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Biomedical subjects

Jon D Levine

Publications and source records attributed to Jon D Levine.

69 records · Page 4Linked to original sources

Temporal factors in the enhancement of morphine analgesia by desipramine.

Administration of desipramine, the tricyclic noradrenergic agent, for 7 days pre-operatively, had been found to potentiate postoperative morphine analgesia. In this study we investigated the necessary timing of administration of desipramine in its action to potentiate morphine analgesia. We report that the administration of desipramine for only 3 days, starting 7 days before surgery, also potentiated postoperative morphine analgesia and that the analgesia observed was not different from that in patients receiving a full 7 days of desipramine pre-operatively. The potentiation of morphine analgesia observed was most evident as a prolongation of the analgesic response. Patients who also received desipramine for only 3 days, but starting 3 days pre-operatively had an analgesic response to postoperative morphine that was the same as that in patients receiving placebo. The ability of the administration of desipramine early in the pre-operative week to interact with postoperative morphine and the lack of response when desipramine was given late in the week does not have an explanation at present. However, it may reflect the known latency in humans to the onset of the central effects of tricyclic antidepressants (TCAs).

Adult↗

Enhancement of pentazocine analgesia by clonidine.

Opiate-adrenergic interactions were investigated by studying the effect of the selective alpha 2-adrenergic agonist, clonidine, on the analgesia produced by intravenous placebo and by the predominantly kappa-opiate agonist, pentazocine, in patients with dental postoperative pain. Clonidine did not affect the pain level when administered with intravenous placebo. When administered with pentazocine, clonidine caused a statistically significant increase in pentazocine analgesia. Comparison is made to other opiate-adrenergic interactions and possible mechanisms are discussed.

Adrenergic alpha-Agonists↗

Antinociceptive and motor effects of delta/mu and kappa/mu combinations of intrathecal opioid agonists.

Interactions between selective opioid agonists acting at spinal mu-, delta-, and kappa-opioid receptors were evaluated by co-administering a low-antinociceptive dose of the selective delta-agonist, DPDPE, or the selective kappa-agonist, U50,488H, with sequentially increasing doses of the selective mu-agonist, DAMGO, intrathecally. Antinociceptive synergy (i.e., a more than additive antinociceptive effect) was observed with both combinations of opioid agonists tested. The demonstration of antinociceptive synergy suggests that the subtypes of spinal opioid receptors can act, at least in part, through a common neural circuit. Since our measure of antinociception, the Randall-Selitto paw-withdrawal test, is dependent on a normally functioning motor system, we also evaluated the effects of these same combinations of opioid peptides on motor coordination using a rotarod treadmill. A low-antinociceptive dose of DPDPE or U50,488H co-administered intrathecally, with sequentially increasing doses of DAMGO, did not worsen the decrement in rotarod performance observed with the same doses of DAMGO administered as a single agent. In fact, the low-antinociceptive dose of DPDPE significantly attenuated the decrease in rotarod performance produced when the same dose of DAMGO was administered as a single agent. The results of this study suggest that intrathecal combinations of selective mu- with both delta- or kappa-selective opioid agonists can produce antinociceptive synergy without producing an increase in motor side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Lack of effect of ephedrine on opiate analgesia.

Opiate-adrenomimetic interaction was investigated by studying the effect of the adrenomimetic agent, ephedrine, on the analgesia produced by intravenous placebo and that produced by the predominantly kappa opiate agonist, pentazocine, in patients with dental postoperative pain. Ephedrine did not significantly affect the analgesia of intravenous placebo or of pentazocine. These results contrast with earlier studies demonstrating enhancement of opiate analgesia by other adrenomimetics. Further clinical studies are needed to delineate the specificity of opiate-adrenomimetic interaction.

Drug Synergism↗

A possible indicator of functional pain: poor pain scale correlation.

We studied correlations of pain measures in patients with either inflammatory bowel disease (IBD), a disease with a clear organic cause, or irritable bowel syndrome (IBS), a functional pain syndrome in which there is little demonstrable pathology. Correlations were determined between measures on the visual analogue scale (VAS) and on the McGill Pain Questionnaire (MPQ). The VAS score and present pain intensity scale (PPI) of the MPQ correlated well in the organic IBD but correlated poorly in the functional IBS. Differences in correlation between the VAS and PPI scores in functional versus organic disease did not appear to be due to altered sensory and affective pain components. This finding is similar to what we observed in our previous study of organic and functional pain syndromes in the musculoskeletal system. Correlations between the other measures are also discussed.

Chronic Disease↗

The contributions of interpersonal conflict to chronic pain in the presence or absence of organic pathology.

This study investigated the influences of social support and interpersonal conflict on chronic pain in patients with arthritis or with myofascial disorders. Measures of social support, conflict, and pain were drawn from subscales of the McGill Pain Questionnaire, the Multidimensional Pain Inventory, the Family Environment Scale, and the Interpersonal Relationship Inventory. Patients with myofascial disorders reported significantly worse pain (sensory and affective), higher depression scores, more interpersonal conflict, and less support from others than patients with arthritis, but did not differ from them on personality traits. Also, the contributions of conflict to pain were found to depend on the nature of the chronic disorder and on the source of the conflict, i.e., significant other, family, or social network members. For patients with arthritis, less intense pain (sensory and affective) was associated with higher family conflict. Less intense sensory pain in arthritis was also associated with more punishing responses from the significant other to pain. For patients with myofascial disorders, more intense affective pain was associated with higher social network conflict. Social support did not significantly contribute to pain for either group. Thus, chronic painful disorders may differ on the influences that social relationships have on pain. The implications of these differences for treatment are discussed.

