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Biomedical subjects

C R Chapman

Publications and source records attributed to C R Chapman.

At least 19 recordsLinked to original sources
PubMed1992

Psychological aspects of postoperative pain control.

This article examines the biological basis of emotional distress during postoperative pain, discussing the causal links between tissue injury and the mechanisms of centrally mediated emotional arousal. Neurologic signals from injured tissues induce spinoreticular transmission and extensive processing in limbic brain. Pain, as an emotion, shares central noradrenergic mechanisms with vigilance, a biologically important process. The emotional dimension of postoperative pain corresponds to perceived threat. Injury-induced activation of central noradrenergic mechanisms equips the patient for "fight or flight" just as in nature it equips a wounded animal for self-preservation actions. Although the brain chemistry of emotion prepares the postoperative patient to undertake some sort of survival-directed activity, most hospital settings do not permit patients to cope for themselves. This biologically mandated need to cope with injury has no avenue for expression. Several basic concepts from clinical psychology apply to the management of patients after surgery: Control, coping and self-efficacy. In light of the psychobiological nature of emotion in postoperative pain, they explain the benefits of therapies that encourage self-control such as patient controlled analgesia (PCA). PCA changes the role of the postoperative patient from passive to active, permitting patients in pain to cope actively for themselves. Moreover, it demonstrates that an integration of technological advances with psychological principles can improve patient satisfaction with care delivery.

Adaptation, Psychological↗
PubMed1991

Patient-controlled analgesic administration. A comparison of steady-state morphine infusions with bolus doses.

The authors have shown previously that bone marrow transplant (BMT) patients who self-administered bolus doses of morphine gained equal oral mucositis pain relief while using less drug compared with similar patients receiving morphine by staff-controlled continuous infusion. In a follow-up study they compared the efficacy and side effects of morphine in two groups of marrow transplant patients who controlled their own analgesic administration either by conventional bolus-dose, patient-controlled analgesia (PCA) or by adjusting the rate of continuous morphine infusion to increase or decrease their plasma morphine concentration. Patients controlling their morphine infusion rates (pharmacokinetically based patient-controlled analgesia [PKPCA] group) obtained more relief from oral mucositis pain than did patients using conventional PCA. Patients in the PKPCA group used more morphine than PCA patients and achieved superior pain relief without significant increases in side effects (e.g., nausea, mood changes, sedation). The authors conclude that PKPCA improves the management of prolonged, severe pain in marrow transplant patients and that this approach to patient-controlled analgesia may be useful in other types of persistent pain.

Adult↗
PubMed1991

Concentration-related effects of morphine on cognition and motor control in human subjects.

Morphine and other opioid analgesics may interfere with normal cognition and motor function when the drugs are used for long-term treatment of pain. We used individually tailored steady-state drug infusions to identify the nature and extent of cognitive and motor effects of the mu-receptor-selective opioid morphine in healthy volunteers. The tailored infusions allowed evaluation of cognitive and motor effects at three sequential, constant plasma concentrations of morphine in each subject. Compared with functional assessments obtained in a separate saline infusion day, infusions of morphine to plasma concentrations in the usual therapeutic range for analgesia caused significant impairments of some but not all elements of cognitive and motor function. The time needed to encode and process serially presented verbal information increased and the ability to maintain low consistent levels of force decreased during the morphine infusion. We also assessed verbal recall 3 hours after the morphine and saline infusions. Delayed recall of information presented during the morphine infusion was significantly impaired. Our results demonstrate that morphine can interfere with cognitive and motor performance at plasma drug concentrations within the usual therapeutic range.

Adult↗
PubMed1990

Profiles of opioid analgesia in humans after intravenous bolus administration: alfentanil, fentanyl and morphine compared on experimental pain.

This report examines the relationship of plasma drug concentration to analgesic effect following bolus doses of alfentanil, fentanyl and morphine and assesses individual differences in analgesic response among volunteers. We predicted that the 3 opioids would yield disparate analgesic profiles because their physicochemical and pharmacokinetic characteristics differ. Ten healthy volunteers received intravenous bolus doses of either alfentanil, fentanyl, morphine or normal saline on different days. We stimulated their teeth electrically and measured brain evoked potential (EP) and pain report (PR) repeatedly over 2 h to assess analgesic effect. Concurrently, we drew 18 blood samples to assess opioid plasma concentrations during the test period. The relationship between opioid plasma concentration and analgesic effect was well defined for alfentanil but ambiguous for morphine. Fentanyl exhibited a marked hysteresis. We observed noteworthy individual differences in analgesic response with all 3 drugs but these differences were greatest for morphine and least for alfentanil. Inter- and intrasubject variability in analgesic response across drugs is related to the physicochemical properties of the drugs tested.

Adult↗
PubMed1990

Steady-state infusions of opioids in human volunteers. I. Pharmacokinetic tailoring.

