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Biomedical subjects

D L Hammond

Publications and source records attributed to D L Hammond.

68 records · Page 4Linked to original sources
PubMed1984

Antagonism of stimulation-produced antinociception by intrathecal administration of methysergide or phentolamine.

This study examined whether the antinociception produced by electrical stimulation of medullary raphe nuclei is mediated by activation of monoaminergic neurons projecting to the spinal cord. Ninety-four sites distributed about the midline of the medulla were stimulated and their ability to produce antinociception was determined using two different analgesiometric tests. Stimulation of sites in the nuclei raphe pallidus and raphe obscurus did not produce antinociception, but rather, produced tremor and, on occasion, extensor rigidity. In contrast, stimulation at sites located in the nucleus raphe magnus and the adjacent nucleus reticularis paragigantocellularis produced antinociception, as indicated by increased tail flick latencies and decreased responsiveness to noxious pinch applied to the extremities. Intrathecal administration of saline prior to electrical stimulation of these sites did not attenuate either the elevation of tail flick latencies or the decreased responsiveness to pinch. However, intrathecal administration of 30 micrograms of either methysergide or phentolamine prior to stimulation at these same sites significantly attenuated the increase in tail flick latency and restored responsiveness to pinch. Naloxone (1 mg/kg, s.c.) did not attenuate the stimulation-produced antinociception evoked from any of these sites. These data support the postulate that the antinociceptive effect of electrical stimulation of the nucleus raphe magnus and the nucleus reticularis paragigantocellularis is mediated by activation of serotonergic and noradrenergic neurons projecting to the spinal cord. The inability of either methysergide or phentolamine alone to completely antagonize the elevation of tail flick latency further suggests that the serotonergic and noradrenergic bulbospinal systems are coactivated by electrical stimulation of these sites.

Animals↗
PubMed1984

Conjugates of dopamine and serotonin in ventriculocisternal perfusates of the cat.

The in vivo formation of acid-hydrolyzable conjugates of dopamine and of serotonin (presumably dopamine-O-sulfate and serotonin-O-sulfate) in ventriculocisternal perfusions of the cat is described. Small amounts of these amine conjugates were detected under quiescent conditions and during evoked release of the parent amines. The amounts of conjugated dopamine in perfusate were increased during and immediately after the period in which release of dopamine was evoked, but were not affected by inhibition of monoamine oxidase. In contrast, the efflux of serotonin conjugate during the evoked release of serotonin was not increased unless monoamine oxidase was inhibited. The data suggest that conjugation of amines in the CNS may be of functional importance in their disposition either under conditions of augmented release or during inhibition of oxidative deamination.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Concurrent measurement of substance P and serotonin in spinal superfusates: failure of capsaicin and p-chloroamphetamine to co-release.

This study examined the efflux of endogenous serotonin and substance P-like immunoreactive material into in vivo superfusates of the rat spinal cord under quiescent conditions and during the addition of either capsaicin or p-chloroamphetamine to the superfusate. Using a method which permitted concurrent measurement of serotonin and substance P-like immunoreactive material in the same sample of superfusate, it was found that capsaicin increased the efflux of substance P-like immunoreactive material from the spinal cord but did not alter the efflux of serotonin. Conversely, the addition of p-chloroamphetamine caused the efflux of serotonin from the spinal cord to increase, but did not affect the efflux of substance P-like immunoreactive material.

Amphetamines↗
PubMed1983

Drug-induced alterations in the efflux of 5-hydroxytryptamine and of 5-hydroxyindoleacetic acid into superfusates of the rat spinal cord.

The effect of dl-p-chloroamphetamine, fluoxetine and probenecid on the efflux of endogenous 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) into superfusates of the spinal cord of anesthetized rats was examined. Mean basal efflux of 5HT and 5HIAA was 0.27 and 15.56 ng/ml superfusate, respectively. The addition of dl-p-chloroamphetamine to the superfusate produced a dose-dependent increase in the efflux of 5HT into the superfusate, but did not increase the efflux of 5HIAA. Probenecid (200 mg/kg i.p.) increased the basal efflux of both 5HT and 5HIAA as compared to control values. When administered systemically, fluoxetine (10 mg/kg i.p. or s.c.) decreased the basal efflux of 5HIAA, but did not alter the basal efflux of 5HT as compared to control values. In contrast, when administered in the superfusate, fluoxetine produced a dose-dependent increase in the basal efflux of 5HT, but did not alter the basal efflux of 5HIAA. The release of 5HT produced by the addition of 2.5 X 10(-4) M dl-p-chloroamphetamine to the superfusate was not prevented in rats pretreated systemically with fluoxetine, although when administered in the superfusate fluoxetine inhibited the dl-p-chloroamphetamine-induced release of 5HT.

