Spinal and cortical spreading depression enhance spinal cord activity.

Cortical spreading depression (CSD) has been suggested to underlie some neurological disorders such as migraine. Despite the intensity with which many investigators have studied SD in the brain, only a few studies have aimed to identify SD in the spinal cord. Here we described the main characteristic features of SD in the spinal cord induced by different methods including various spinal cord injury models and demonstrated that SD enhances the spinal cord activity following a transient suppressive period. These findings suggest that SD may play a role in the mechanisms of spinal neurogenic shock, spinal cord injury, and pain. Furthermore, we studied the effect of CSD on the neuronal activity of the spinal cord. CSD was induced via cortical pinprick injury or KCl injection in the somatosensory cortex. CSD did not propagate into the cervical spinal cord. However, intracellular recordings of the neurons in the dorsal horn of C2 segment, ipsilateral to the hemisphere in which CSD was evoked, showed a transient suppression of spontaneous burst discharges, followed by a significant enhancement of the neuronal activity. This indicates a link between a putative cause of the neurological symptoms and the subsequent pain of migraine.

Effect of pretreatment with intrathecal excitatory amino acid receptor antagonists on the development of pain behavior caused by plantar incision.

BACKGROUND: Drugs that block spinal excitatory amino acid receptor activation may prevent pain after surgery. The authors previously studied the effect of excitatory amino acid receptor antagonists after incision. In the present study, we examined the role of N-methyl-d-aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors (mGluRs) on the development of pain behavior after plantar incision. METHODS: Rats with lumbar intrathecal catheters were anesthetized with halothane. Fifteen minutes before an incision was made, drug [40 nmol MK-801; 20 nmol NBQX; or 200 nmol (+)-MCPG] or vehicle was injected intrathecally followed by an infusion of the same drug for 75 min. Withdrawal thresholds to calibrated von Frey filaments applied adjacent to the wound and response frequencies to a blunt mechanical stimulus applied directly to the wound were measured before incision and 1, 2, 4, and 6 h after incision and then once daily for 6 days. RESULTS: Preincision treatments with antagonists against the NMDA (MK-801) and group I and II metabotropic receptors [(+)-MCPG] did not inhibit the development of mechanical hyperalgesia caused by incision. Preincision treatment with the non-NMDA receptor antagonist NBQX increased withdrawal thresholds at 1 and 2 h and on postoperative day 1 compared with the vehicle group; response frequencies were reduced 1 and 2 h after incision and on postoperative day 2 (P < 0.05). In an additional group, postincision treatment with NBQX was similar to preincision treatment. CONCLUSION: Spinal NMDA and mGluR antagonists may not be useful for preventing postsurgical pain. Spinal non-NMDA receptor antagonists reduced pain behaviors, but a preventive effect using preincision treatment was not apparent.

Lumbar catheterization of the subarachnoid space with a 32-gauge polyurethane catheter in the rat.

Chronic catheterization of the subarachnoid space of rats is an important tool for intrathecal drug delivery in pharmacologic investigations of pain. We describe a technique using direct lumbar insertion of a small 32-gauge polyurethane (PU) catheter without extensive surgery. Location of the catheter was confirmed with 2% lidocaine injection 1 day later, and methylene blue injection after 7-14 days. This method improved recovery of the rat after catheter implantation and reduced neurologic complications.

Experimental arthritis in the rat does not alter the analgesic potency of intrathecal or intraarticular morphine.

UNLABELLED: To explore further the role of inflammatory processing on peripheral opioid pharmacology, we examined whether the potency of intraarticular (i.a.) or intrathecal (i.t) morphine in tests of thermal and mechanical nociception changed during the induction of experimental arthritis in the rat. Thermal nociception by i.t. morphine (3, 10, and 50 micrograms) or i.a. morphine (100, 1000, and 3000 micrograms) was assessed by means of a modified Hargreaves box ever) 28 h. Mechanical antinociception was determined for the largest applied doses of morphine using von Frey hairs. Morphine produced dose-dependent thermal antinociception after i.t. or i.a. administration: a 50% increase in maximum antinociceptive thermal response (50% effective dose) was produced by i.t. doses of 9.7 micrograms at the start and 9.1 micrograms at the end of this 28-h observational interval, whereas after i.a. administration, 50% effective dose values were 553 micrograms at the start and 660 micrograms at the end. The largest applied dose of either i.t. or i.a. morphine produced mechanical antinociception. On Day 1, the antinociceptive effect for mechanical nociception (expressed as the area under the curve of the percentage of maximal possible effect values at 0.5, 1, 2, and 4 h) was 68% for i.t. morphine 50 micrograms and 53% for i.a. morphine 3000 micrograms. Neither result differed from the corresponding area under the curve values on Day 2. Naloxone administered either i.t. or i.a. abolished the antinociceptive action of morphine given at the same site. We conclude that, although morphine has a peripheral analgesic site of action in a rat arthritis model, its potency for both i.a. and i.t. routes of administration does not change during the onset of arthritis. IMPLICATIONS: In this animal study, we showed that the administration of morphine modulates thermal and mechanical antinociception at central and peripheral sites in inflammatory pain.

