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Biomedical subjects

G H Fromm

Publications and source records attributed to G H Fromm.

At least 19 recordsLinked to original sources
PubMed1994

Baclofen as an adjuvant analgesic.

Baclofen is a gamma-aminobutyric acid (GABA) agonist approved for the treatment of spasticity and commonly used in the management of many types of neuropathic pain. Controlled studies have demonstrated the efficacy of this drug in trigeminal neuralgia. Although its precise mechanism of analgesic action is unknown, it is likely that a drug-induced increase in inhibitory activity is sufficient to interrupt the cascade of neural events that culminates in aberrant activity of wide dynamic range neurons, or more rostral neurons in nociceptive pathways, that is the substrate for some types of neuropathic pain. The optimal use of baclofen as an adjuvant analgesic requires an understanding of its pharmacology, side effect spectrum, and dosing guidelines that have proven useful in clinical practice. Failure of baclofen therapy following a prolonged trial requires dose tapering prior to discontinuation due to the potential for a withdrawal syndrome.

Adjuvants, Pharmaceutic↗
PubMed1994

Gabapentin: discussion.

Gabapentin (GBP, Neurontin) is a novel antiepileptic drug (AED) that was shown to be effective against refractory partial seizures in five placebo-controlled trials. However, a number of patients with complex partial seizures experienced an increase in seizure frequency, suggesting that patients suffering from complex partial seizures are not a homogeneous group. In fact, we found that currently available AEDs are likely to be ineffective when staring is a prominent component of complex partial seizures. The poor response of this group of patients may reflect the fact that staring spells are inhibitory seizures and that the AEDs prescribed for partial seizures appear to facilitate inhibitory mechanisms. GBP resembles phenytoin (PHT) and carbamazepine (CBZ) in depressing segmental and reticular excitatory mechanisms and facilitating segmental inhibitory mechanisms, just as it resembles PHT and CBZ in efficacy against some partial seizures and against secondarily generalized seizures. Perhaps the patients in whom GBP increased seizure frequency had complex partial seizures with staring and were therefore unlikely to benefit from drugs such as GBP, CBZ, and PHT, which enhance inhibitory mechanisms in the brain. These findings suggest that future AED trials would greatly benefit from a categorization of complex partial seizures into nosologically distinct groups.

Acetates↗
PubMed1994

The effect of single-application topical ophthalmic anesthesia in patients with trigeminal neuralgia. A randomized double-blind placebo-controlled trial.

To evaluate the reported benefit of ipsilateral single-application ophthalmic anesthetic eyedrops in patients with typical trigeminal neuralgia, a randomized double-blind placebo-controlled trial was performed. Forty-seven patients were randomly assigned to receive two drops of either proparacaine (25 cases) or saline placebo (22 cases). The experimental and placebo groups were equivalent in regard to patient age, distribution of trigeminal neuralgia pain, duration of pain, current medication regimens, and number of prior procedures performed. Pain response was assessed at 3, 10, and 30 days after instillation using two pain rating scales and a measure of pain frequency. Treatment failure was defined in advance as any of the following: a lack of clinical response, the need for an increase in medication, or the need for surgery. No significant difference in outcomes was found between the two groups either when using a verbal pain rating scale (p = 0.24) or when comparing overall pain status (unchanged, improved throughout the study period, or temporarily improved) (p = 0.98). No difference in the frequency of trigeminal neuralgia attacks between the two treatment groups (scaled within five levels of pain frequency) was detected (p = 0.09). During follow-up monitoring, 11 patients in the test drug group and 14 in the placebo group required surgery because of persistent pain (p = 0.24). The results of this study indicate that single-application topical ophthalmic anesthesia reduces neither the severity nor the frequency of pain in comparison to placebo administration. Although a simple and safe treatment, the single application of topical ophthalmic eyedrops provides no short- or long-term benefit to patients with trigeminal neuralgia.

Administration, Topical↗
PubMed1992

The action of GABAB antagonists in the trigeminal nucleus of the rat.

The iontophoretic administration of the GABAB antagonists (P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid (CGP 35348) and 2-hydroxy-saclofen blocked the action of iontophoretically applied L-baclofen on neurons in the trigeminal nucleus of rats, anesthetized with halothane. The substance CGP 35348 appeared to be more potent than 2-hydroxy-saclofen. The iontophoretic administration of GABA resembled L-baclofen in depressing excitatory transmission and facilitating segmental inhibition in the trigeminal nucleus. The depression of excitatory transmission was also blocked by CGP 35348 and the facilitation of segmental inhibition produced by GABA was partially blocked. These observations indicate that CGP 35348 is not only a baclofen antagonist but actually a GABAB receptor antagonist and the baclofen was acting at GABAB receptors in the trigeminal nucleus. The portion of the effect of GABA, not blocked by CGP 35348, was probably mediated by GABAA receptors, since it was previously found that segmental inhibition in the trigeminal nucleus could be modulated by GABAA agonists and antagonists as well.