Chronic Disease↗

Altered autonomic function in patients with arthritis or with chronic myofascial pain.

Dynamic autonomic function tests (pupillary light reflex, Valsalva maneuver, and mental arithmetic) were used to evaluate autonomic function (pupil size, heart rate, and skin conductance) in patients with inflammatory arthritis or with chronic myofascial pain. Physiological responses in both groups of patients suggest concurrent increases in tonic pupillary autonomic activity (sympathetic and parasympathetic), with a relative sympathetic dominance, and a decrease in tonic parasympathetic cardiovascular activity. Furthermore, in the arthritis group, the data suggest decreased cardiovascular parasympathetic reaction and enhanced sudomotor reaction.

Arthritis↗

Differing correlations between pain measures in syndromes with or without explicable organic pathology.

We investigated the use of pain measures in chronic pain syndromes with and without explicable organic cause by correlating scores obtained from the Visual Analog Scale and from subscales of the McGill Pain Questionnaire in patients with either inflammatory arthritis or primary fibrositis. We confirmed the finding that patients with fibrositis, despite having significantly less demonstrable pathology, report more pain on a significant number of measures. In patients with arthritis, we observed large positive correlations between scores on different pain measures, supporting the hypothesis that these scores validly measure pain secondary to tissue injury. In the fibrositis group, however, significantly lower correlations, and one even strongly negative, were found between scores on different measures. We suggest that commonly used pain measures which have been shown to be valid to study patients with demonstrable pathology may be less valid for measurement of pain in patients with syndrome such as fibrositis, whose pain may be different or more complex than that of patients with explicable organic basis.

Adult↗

Sleep fragmentation in the arthritic rat.

We examined the diurnal sleep-wake patterns in the adjuvant arthritic rat. In contrast to control rats, arthritic rats lacked a normal diurnal variation in sleep and wakefulness. Thus, arthritic rats exhibited no differences in the mean number or duration of bouts of sleep and episodes of wakefulness between light and dark hours. Arthritic rats also had a marked increase in the fragmentation of their sleep manifested by an increased number of sleep bouts and episodes of wakefulness and a decrease in the duration of episodes of deep sleep recorded both during the time of maximal sleep (08.00-11.00 h) and of maximal wakefulness (20.00-23.00 h). The possibility that the experience of chronic pain causes these marked changes in sleep patterns in the arthritic rat is discussed.

Animals↗

Synergism between the analgesic actions of morphine and pentazocine.

In a double-blind, placebo-controlled study the analgesic efficacy of the combination of morphine, a mu-opiate receptor agonist and pentazocine, a kappa-opiate receptor partial-agonist was evaluated. Groups of 20 patients received either vehicle, morphine (2, 4, 8 or 16 mg), pentazocine (15, 30 or 60 mg) or a combination of morphine and pentazocine (2 mg or 4 mg and 15 mg or 30 mg, respectively). The combination of morphine and pentazocine produced a level of analgesia significantly greater than can be accounted for by simple addition of the analgesic effects of each opiate analgesic alone. We propose that the observed synergism between morphine and pentazocine is due to interaction between mu- and kappa-opioidergic components of endogenous opioid-mediated analgesia systems.

Adult↗

Desipramine enhances opiate postoperative analgesia.

In a double-blind, placebo-controlled study the analgesic efficacy of the combination of a tricyclic antidepressant and morphine was investigated. One of two tricyclic antidepressants (either amitriptyline, a relatively selective serotonin uptake inhibitor or desipramine, a relatively selective noradrenaline uptake inhibitor) or a placebo, was given for 1 week prior to surgery, followed by a single postoperative dose of morphine. Desipramine, but not amitriptyline, both increased and prolonged morphine analgesia. Neither tricyclic antidepressant reduced dental postoperative pain in the absence of morphine. We propose that desipramine enhances opiate analgesia by enhancing a noradrenergic component that contributes to endogenous opioid-mediated analgesia systems.

Amitriptyline↗

Altered electrodermal responsivity associated with clinical pain.

We used certain physiologic maneuvers to perturb the autonomic nervous system (ANS) in an attempt to detect a link between the ANS and pain. In the unperturbed state, we found no difference in the electrodermal response among normal controls, preoperative patients (increased stress without pain) and postoperative patients (increased stress and pain). The electrodermal response elicited by autonomic maneuvers was significantly attenuated in postoperative patients but not in preoperative patients or in normal control subjects.

Adolescent↗

Analgesic responses to morphine and placebo in individuals with postoperative pain.

The effects of placebo and varying doses of intravenous morphine were studied in 74 patients. All patients underwent extraction of impacted mandibular third molars. Two hours after onset of anesthesia all patients received a placebo (intravenous saline). One hour after the placebo administration each patient received either a second placebo or, 4, 6, 8 or 12 mg of morphine, double blind, via a hidden intravenous line. Pain level was evaluated 50 min after morphine administration using a visual analog scale. Pooled data from all patients produced a dose-response curve asymptotic by 8 mg. The mean pain relief following the second placebo was found to be between that obtained following hidden administration of 4 and 6 mg of morphine. When pain level reports for individuals were plotted two unexpected features appeared. First, no patient reported complete relief, even at the highest dose of morphine (12 mg). Second, pain level reports 50 min following each dose of morphine tended to be in two clusters. Within each cluster the average pain was independent of the dose of morphine administered. However, in groups receiving progressively higher doses of morphine, the percentage of patients within the low pain level cluster increased. These latter observations are most consistent with the concept that there is a step component for narcotic analgesia.

Adolescent↗