Epidural analgesia with local anesthetics after abdominal surgery: earlier motor recovery with 0.2% ropivacaine than 0.175% bupivacaine.

UNLABELLED: The aim of this prospective, randomized, double-blinded study was to compare pain relief, side effects, and ability to ambulate during epidural anesthesia with ropivacaine 0.2% plus sufentanil versus bupivacaine 0.175% plus sufentanil after major gastrointestinal surgery. Epidural catheters were inserted at T8-11, and 30 microg of sufentanil with 15 mL of ropivacaine 0.75% (Group 1, n = 42) or bupivacaine 0.5% (Group 2, n = 44) was injected. General anesthesia was induced, a continuous epidural infusion (5 mL/h) was then begun with 1 microg/mL sufentanil plus ropivacaine 0.2% (Group 1) or bupivacaine 0.175% (Group 2). Postoperatively, the infusion rate was adjusted to individual requirements. Patients were also able to receive additional 2-mL bolus doses every 20 min. Demographic data (except for gender and height), analgesia, drug dosage, and side-effects, including motor blockade (Bromage score), were similar in both groups, but mobilization recovered more quickly in Group 1. Gender, age, ASA physical status, duration of surgery, and intraoperative blood loss had no effect on mobilization. We conclude that epidural analgesia is effective and safe with both regimens. There is not necessarily a correlation between the Bromage score and the desired outcome of mobilization. The ability to walk postoperatively is hastened if ropivacaine is used instead of bupivacaine. IMPLICATIONS: Regarding pain relief and side effects, epidural analgesia with ropivacaine 0.2% and sufentanil 1 microg/mL yields pain scores and pain intensity comparable to those for the well evaluated combination of bupivacaine 0.175% and sufentanil 1 microg/mL. However, earlier recovery of the ability to walk unassisted in patients receiving the combination of ropivacaine and sufentanil may result in their earlier rehabilitation.

A multimodal approach to control postoperative pathophysiology and rehabilitation in patients undergoing abdominothoracic esophagectomy.

UNLABELLED: This two-armed study was designed to determine whether recovery after esophageal resection may be improved by introducing a new multimodal approach. For 8 mo after the new approach was introduced, all patients undergoing abdominothoracic esophageal resection were studied (Group 2; n = 42). For comparison, a retrospective analysis was also conducted using the data of all patients who had undergone this operation in the 8 mo before the introduction of the new regimen, when the traditional therapy was still in use (Group 1; n = 49). All patients received an epidural catheter at the level of T6-9 before the induction of general analgesia. Afterward, Group 1 patients were operated under general anesthesia. For postoperative pain relief, a mixture of bupivacaine 1.25 mg/mL and sufentanil 1 microg/mL was administered during 5 days without titration of the quality of analgesia. Patients in Group 2 received a preoperative bolus of 10-15 mL bupivacaine 2.5 mg/mL and 20-30 microg sufentanil. After sensory block up to T4 was confirmed, general anesthesia was introduced and intraoperatively combined with a continuous infusion of 5 mL/h of a solution containing bupivacaine 1.75 mg/mL and sufentanil 1 microg/mL. Postoperatively, the epidural infusion rate was adjusted to the need of the individual patients, who were able to administer themselves additional bolus doses of 2 mL with a lockout time of 20 min. Early tracheal extubation and forced mobilization were pursued to improve recovery. Demographic data of both groups were comparable. The pain relief of Group 2 patients was superior to that of patients in Group 1. The nitrogen balance of a subgroup of nine matched pairs of patients with comparable nutritional status was less negative in Group 2 patients on Postoperative Days 1 and 2. Patients in Group 2 were tracheally extubated earlier (mean 6.7 vs 25.1 h after admission to the intensive care unit [ICU]), mobilized earlier (mean 1.2 vs 2.0 days after surgery), discharged from the ICU earlier (mean 1.7 vs 4.0 days), and fulfilled criteria for discharge from the ICU (mean 1.8 vs 4.1 days) and from the intermediate care unit earlier (4.9 vs 6.4 days). We conclude that the multimodal approach may improve recovery and thus reduce costs after abdominothoracic esophageal resection. IMPLICATIONS: Analgesia and blockade of the perioperative stress response, combined with other aspects of postoperative therapy, may improve recovery after surgery. The intensive care unit stay after esophageal resection was reduced by a new regimen (thoracic epidural analgesia, early tracheal extubation, forced mobilization). This approach may influence the cost of major surgery.

