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Biomedical subjects

M J Hoffert

Publications and source records attributed to M J Hoffert.

17 recordsLinked to original sources

Transnasal butorphanol in the treatment of acute migraine.

We studied transnasal butorphanol (Stadol NS) for pain relief during acute migraine in a multicenter, randomized, double-blind, placebo controlled trial using ambulatory patients at 10 geographically diverse headache centers. Patients were volunteer adults diagnosed with migraine with or without aura by International Headache Society criteria. One hundred fifty-seven patients completed the study. We treated the pain of one headache in each patient with either transnasal butorphanol (n = 107) or transnasal placebo (n = 50). Pain relief, pain intensity, nausea, vomiting, and effect on function were measured periodically. Adverse experiences were documented. Global assessments were made at follow-up. With butorphanol, migraine pain was reduced from moderate, severe, or incapacitating to slight or absent for 35 patients (33%) within 30 minutes, for 50 patients (47%) within 1 hour, and for 76 (71%) within 6 hours, compared to 2 (4%), 8 (16%) and 15 (30%) respectively for placebo. Side effects were prominent, though confounded by the migraine. The most common side effects, compared to placebo, were dizziness (58% vs 4%), nausea and/or vomiting (38% vs 18%), and drowsiness (29% vs 0%). We conclude that transnasal butorphanol is a useful analgesic for the pain of acute migraine. Its prominent side effects and low self reinforcement rate may limit its usefulness in some patients, while increasing its appropriateness for others.

Acute Disease↗

Treatment of migraine: a new era.

Current research has refuted the vascular theory of migraine. New insights into the phenomenon of migraine are leading to alternative treatments. Sumatriptan is the first of many new drugs that will augment the treatment of migraine. High cost may limit the use of some new drugs.

Humans↗

Spontaneous activity of cat spinal ganglion neurons in vivo.

Recordings were made from L4-S1 spinal ganglion neurons of anesthetized cats while their associated dorsal root and the sciatic nerve were left intact, locally anesthetized, or locally anesthetized and sectioned. In all three experimental conditions spontaneous discharges were recorded. These discharges occurred in the absence of any electrical stimulation of the dorsal root or sciatic nerve, and were not due to peripheral exploration of receptive fields or sustained firing in joint or muscle afferents. The spontaneous discharges were relatively rhythmic, and their firing frequency ranged from 5 to 100 impulses per s. Interactions between spontaneous and electrically evoked discharges were observed that depended on the impulse's frequency of firing. High frequency discharges always abolished low frequency impulses regardless of whether these latter were spontaneous or evoked. Extra spikes and postspike events that followed impulses evoked by stimulation of the dorsal root or sciatic nerve were also recorded from some spinal ganglion neurons. These results suggest that spontaneous discharges may originate within the spinal ganglion itself, and that they can occur under normal circumstances.

Action Potentials↗

Polypharmacy in a headache centre population.

In this paper we report the prevalence of self-medication and polypharmacy in our patient population at the John R. Graham Headache Centre at the Faulkner Hospital, Boston. One hundred fifty patients were interviewed when they called the Headache Centre and spoke to a triage nurse. A significantly higher number of women than men called in for triage counselling. Sixty-nine percent of the patients reported taking non-Headache Centre medications, either prescribed or over the counter (OTC); 39% of the patients took pain medications. Thirty-one different medications were named by patients for a mix of diagnoses.

Adult↗

The neurophysiology of pain.

Elucidating the details of the changes of neural function associated with chronic pain would do more than expand our knowledge of the neurophysiology of pain. It would also help us understand the relationship of nociception to pain both in normal and pathologic conditions. Perhaps most important, it would help us more intelligently to develop treatments to reverse these pathologic changes and thus treat chronic pain more effectively.

Central Nervous System↗

Demonstration of thyrotropin-releasing hormone immunoreactivity in neurons of the mouse spinal dorsal horn.

Thyrotropin-releasing hormone-like immunoreactivity was demonstrated in neurons within the superficial laminae (I, II, III) of the mouse spinal dorsal horn by light-microscopic peroxidase immunocytochemistry. The immunoreactivity was distributed in a narrow dorsoventral band that enclosed the substantia gelatinosa (lamina II), with a higher concentration along the lamina II/III border. At present, the functional significance of these neurons is unknown. Their existence within the substantia gelatinosa suggests a role in sensory information processing.

Animals↗

Intraspinal connections of dorsal column postsynaptic neurons in the cat--a physiological analysis.

Dorsal column postsynaptic (DCPS) neurons in the dorsal horn of the spinal cord have been identified by antidromic stimulation and intracellularly recorded in anesthetized cats. In about one-half of the cells, the antidromic stimulus evokes only an antidromic potential. This potential sometimes has an atypical shape due to penetration-induced depolarization. Atypical potentials are converted into typical antidromic spike potentials after intracellular injection of hyperpolarizing current. In the other one-half, the antidromic potentials are followed by postsynaptic activity. Intracellular analysis indicates that this postsynaptic activity is generated largely by activation of the intraspinal collaterals of A-beta primary afferents that are ascending the dorsal columns. Part of this postsynaptic activity has been produced monosynaptically. Polysnaptic responses are also evident; these are thought to be initiated by A-beta axons, desending axons from neurons in the dorsal column nuclei, or the local collaterals of the DCPS axons themselves. The results indicate that the DCPS system is nonlemniscal in nature and may be involved in those pain modulation systems that are activated by A-beta afferents.

