Stephen H. Butler

Case reports and hypothesis: A neglect-like syndrome may be responsible for the motor disturbance in reflex sympathetic dystrophy (complex regional pain syndrome-1)

Reflex sympathetic dystrophy (RSD, Complex Regional Pain Syndrome-1, CRPS-1) is a chronic pain disorder associated with autonomic dysregulation that most commonly involves a limb. In addition to pain, motor dysfunction in the involved extremity may be a significant cause of disability. To spur reassessment of underlying mechanisms and development of novel rehabilitative approaches for RSD, we propose a new hypothesis: a neurologic neglect-like syndrome may explain the motor dysfunction that occurs in a subgroup of RSD patients. This hypothesis is based on a selected series of 11 patients who underwent specific neglect testing. The etiology of neglect in RSD is not clear, but we hypothesize that changes within central nervous system (CNS) structures may occur following persistent abnormal activation of the peripheral and autonomic nervous systems, which then may result in a neglect-like syndrome. Further study is needed to verify our clinical observations and test this hypothesis.

The Effects of Postoperative Peridural Analgesia on Pulmonary Therapy and Pulmonary Complications

Effects of continuous postoperative pain relief produced by peridural block with bupivacaine on effectiveness of postoperative pulmonary therapy, incidence of pulmonary complications, and duration of convalescence were evaluated. Patients receiving morphine for postoperative analgesia served as controls. Forty patients scheduled for upper abdominal or hip-fracture operations were studied for 72 hours. They were divided into four equal groups: postoperative peridural analgesia with pulmonary therapy, peridural analgesia without pulmonary therapy, morphine analgesia with pulmonary therapy, and morphine analgesia without pulmonary therapy. Preoperative and postoperative variables compared were: chest x-rays, arterial blood gases, calculated alveolar-arterial Po2 differences (A-aDo2), vital capacity (VC), peak expiratory Bow rate (PEFR), and duration of convalescence. Patients receiving pulmonary therapy combined with either morphine or peridural analgesia postoperatively did not have a decreased incidence of atelectasis, improvement in blood-gas values, or shorter convalescence times compared with control values (no pulmonary therapy). Twelve of 20 patients in the morphine group and seven of 20 patients in the peridural analgesia group showed x-ray evidence of atelectasis 72 hours after operation. Twenty-four hours postoperatively, the morphine group had decreased arterial blood gases (Pao2 Paco2), vital capacity, and peak expiratory flow rate, and an increase in A-aDo2 compared with preoperative levels. Corresponding values in the peridural analgesia group did not reveal a significant improvement over the morphine group. The mean convalescence time of peridural analgesia patients was three days shorter than that of the patients receiving morphine (4.8 ± 0.2 vs. 7.8 ± 0.6, P < 0.005).

Event-related potential correlates of analgesia; comparison of fentanyl, acupuncture, and nitrous oxide

Abstract This study was undertaken to determine whether different analgesic treatments result in a common change in the event‐related potentials (ERP) elicited during painful dental stimulation. The effects of electrical acupuncture delivered at 2 Hz to LI‐4, the opiate fentanyl 0.1 mg i.V., and the inhalation analgesia mixture of 33% nitrous oxide in oxygen were examined in volunteers undergoing painful tooth pulp stimulation. ERPs were recorded at vertex and subjects provided reports of pain intensity. Discriminant function analysis was used to determine which subset of the pain report and ERP variables could best discriminate baseline from treatment conditions without regard to specificity of treatment. Together with pain report, amplitude of the ERP positive deflection at 250 msec was a significant indicator of analgesia across the 3 treatments. Other changes specific to the individual treatments were also observed. Since the 250 msec amplitude measure was not redundant statistically with pain report, the ERP data provided significant new information about analgesia even though pain report was a very sensitive measure. Pain report alone could account for 48% of the variance across treatments while ERP measures alone accounted for 34%.

Effects of doxepin on perception of laboratory-induced pain in man.

&NA; Beneficial effects have been observed in University of Washington Pain Clinic patients treated with tricyclic antidepressants, but such effects occur much earlier than predicted mood elevation. A laboratory investigation of pain perception was employed to test the hypothesis that doxepin, a tricyclic antidepressant, has analgesic properties. Healthy, normal volunteers were tested over a 4‐week period during which they repeatedly performed Sensory Decision Theory tasks while undergoing painful dental stimulation. Doxepin and a placebo were administered after baseline measurement for 4 weeks under double blind conditions. No significant changes due to drug administration were observed in detection threshold or sensory sensitivity indices, but response bias against reporting the stimuli as painful changed dramatically after subjects began ingesting capsules. This effect was evident in both drug and placebo groups, and it was maintained across repeated weeks of testing. These observations suggest that the instructions given patients when the drug is administered have a profound effect on pain report.