[Patient-controlled postoperative epidural analgesia. Prospective study of 1799 patients]. / Patientenkontrollierte postoperative Epiduralanalgesie. Prospektive Befunde von 1799 Patienten.

UNLABELLED: Side effects of postoperative epidural analgesia can be controlled by two strategies: Insertion of catheters into the center of the affected spinal segments and coadministration of local anesthetics and opioids. Both techniques will reduce single drug dosage. Additionally synergistic effects will result in excellent analgesia and the risk of side effects and complications will be minimized. METHODS: Between september 1995 and february 1997 the pain-service of the Klinik and Poliklinik für Anästhesiologie und operative Intensivmedizin der Westfälischen Wilhelms-Universität Münster has used this regimen to treat 1799 postoperative patients with patient-controlled epidural analgesia. All patients received an infusion of bupivacaine 0.175%, which was combined with sufentanil 1 microgram/ml in adults under the age of 70 an in children with a body weight > 30 kg. The infusion was adjusted to the individual needs of the patients by a visual analogue scale (VAS-scale: 1 = no pain; 10 = worst pain possible). Analgesia was adequate if VAS-scores were < 4 during rest and < 7 during movement and coughing. The continuous drug administration was combined with additional patient-controlled bolus doses. Postoperatively a special observation period to monitor side effects of epidural sufentanil was not defined. All patients were admitted to wards as soon as they fulfilled common criteria for discharge from the recovery room. RESULTS: Mean VAS-scores during the postoperative observation-period were within the prior defined limits. On the morning after surgery, however, a reduction in pain relief was observed and analgesia on the first postoperative day could significantly be improved after a 24-h on call pain service has been introduced. Except urinary retention side effects are rare. Probability of motor-blockade is significantly lower in patients with thoracic compared to patients with lumbar catheters. Not any patient suffered from severe complications such as sedation or respiratory depression.de

[Quality control in multimodal postoperative therapy]. / Qualitätsverbesserung durch multimodale postoperative Therapie.

Effects of anaesthesia and analgesia on postoperative morbidity and mortality remain controversial. Numerous studies have demonstrated that epidural anaesthesia and pain relief by epidural analgesia reduces perioperative stress responses and thus may reduce postoperative morbidity and mortality. In patients undergoing vascular surgery, epidural anaesthesia diminished postoperative hypercoagulability. These patients may benefit from less thromboembolic complications as well as a reduced risk of a re-operation. However, regional anaesthesia does not affect cardiopulmonary morbidity or overall mortality significantly in most clinical studies. One reason for this disappointing finding may be the missing integration of improved postoperative pain relief into general surgical care. A multimodal therapeutic approach, which consists of preoperative patient information, sufficient analgesia, early mobilisation and enteral feeding, may solve this discrepancy. Therefore, prospective controlled studies are needed to assess the influence of this perioperative approach on outcome.

[A modern concept of postoperative pain therapy]. / Ein modernes Konzept zur postoperativen Schmerztherapie.

Pain relief should be considered part of a multimodal postoperative approach. Combining patient-controlled pain therapy with other measures i.e. respiratory therapy or early mobilisation improves the outcome after surgery. In many patients adequate postoperative pain relief can be achieved by an optimal use of traditional pain management strategies. Therefore different levels of therapy should be introduced. On the first level nursing staff on surgical wards should treat pain. Patients undergoing extended surgery will need the advanced techniques of a postoperative pain service including balanced analgesia with antipyretic analgetics, patient-controlled intravenous opioids and epidural drug administration. Low dose combinations of local anaesthetics and opioids administered via thoracic epidural catheters result in excellent analgesia and provide the most effective means in improving outcome after surgery. For optimal adjustment of the patient-controlled techniques and early detection of side effects and complications nursing staff must be integrated into the pain service. Such a structured pain management program requires the training of nurses in the principles and techniques of postoperative pain treatment. Dosage of patient-controlled intravenous opioids or epidural drug combinations must be adjusted to the individual needs of the patients. Best results can only be achieved if the patient remains under observation by the pain service. This requires daily or twice daily rounds including an adequate documentation of pain relief, side effects and complications.