in the descending dopaminergic pathway play an important role in regulation of pain transmission in the spinal cord. Impairment of inhibitory neurons in the spinal cord is suggested as part of the mechanism for neuropathic pain, which is one component of postoperative pain. The purpose of this study was to investigate whether impairment of D2-like receptors in the descending dopaminergic pathway in the spinal cord is involved in the decreased postoperative nociceptive threshold in rats. METHODS: Male Sprague-Dawley rats (250-300 g) were anesthetized with sevoflurane and an intrathecal (IT) catheter was implanted. Six days later, a plantar incision was made. On the following day, saline, a D2-like receptor agonist (quinpirole), or a D2-like receptor antagonist (sulpiride) was administered intrathecally. Thermal and mechanical nociceptive responses were assessed by exposure to infrared radiant heat and the von Frey filament test before and after plantar incision. RESULTS: Plantar incision decreased both thermal latency and the mechanical nociceptive threshold. IT administration of quinpirole inhibited the nociceptive responses induced by plantar incision, but sulpiride had no effect. CONCLUSION: A D2-like receptor agonist had antinociceptive effects on the hypersensitivity response triggered by a surgical incision, but a D2-like receptor antagonist had no effect on this response. These results suggest that impairment and/or modification of D2-like receptors in the descending dopaminergic pathway in the spinal cord is not involved in the postoperative decrease in nociceptive threshold.

Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) from spinal microglia is crucial for aberrant nociceptive signaling in several pathological pain conditions, including postoperative pain. We assess the contribution of spinal microglial activation and associated BDNF overexpression to the early post-incisional nociceptive threshold. METHODS: Male Sprague-Dawley rats were implanted with an intrathecal catheter. A postoperative pain model was established by plantar incision. Thermal and mechanical nociceptive responses were assessed by infrared radiant heat and von Frey filaments before and after plantar incision. Rats were injected intrathecally the microglial activation inhibitor minocycline before incision, 24 h after incision, or both. Other groups were subjected to the same treatments and the L4-L5 spinal cord segment removed for immunohistochemical analysis of microglia activation and BNDF expression. RESULTS: Plantar incision reduced both thermal latency and mechanical threshold, indicating thermal hypersensitivity and mechanical allodynia. Minocycline temporally reduced thermal withdrawal latency but had no effect on mechanical withdrawal threshold, spinal microglial activity, or dorsal horn BDNF overexpression during the early post-incision period. CONCLUSION: These results suggest that spinal microglia does not contribute substantially to post-incisional nociceptive threshold. The BDNF overexpression response that may contribute to postoperative hyperalgesia and allodynia is likely derived from other sources.

Efficacy of intrathecal esmolol on heat-evoked responses in a postoperative pain model.

Perioperative tachycardia and hypertension are often treated with esmolol, a short-acting ß1-adrenoceptor antagonist. Besides its cardiac effect, esmolol is reported to exert antinociceptive effects. This study examined the efficacy of intrathecal (IT) esmolol on pain responses in a postoperative pain model. Male Sprague-Dawley rats (250-300 g) were anesthetized with sevoflurane and an IT catheter was implanted. Six days after catheter implantation, a postoperative pain model was established by plantar incision under sevoflurane anesthesia. Withdrawal latencies were assessed by applying a focused radiant heat source before plantar incision; 1 day after the incision (before esmolol administration); and 5, 10, and 15 minutes after bolus administration of IT esmolol. Plantar incision produced hypersensitivity in the postoperative pain model expressed as decreased withdrawal latency to heat stimulation (before incision: 13.9 ± 0.29 seconds and 1 day after incision: 6.3 ± 0.26 seconds). These decreased latencies caused by incision were significantly increased by esmolol administration (40 µg, 80 µg) at 5 minutes (10.7 ± 1.16 seconds, 10.5 ± 1.16 seconds). No postoperative antinociceptive effects of esmolol were observed at 10 or 15 minutes. IT administration of esmolol produced antinociceptive effects of short duration in a rat postoperative pain model. These results suggest that IT esmolol could offer a new strategy for managing perioperative pain, although an alternative approach is necessary to lengthen the duration of the analgesia.

Mast cell stabilization promotes antinociceptive effects in a mouse model of postoperative pain.

BACKGROUND: Nerve injury and consequent inflammatory responses produced by surgical incision result in a complicated pain status which still affects half of all surgical patients. Therefore, it is essential for anesthesiologists to identify the mechanisms of postoperative pain. Mast cells are resident cells of connective tissue and the mucosa that participate in the immune response. Degranulation of mast cells is involved in the development of postoperative pain and can be induced by surgical incision. The aim of this study was to investigate whether stabilization of mast cells causes an antinociceptive effect in a mouse model of postoperative pain. METHODS: Postoperative pain was induced by making an incision in the hind paw of BALB/c mice. The mast cell membrane stabilizer cromoglycate (200 µg/20 µL) was injected before incision of the paw, and postoperative pain responses were measured by assessing guarding behavior, withdrawal threshold to mechanical stimuli, and latency of heat pain behavior 1, 2, and 7 days after the incision. RESULTS: The incision produced guarding pain, mechanical allodynia, and heat hypersensitivity. Cromoglycate decreased the guarding pain score (day 1) and the withdrawal threshold to mechanical stimuli (days 1, 2, and 7). However, the withdrawal latency to heat was not affected by cromoglycate treatment. CONCLUSION: Cromoglycate significantly attenuated the pain response expressed as guarding pain and mechanical allodynia in a mouse model of postoperative pain. Thus, mast cell activation is likely a mechanism of postoperative pain and is an interesting target for the development of new therapies.