We report a method for controlling and adjusting plasma opioid concentration to preselected target values in individual human subjects in order to study analgesic and other effects of opioids at steady state. The method employs a computer-controlled infusion pump and an algorithm that utilizes individual subject pharmacokinetic parameters predetermined with tailoring bolus opioid doses. We used this approach to produce 3-step increases in plasma concentrations of alfentanil, fentanyl and morphine in each of 15 subjects. We maintained each plasma concentration plateau for 70 min, measured plasma opioid concentrations achieved during the infusions and analyzed the results for bias and precision of the individually tailored infusions. Our results show that pharmacokinetically tailored opioid infusions produce stable plasma opioid concentrations within 10 min for alfentanil and morphine; with each drug overall prediction error was 20% or less. Fentanyl was somewhat more difficult to control by this method than were the other 2 opioids. We conclude that individual tailoring of opioid infusions minimizes the impact of individual pharmacokinetic differences on achieving preselected plasma opioid concentrations and provides an accurate means of controlling steady-state drug concentrations for studies of concentration-effect relationships and comparisons of side-effect intensities produced by equianalgesic plasma opioid concentrations.

Adult↗
PubMed1990

Steady-state infusions of opioids in human. II. Concentration-effect relationships and therapeutic margins.

We used computer-controlled individually tailored infusions to study relationships between plasma drug concentration and opioid effects, and to evaluate the therapeutic margins of alfentanil, fentanyl and morphine in human subjects. In order to compare the 3 drugs, we infused each opioid to 3 different steady-state target plasma concentrations during separate 8 h test periods so that concentration-effect curves could be defined for each opioid and subject. Dental electrical stimulation produced a consistent degree of baseline experimental pain, and we measured the influence of increasing plasma opioid concentrations on pain intensity and the magnitude of pain-related evoked potentials. We also quantified ventilatory function and subjective side-effects during baseline (no drug), at the 3 target plasma concentrations with each drug. Finally, we measured actual plasma opioid concentrations during each phase of the infusion period. This procedure allowed us to calculate for each opioid the plasma concentration required to produce a 50% decrease in reported pain intensity and evoked potential amplitude (IC50). Subsequent calculation of side-effect magnitudes at the analgesic IC50s permitted direct comparisons of therapeutic margins between alfentanil, fentanyl and morphine. We found a robust relationship between plasma drug concentration and analgesic, ventilatory, and subjective-effect magnitudes for each opioid in this study. We conclude that the magnitudes of individual side-effects associated with equianalgesic, steady-state plasma concentrations of these 3 mu receptor-selective opioids do not differ across drugs.

Adult↗
PubMed1989

Prolonged morphine self-administration and addiction liability. Evaluation of two theories in a bone marrow transplant unit.

The technology for patient intravenous self-administration of morphine has been successfully implemented in postoperative and other clinical settings and can be used with terminal patients who experience pain. The question of whether patients who use such instrumentation will be vulnerable to over-medication or development of addiction has not been addressed. This report reviews two competing theories that bear upon this question and tests their predictions about self-administration of morphine for pain relief using data obtained from patients in a bone marrow transplant unit. The first, Opponent Process Theory, predicts escalating drug use and the development of addictive behavior in patients who self-administer morphine. The second, Control Theory, predicts that patients will self-regulate pain effectively by administering morphine without developing problems of medication abuse or addiction. Patients self-administering morphine for 2 weeks were compared to controls who received the drug via routine staff-controlled continuous infusion procedures. Self-administering patients used significantly less morphine than controls and still achieved the same amount of pain control; moreover, they terminated drug use sooner than controls. The predictions based upon Opponent Process Theory were not supported in these marrow transplant patients, but Control Theory accounted well for the outcomes. These results support the assumption that self-administration of opioids in a medical setting does not put patients at risk for over-medication or addiction.

Adult↗
PubMed1989

Assessment and management of donor pain following marrow harvest for allogeneic bone marrow transplantation.

We studied the time course and intensity of pain of multiple bone marrow aspirations in 30 healthy adult marrow donors receiving acetaminophen with codeine for analgesia immediately after marrow harvesting for allogeneic bone marrow transplantation. Upon discharge, donors were supplied with acetaminophen (315 mg) plus codeine (30 mg) tablets and instructed to use one or two tablets up to every 4 h as needed for pain control. Donors used analgesic medication for a mean (+/- SE) of 3.3 +/- 0.5 days (range = 1-13 days) and reported less than complete pain relief. Subjects reported more pain at time of medication than between doses, indicating that the analgesic was at least partially effective. Male donors tended to report more pain and use more analgesic than did females. We conclude that donors self-regulate their analgesic usage to achieve maximal relief and that incomplete relief with acetaminophen plus codeine may be due to limited efficacy of this analgesic preparation. Our findings suggest that donor pain management may be improved by use of more powerful analgesics.

Acetaminophen↗
PubMed1986

Comparison of short-latency trigeminal evoked potentials elicited by painful dental and gingival stimulation.