Opiate analgesia and its antagonism in dental event-related potentials: Evidence for placebo antagonism

The analgesic effects of the synthetic opiate fentanyl citrate (0.1 mg) on subjective pain reports (SPR) and late-wave event-related potentials (ERP) recorded during painful dental stimulation were examined in human subjects. Such waves have been shown to reflect the contribution of cognitive variables, such as expectancy and belief, to perception. In addition, the study was intended to demonstrate a dose-related narcotic antagonism with injection of naloxone (1.2 or 0.4 mg) or normal saline (double-blind) following IV fentanyl administration. Fentanyl reduced both ERP waveform amplitudes and SPR as have previously studied analgesic agents, such as nitrous oxide, acupuncture, and aspirin. Naloxone injection reversed both ERP and SPR changes, but surprisingly, a reversal of narcotic analgesia equal to that of 0.4 mg naloxone was seen with saline injection. By change, all subjects were health-science students or professionals who were knowledgeable in opiate pharmacology, and so placebo reversal was hypothesized. Alternatively, it was hypothesized that fentanyl cleared more rapidly than predicted, thus, producing apparent reversal. In a second experiment involving similarly knowledgeable subjects with identical procedures and testing intervals, subjects received 0.1 mg fentanyl, but no reversal injection. The fentanyl effect was constant across this time period. The data, thus support the hypothesis that the saline-induced reversal seen in experiment 1, where the subjects were knowledgeable in opiate pharmacology, was placebo opiate antagonism.

Resistance to atracurium in thermally injured rats. The roles of time, activity, and pharmacodynamics.

Thermal injury induces resistance to nondepolarizing muscle relaxants in patients. Because the mechanism of the resistance is unknown, the authors have sought to establish thermally injured rats as a suitable model for subsequent detailed studies of mechanisms. Two hundred twenty-five- to 250-g rats sustained a 30% total body surface area thermal injury while anesthetized with pentobarbital. Another group had sham injury. Animal activity was monitored both by periods of direct observation and by use of activity cages. At 10, 20, 30, 40, 60, and 90 days after injury, rats were anesthetized and ventilated and the strength of contraction of their gastrocnemius produced by supramaximal stimulation of the sciatic nerve was measured before and after a bolus of atracurium (2.0 mg/kg) was administered. The plasma concentration required to diminish contraction to 50% of the preceding value (Cp50) was determined by atracurium infusion. Animals displayed the greatest resistance to atracurium at 40 days. The Cp50 value was also greatest at this time. The protein binding of atracurium was identical for both sham and injured groups. Activity for thermally injured resistant rats and for sham animals was not different. It appears that pharmacodynamic mechanisms are involved, and inactivity and disuse atrophy are not necessary in rats for development of resistance to nondepolarizing muscle relaxants after thermal injury.

Successful pharmacologic treatment of massive atenolol overdose : sequential hemodynamics and plasma atenolol concentrations

Successful Pharmacologic Treatment of Massive Atenolol Overdose: Sequential Hemodynamics and Plasma Atenolol Concentrations Luiz G. R. DeLima;Evan D. Kharasch;Stephen Butler; Anesthesiology

Decreased cerebrospinal fluid neuropeptide-converting enzyme activity in monoarthritic rats

The activity in rat cerebrospinal fluid (CSF) of dynorphin-converting enzyme (DCE) and substance P endopeptidase (SPE) was determined in control animals and in rats with monoarthritis. Enzymatic activities were measured with specific radioimmunoassays toward the N-terminal products Leu-enkephalin-Arg6 and substance P1-7, respectively. A monoarthritis stable during weeks 2-6 post-injection was induced by injection (0.05 ml) into one joint with Freunds adjuvant. Both SPE and DCE were significantly decreased 15 days after the intraarticular injection. Despite the degree of arthritis that was sustained equally at four weeks after inoculation, both DCE and SPE were back to control levels at that time. It can therefore be concluded that arthritis from a single joint is sufficient to elicit changes in CSF convertase activities, and that these effects disappear between 2 and 4 weeks after injection, although the arthritis persists.

ANALGESIC STRENGTH OF 33 PERCENT NITROUS OXIDE: A SIGNAL DETECTION THEORY EVALUATION

Radiant heat stimulation was applied to volunteers and rating scale responses were obtained to assess the analgesic properties of 33 percent nitrous oxide. The methodology of signal detection theory was applied to the data to demonstrate that nitrous oxide reduces both sensitivity to pain and willingness to report pain. This method is superior to threshold estimation for the evaluation of analgesics.