Perioperative infusion of dexmedetomidine at a high dose reduces postoperative analgesic requirements: a randomized control trial.

PURPOSE: We hypothesized that a high dose of dexmedetomidine (1 µg/kg/h) could reduce postoperative analgesic requirements of patients. METHODS: This was a prospective, randomized, double-blind, placebo-controlled study carried out in Tohoku University Hospital. Thirty-two patients who underwent open gynecological abdominal surgery were randomly divided into a control (group C) and a dexmedetomidine group (group D). In both groups of patients, an epidural catheter was put in position prior to the induction of anesthesia, and continuous epidural infusion was started using a patient-controlled epidural analgesia (PCEA) pump. During the induction of anesthesia, group D patients received a loading dose of dexmedetomidine (1 µg/kg over 10 min), followed by a continuous infusion at a rate of 1 µg/kg/h. The patients in group C received a volume-matched infusion of normal saline as placebo. Consumption of PCEA bolus (local anesthetics) during the first postoperative 24 h, postoperative pain scores, and side effects related to the use of dexmedetomidine were recorded. RESULTS: Dexmedetomidine (1 µg/kg/h) significantly reduced PCEA bolus consumption [15.9 ± 6.5 (group C) vs. 5.3 ± 5.0 ml (group D); P = 0.0001] and postoperative pain scores. The infusion of dexmedetomidine produced no serious side effects, such as hemodynamic changes. CONCLUSIONS: Among this small patient cohort, perioperative infusion of dexmedetomidine (1 µg/kg/h) resulted in antinociception without severe side effects. These results suggest that this method could be of interest with respect to improving postoperative pain status.

Transcutaneous PCO2 monitors are more accurate than end-tidal PCO2 monitors.

PURPOSE: The accuracy of monitors for measuring transcutaneous PCO2 (TcPCO2), end-tidal PCO2 (EtPCO2), and nasal EtPCO2 was evaluated. METHODS: The measuring devices included a TcPCO2 monitor (TCM3; Radiometer Trading), an EtPCO2 monitor (Ultima; Datex-Ohmeda), and a nasal EtPCO2 monitor (TG-920P; Nihon Kohden). The sensor electrode of the TCM3 TcPCO2 monitor was applied to the skin of the subject's upper arm. A sampling tube attached to the proximal end of the tracheal tube was connected to the Ultima EtPCO2 monitor. The miniature sensor of the TG-920P nasal EtPCO2 monitor was attached to the nostril. The values obtained were compared with direct measurements of arterial PCO2 (PaCO2) obtained by means of an ABL700 blood gas analyzer (Radiometer Trading) in surgically treated patients. The means +/- 2 SD of the differences between variables were calculated. RESULTS: The TcPCO2 monitor (0.19 +/- 4.8 mmHg, mean +/- 2-SD) was more accurate than the EtPCO2 monitor (-4.4 +/- 6.5 mmHg, mean +/- 2-SD) in patients receiving artificial ventilation via an endotracheal tube and the TcPCO2 monitor was also more accurate than the nasal EtPCO2 monitor (-6.3 +/- 9.8 mmHg, bias +/- 2-SD) in patients breathing spontaneously. CONCLUSION: We found that the TcPCO2 monitor was more accurate than the EtPCO2 or nasal EtPCO2 monitor in surgically treated patients.

Recovery profiles from dexmedetomidine as a general anesthetic adjuvant in patients undergoing lower abdominal surgery.

BACKGROUND: Dexmedetomidine induces less change in hemodynamic values during the extubation period. This drug may be useful in anesthetic management requiring smooth emergence from anesthesia. We sought to determine the effects of co-administration of dexmedetomidine on the recovery profiles from sevoflurane and propofol, which usually provide safe and rapid recovery when administered alone. METHODS: Sixty patients undergoing lower abdominal surgery were randomly divided into four groups according to the anesthetic to be administered; namely, sevoflurane (group S), propofol (group P), both sevoflurane and dexmedetomidine (group SD), or propofol and dexmedetomidine (group PD) as maintenance general anesthetics. After induction, anesthesia was maintained with sevoflurane (0.6%-1.5%) in group S, propofol (2-5 mg/kg/h) in group P, sevoflurane and dexmedetomidine (1 microg/kg over 10 min followed by 0.4 microg/kg/h until the end of surgery) in group SD, and propofol and dexmedetomidine in group PD with continuous epidural infusion. Bispectral Index values were maintained within 45 +/- 5 by changing the concentration of sevoflurane or the infusion rate of propofol in all groups. The time between the interruption of maintenance general anesthetics and eye opening was measured. Postoperative cognitive function was evaluated using the Short Orientation Memory Concentration Test. RESULTS: The time to eye opening of groups S (8.5 +/- 2.5 min, mean +/- SD; n = 15) and SD (12.0 +/- 3.3 min) were comparable, whereas that of group PD (21.7 +/- 7.1 min) was longer than that of group P (11.0 +/- 4.4 min). The time to eye opening of group PD was significantly (P < 0.001) longer than those of the other three groups. The scores of Short Orientation Memory Concentration Test between groups S and P were similar and were not changed by co-administration of dexmedetomidine. CONCLUSION: When co-administered with dexmedetomidine, sevoflurane produced a shorter time to eye opening than propofol. Postoperative cognitive function was not affected by dexmedetomidine administration. These results suggest dexmedetomidine may delay recovery when given as an adjuvant to propofol during total i.v. anesthesia.