Action Potentials↗

Serotoninergic axonal contacts on identified cat spinal dorsal horn neurons and their correlation with nucleus raphe magnus stimulation.

This study examined the distribution of serotoninergic (5-HT) immunoreactive axonal contacts on spinal laminae I and II neurons by combining the intracellular horseradish peroxidase (HRP) method with immunocytochemistry. In addition, the 5-HT distribution was correlated with effects produced by electrical stimulation within the nucleus raphe magnus (NRM). Responses of lamina I neurons and lamina II stalked cells to noxious stimulation were markedly suppressed during NRM stimulation. In contrast, responses of nociceptive lamina IIa islet or non-nociceptive lamina IIb islet cells remained unchanged during nucleus raphe magnus stimulation. These inhibitory influences were positively correlated with the distribution of 5-HT immunoreactive contacts on these neurons. Nociceptive lamina I neurons and lamina II stalked cells received a significantly greater number of contacts (average of 74 and 63, respectively) than either nociceptive lamina IIa islet or non-nociceptive lamina IIb islet cells (average of 25 and eight contacts, respectively). Irrespective of cell type, most 5-HT contacts occurred on dendritic shafts rather than spines. These data reveal a differential distribution of 5-HT contacts on neurons in spinal laminae I and II, and indicate that at least a portion of the NRM modulation of dorsal horn neuronal activity is serotoninergic and concentrated on the dendritic shafts of nociceptive lamina I neurons and lamina II stalked cells.

Animals↗

The morphology of dorsal column postsynaptic spinomedullary neurons in the cat.

Dorsal column postsynaptic ( DCPS ) spinomedullary neurons from the cat's lumbosacral enlargement were identified by antidromic stimulation of the cervical dorsal columns and stained intracellularly with horseradish peroxidase. The cell bodies were located in laminae III-IV. Their dendritic arbors were elongated rostrocaudally but narrow mediolaterally. On the average, the arbors were X 5 longer than they were wide. Most of the neurons had nearly all of their dendrites in laminae III-IV and some of the neurons had, in addition, a considerable amount of dendritic surface area in lamina V. Only one neuron had more than a very small amount of dendritic surface area dorsal to lamina III. Seven of the neurons had unmyelinated axon collaterals that arborized extensively and issued varicosity-bearing terminal branches in laminae III-V, both within and beneath their dendritic territories. All of the neurons were excited by myelinated, low-threshold mechanoreceptors. Since the rostrocaudally elongated and mediolaterally narrow dendritic arbors of DCPS neurons are in register with the laminae III-IV terminal distributions of myelinated, low-threshold mechanoreceptors, it is probable that this excitation arises from a monosynaptic and topographically discrete innervation. About one-half of the DCPS neurons were also excited by noxious stimuli. It is probable that this excitation is accomplished by a polysynaptic pathway since DCPS dendritic arbors and nociceptor terminal distributions are largely or completely separate.

Afferent Pathways↗

Immunocytochemical identification of serotonin axonal contacts on characterized neurons in laminae I and II of the cat dorsal horn.

Serotonergic pathways from brainstem to spinal cord play an important role in the modulation of pain perception. To establish where that modulation occurs, we examined serotonin-immunoreactive axonal contacts on individually characterized laminae I and II dorsal horn neurons intracellularly filled with horseradish peroxidase. We found serotonin axonal contacts on marginal, stalked, and islet cells. Contacts preferentially occurred on dendritic shafts rather than on spines. Marginal and stalked cells received the heaviest innervation.

Animals↗

Extra- and intracellular recordings from dorsal column postsynaptic spinomedullary neurons in the cat.

Dorsal column postsynaptic (DCPS) spinomedullary neurons in the dorsal horn of spinal segments L6-S1 of adult cats anesthetized with sodium pentobarbital were identified by antidromic stimulation of cervical dorsal columns that were dissected free of, and electrically isolated from, the rest of the spinal cord. The neurons were categorized with respect to natural stimulation of their cutaneous receptive fields. An equal number of low-threshold mechanoreceptive and wide-dynamic-range neurons were found. No DCPS neurons could be classified as nociceptive-specific. All neurons received input from low-threshold mechanoreceptors with myelinated axons. There was no evidence that any neurons received monosynaptic input from unmyelinated, primary afferent fibers. The average conduction velocity of the antidromic responses was 45.7 m/s. Nearly half of the DCPS cells showed an antidromic spike followed by synaptically driven responses that were probably evoked by antidromic invasion into the intraspinal collaterals of A-beta primary afferent fibers that ascended the dorsal columns. Intracellularly recorded synaptic responses of DCPS neurons to dorsal column and receptive field stimulation usually consisted of an EPSP with overriding spike potentials followed by a prolonged IPSP whose amplitude decreased markedly as the stimulus frequency was increased in the range of 5 to 30 Hz. The results indicate that DCPS neurons constitute a projection system capable of signaling innocuous and tissue-damaging mechanical stimuli. The DCPS projection may play a role in the modulation of touch and pain perception.

Animals↗

Spinal cord layer I neurons with axon collaterals that generate local arbors.

The morphology an location of physiologically characterized neurons in layer I of the spinal cord dorsal horn were revealed by the intracellular deposition of horseradish peroxidase (HRP). This material showed that the axons of some layer I neurons issue varicosity-bearing collaterals that generate arbors that overlap the neurons' dendritic territories in layer I.

Animals↗