Painful stimulation of tooth pulp and of the maxillary gingiva was undertaken in 16 volunteers. Short-latency evoked potentials (15-50 msec) were recorded over 800 trials in each case at F3-P3 of F4-P4, and the resultant averaged wave forms were compared. The gingival wave was distinct in all subjects and could be averaged across subjects while the dental waves were either noise or very inconsistent over subjects. Averaging of the dental wave forms across subjects yielded an uninterpretable result. It was clear that dental evoked potentials could not be recorded at the sites. These findings could be explained by either or both of two hypotheses: dental afferents are predominantly small fiber, nociceptive end organs that conduct more slowly than soft tissue afferents whereas gingival stimulation activates both large and small fiber populations; and dental representation in somatosensory cortex is different and phylogenetically more primitive than that of neighboring soft tissue. Therefore, the location of the generator sites in cortex and the orientation of the dipole may be different for dental than for gingival wave forms.

Adult↗
PubMed1986

Dose effects of alfentanil in human analgesia.

Alfentanil, a rapidly acting opioid, was given in subanesthetic doses to 10 subjects in a laboratory setting. Analgesia was assessed from the subjects' responses to painful dental stimulation. A subjective pain report (PR) and brain evoked potential (EP) amplitude were obtained repeatedly before and after injection on each of 4 testing days, on which the following intravenous doses were administered: 0 (saline solution), 5, 10, and 15 micrograms/kg. Significant dose effects were observed for EP amplitude during but not beyond the distributional t1/2 of the drug, but significant effects on the PR extended beyond this time point. Mean volume of distribution, total body clearance, and distribution t1/2 did not differ significantly across the doses of alfentanil. Strong correlations between each effect measure and plasma drug concentration were observed at all doses and were significant at P less than 0.01. The EP scores tracked the distribution of alfentanil very closely, but the correlation between EP amplitude and plasma alfentanil concentration was lower during the elimination phase. In contrast, the PR effects closely tracked the elimination of alfentanil but not its distribution. These findings suggest that EP amplitude and the PR represent two different central effects in opioid analgesia.

Adult↗
PubMed1986

Evoked potentials as correlates of pain and pain relief in man.

This contribution reviews the practical applications of evoked potentials (EPs) in the evaluation of experimental studies on analgesic intervention in humans. It is also intended as an introduction to EP methodology, its possibilities, and its limitations, for all fellow researchers working in other fields.

Acupuncture Therapy↗
PubMed1985

Stimulus intensity and inter-stimulus interval effects on pain-related cerebral potentials.

The inter-relationship between stimulus intensity and inter-stimulus interval (ISI) on pain-related evoked vertex potentials was studied. Sixteen subjects were tested with 4 stimulus intensities at 4 different ISIs forming 16 averaged event-related potentials for each subject. Data were analyzed in 2 ways: first by multiple regression analysis of peak-to-peak amplitudes and secondly by single-trial analysis for each subject based on a linear model employing principal component loadings as basis functions, from which were derived separate time-dependent functions describing the contributions of intensity and ISI. Peak-to-peak amplitudes of the averaged waves increased with increases in either intensity of ISI. There were no significant interactions. However, single-trial analysis revealed subtle, but consistent, differences in the peak latencies between stimulus and ISI components, suggesting that the components arise from distinct sources.

Adolescent↗
PubMed1985

Pain measurement: an overview.

The practice and theoretical basis of pain measurement is reviewed and critically examined in the areas of animal research, human subjects laboratory investigation and clinical study. The advantages and limitations of both physiological and behavioral methods are discussed in each area, and subjective report procedures are evaluated in human laboratory and clinical areas. The need for procedures that bridge these areas is emphasized and specific issues are identified. Progress in the technology of pain measurement over recent decades is reviewed and directions for future work are suggested.

Animals↗
PubMed1985

Peak latency differences in evoked potentials elicited by painful dental and cutaneous stimulation.

Long-latency evoked potentials (EPs) (50-400 msec) have been obtained from humans during both noxious stimulation of tooth and cutaneous sites in studies of pain and analgesic states. This study investigated whether EPs elicited by tooth and lip stimulation differed in peak latency and whether EPs obtained during painful cutaneous stimulation showed increasing peak latency values with increased conduction distance. Twelve volunteers received painful electrical stimulation at four sites: tooth, lip, thumb, and toe in counterbalanced orders. Evoked potentials recorded at vertex were summation averaged over 128 trials. Multivariate stepwise discriminate analysis was used to determine whether any of the peak latencies of the event-related potentials differed across stimulation sites. No significant latency differences were observed across lip, thumb or toe at any of the major peaks. Since peaks of these EPs did not vary in latency with conduction distance, they appear to reflect processing at higher levels rather than sensory transmission. The negative 140 msec peak of the dental waveform occurred significantly later than the same peak at cutaneous sites.

Adult↗