Anesthesia and analgesia
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Anesthesia and analgesia · Dec 1998
Intrathecal metabotropic glutamate receptor antagonists do not decrease mechanical hyperalgesia in a rat model of postoperative pain.
Spinal metabotropic glutamate receptors (mGluR) have been implicated in hyperalgesia after injury. The purpose of this study was to examine the effects of intrathecal (IT) mGluR antagonists on mechanical hyperalgesia in a rat model of human postoperative pain. The hindpaw withdrawal threshold to punctate stimulation using von Frey filaments and the response frequency to a nonpunctate stimulus applied directly to the wound were also measured. The effects of 1T (+)-alpha-methyl-carboxyphenylglycine ([+]-MCPG), (S)-carboxyphenylglycine ([S]-4-CPG), (RS)-alphacyclopropyl-4-phosphonophenylglycine ([RS]-CPPG) and L-2-amino-3-phosphonopropionic acid (L-AP3) on incision-induced mechanical hyperalgesia were examined. The withdrawal thresholds to punctate stimuli were not different from vehicle treatment after the IT administration of (+)-MCPG (100, 500 nmol), (S)4CPG (30, 100 nmol), (RS)-CPPG (100, 500 nmol), or L-AP3 (1, 30, 100 nmol). None of the IT mGluR antagonists decreased the response frequency to the nonpunctate stimulus. The largest dose of (+)-MCPG produced sufficient receptor antagonism because spontaneous nociceptive behaviors caused by the IT administration of a mGluR agonist were reduced. ⋯ Spinal metabotropic glutamate receptors antagonists, antinociceptive in some models of persistent pain, are not necessary for the maintenance of mechanical hyperalgesia in this rat model, which suggests that blockade of spinal metabotropic glutamate receptors may not be useful for the treatment of pain after surgery.
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Anesthesia and analgesia · Dec 1998
The anti-allodynic effects of amitriptyline, gabapentin, and lidocaine in a rat model of neuropathic pain.
The management of patients with neuropathic pain is challenging. There are only a few reports regarding the acute effects of the commonly used adjuvant drugs amitriptyline (AMI), gabapentin (GBP), and lidocaine (LDC) on neuropathic pain behaviors in animal models. Thus, the purpose of this study was to investigate the acute effects of AMI, GBP, and LDC on behavioral signs of mechanical allodynia and the site of action of these drugs using a rat model of neuropathic pain. Under general anesthesia with halothane, neuropathic injury was produced in rats by tightly ligating the left L5 and L6 spinal nerves. In Experiment 1, baseline mechanical allodynia data were recorded, and the animals were randomly divided into five groups: Group 1 received saline intraperitoneally (IP), Group 2 received AMI (1.5 mg/kg IP); Group 3 received GBP (50 mg/kg IP), Group 4 received an IV saline infusion for 10 min, and Group 5 received LDC (10-mg/kg IV infusion) for 10 min. Measurements of mechanical allodynia were repeated 0.5, 1, 2, and 4 h and 1, 3, and 7 days after treatment. In Experiment 2, rats were prepared similarly to the first experiment, and a single unit activity of continuous discharges of injured afferent fibers was recorded from the left L5 fascicles before and until 1 h after treatment. All animals developed neuropathic pain behavior within 7 days after surgery. All three tested drugs were effective in increasing the threshold for mechanical allodynia as early as 30 min after treatment, and the effect lasted for at least 1 h. Furthermore, AMI and LDC reduced the rate of continuing discharges of injured afferent fibers, whereas GBP did not influence these discharges. Our findings clearly demonstrate an attenuation of neuropathic pain behavior in rats treated with AMI, GBP, or LDC. Finally, the site of action of LDC seems to be primarily in the periphery, and that of GBP is exclusively central, whereas that of AMI seems to have both peripheral and central components. ⋯ In the present study, we examined the effectiveness of three drugs commonly used for the treatment of neuropathic pain. Systemic injections of amitriptyline, gabapentin, or lidocaine produced pain-relieving effects in this established model for neuropathic pain in rats, which supports their clinical use in managing patients with neuropathic pain syndromes.
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Anesthesia and analgesia · Dec 1998
Randomized Controlled Trial Clinical TrialProphylactic oral antiemetics for preventing postoperative nausea and vomiting: granisetron versus domperidone.
In this prospective, randomized, double-blinded study, we evaluated the efficacy of the oral antiemetics, granisetron and domperidone, for the prevention of postoperative nausea and vomiting (PONV) in 100 women undergoing major gynecologic surgery. Patients received either granisetron 2 mg or domperidone 20 mg (n = 50 in each group) orally 1 h before surgery. Standardized anesthetic techniques and postoperative analgesia regimens were used. Complete response (defined as no PONV and no administration of rescue antiemetic medication) for 0-3 h after anesthesia was 88% with granisetron and 52% with domperidone; the corresponding incidence for 3-24 h after anesthesia was 86% and 48% (P < 0.05). No clinically important adverse events due to the drugs were observed in any of the groups. In conclusion, the efficacy of preoperative oral granisetron is superior to that of domperidone for the prevention of PONV after major gynecologic surgery. ⋯ We compared the efficacy of granisetron and domperidone administered orally for the prevention of postoperative nausea and vomiting in women undergoing gynecologic surgery. Preoperative oral granisetron was more effective than domperidone.