Animals↗
PubMed1981

Alterations in nociceptive threshold and morphine-induced analgesia produced by intrathecally administered amine antagonists.

Intrathecal administration of either methysergide or phentolamine hyperalgesia. This suggests that tonically active serotonergic and noradrenergic neuronal systems modulate sensitivity to nociceptive stimuli at the level of the spinal cord. Methysergide did not attenuate the analgesia induced by either 2.0 or 7.5 mg/kg morphine (s.c.), while phentolamine attenuated the analgesia induced by 2.0, but not 7.5 mg/kg morphine. These findings suggest that bulbospinal serotonergic neurons are not integral components of the neuronal circuitry which mediates opiate-induced analgesia. Noradrenergic neurons, however, appear to mediate a portion of such analgesia.

Analgesia↗
PubMed1981

Presence of conjugated 5-hydroxytryptamine in in vivo superfusates of rat spinal cord.

The presence of an acid-hydrolyzable conjugate of 5-hydroxytryptamine, presumably 5-hydroxytryptamine-O-sulfate, was demonstrated in in vivo superfusates of rat spinal cord by HPLC with electrochemical detection. In untreated rats, the concentration of the 5-hydroxytryptamine conjugate measured during the basal efflux of 5-hydroxytryptamine did not differ from that measured during the release of 5-hydroxytryptamine evoked by DL-p-chloroamphetamine. Pretreatment of the rats with clorgyline, an inhibitor of the enzyme monoamine oxidase (EC 1.4.3.4), or with probenecid did not alter the concentrations of conjugated 5-hydroxytryptamine measured during the basal efflux of 5-hydroxytryptamine, but did elevate the concentrations of conjugate measured during the evoked release of 5-hydroxytryptamine.

Animals↗
PubMed1981

Functional aspects of bulbospinal monoaminergic projections in modulating processing of somatosensory information.

Descending monoamine pathways have been shown to modulate the processing of nociceptive information. Several lines of evidence support this hypothesis: 1) stimulation of brain-stem sites by intracerebral electrodes or the local application of opiates inhibits spinal reflex activity, this effect being antagonized by intrathecal monoamine antagonists; 2) the iontophoretic administration of monoamines in the spinal cord will antagonize the discharge of dorsal horn nociceptors; and 3) the intrathecal administration of monoamines will elevate the pain threshold in the unanesthetized animal. One natural mode of activating this intrinsic circuit appears to be through the activation of small-diameter afferents. Recent evidence has shown that such somatic stimulation causes the release of 5-hydroxytryptamine and norepinephrine. The role of this system appears to be in modulating the properties of sensory processing at the spinal cord level.

5-Hydroxytryptophan↗
PubMed1980

Hypoalgesia induced by microinjection of a norepinephrine antagonist in the raphe magnus: reversal by intrathecal administration of a serotonin antagonist.

Microinjection of phentolamine in the nucleus raphe magnus produces hypoalgesia as assessed by both the tail flick and hot plate tests. The elevation of tail flick latency appears to result from activation of serotonergic raphe-spinal projections, while the elevation of hot plate latency appears to be mediated by activation of non-serotonergic raphe-spinal neurons and/or by activation of raphe neurons which project to supraspinal nuclei.

Animals↗
PubMed1980

Effects of locus coeruleus lesions on morphine-induced antinociception.

These studies were designed to examine the role of the norepinephrine-containing cells comprising the nucleus locus coeruleus (LC) in the mediation of pain perception and morphine-induced antinociception. Nociceptive threshold and morphine-induced analgesia were measured following monosodium-L-glutamate lesions of the LC and adjacent tegmentum (nucleus parabrachialis ventralis; PBV) at 17, 24 and 31 days after surgery. Nociceptive thresholds assessed by the tail flick and hot plate assays were not altered following lesions which included both the LC and PBV (Group 1) or by lesions of the PBV (Group 2) alone. Examination of lesion-induced effects on the capacity of morphine to induce analgesia revealed that damage which included both LC and PBV as well as that confined primarily to the PBV resulted in attenuation of analgesia induced by morphine. Those lesions which involved the LC altered norepinephrine content in the cortex, spinal cord and medial brain stem; however, no correlation could be demonstrated between the attenuation of morphine-induced analgesia and the changes in norepinephrine content of the brain regions examined. Thus, destruction of the LC does not appear to be responsible for the decreased effectiveness of morphine. The only region consistently damaged in both groups 1 and 2 was the ventral parabrachial nucleus. Therefore, we tentatively conclude that destruction of the PBV was responsible for the observed attenuation of morphine analgesia.

Animals↗