Animals↗
PubMed1991

Familial trigeminal neuralgia and Charcot-Marie-Tooth neuropathy. Report of two families and review.

Typical trigeminal neuralgia has occasionally occurred in multiple members of the same family over several generations. The clinical features of such cases, including the increased incidence in females, and the absence of other apparent hereditary, neurologic, metabolic, or structural abnormalities were identical to those of sporadic cases. More rarely, familial trigeminal neuralgia has been described in the setting of hereditary peripheral neuropathy, especially Charcot-Marie-Tooth disease. We describe patients from two different families with Charcot-Marie-Tooth disease and medically intractable trigeminal neuralgia. Both patients were successfully treated by percutaneous retrogasserian glycerol rhizolysis. The occurrence of cranial nerve symptoms in patients with demyelinating peripheral neuropathies is discussed in light of the current hypotheses regarding the etiology of trigeminal neuralgia.

Charcot-Marie-Tooth Disease↗
PubMed1991

Comparison of gabapentin with other antiepileptic and GABAergic drugs.

The effect of the experimental antiepileptic drug gabapentin (1-(aminomethyl) cyclohexane acetic acid; GPT) on the feline trigeminal complex was compared with the effect of established antiepileptic drugs and with the effect of GABAA and GABAB agonists and antagonists. Intravenous injection of 10-60 mg/kg GPT depressed the descending periventricular facilitation of trigeminal nucleus neurons, as well as segmental excitatory mechanisms. On the other hand, GPT usually facilitated, but sometimes depressed, both segmental and periventricular inhibitory mechanisms. GPT thus resembled carbamazepine and phenytoin in its action on excitatory mechanisms and on segmental inhibition, but differed in its effect on inhibitory pathways descending from the reticular formation. In agreement with our observations, GPT has been found to be effective against partial and generalized tonic-clonic seizures, similar to the spectrum of activity of carbamazepine and phenytoin. The action of GPT in our model also resembled that of the GABAB agonist baclofen in its facilitation of reticular and segmental inhibitory mechanisms and its depression of segmental excitatory mechanisms, but differed in its effect on excitatory mechanisms descending from the reticular formation. GPT has also been reported to mimic GABAB receptor activation in other experiments but appeared to act by a GABA-receptor independent mechanism.

Acetates↗
PubMed1991

Why are most GABA agonists not effective antiepileptic drugs?

The role of the GABAergic system in the induction and control of seizures remains elusive despite considerable research. In this report, the action of GABA agonists and antagonists is investigated both iontophoretically and intravenously on the trigeminal nucleus model. This technique permitted us to differentiate the direct effect of these drugs on the trigeminal neurons from the action on neurons elsewhere in the central nervous system which impinge on the trigeminal neurons.

Animals↗
PubMed1991

Differential action of amitriptyline on neurons in the trigeminal nucleus.

We studied the effect of amitriptyline (AMI) on neurons in the spinal trigeminal nucleus caudalis in cats anesthetized with alpha-chloralose. The IV injection of 1.0 to 4.0 mg/kg AMI had a differential effect on the inhibitory mechanisms controlling the responses of these neurons. AMI significantly enhanced the segmental inhibition (SI) of wide dynamic range (WDR) neurons but had little or no effect on low-threshold mechanoceptive neurons. AMI also facilitated the SI of some nociceptive specific (NS) neurons and the periventricular inhibition of some WDR and NS neurons, but these effects were not statistically significant. Our observations suggest that AMI exerts its antineuralgic effect by enhancing the ability of SI to prevent excessive firing of WDR neurons. This supports the notion that neuropathic pain is caused by dysfunction of inhibitory mechanisms in the CNS.

Action Potentials↗
PubMed1990

Effects of D-baclofen and L-baclofen on the trigeminal nucleus.

D-Baclofen reduced the response to L-baclofen in the feline trigeminal nucleus, the spinal cord of the rat and in patients with trigeminal neuralgia, but not in slices of hippocampus or neocortex. The iontophoretic application of 10-20 nA L-baclofen depressed excitatory transmission in the trigeminal nucleus oralis, similar to the effect of 0.1-0.4 mg/kg L-baclofen, given intravenously. The concomitant iontophoresis of 10-20 nA D-baclofen reduced the effect of iontophoretically applied L-baclofen. However, larger doses of D-baclofen (30-60 nA) did not, while still larger doses (200-400 nA) by themselves depressed response of the neuron, similar to the action of small doses of L-baclofen. The iontophoresis of 30-40 nA L-baclofen had a stronger effect than that previously obtained with systemic administration and D-baclofen was not able to block it. These observations suggest that D-baclofen is a partial agonist at the GABAB receptor. Failure to observe a blocking effect of D-baclofen in slices of hippocampus or neocortex could be due to the larger doses used or to a difference in receptor types. The observations emphasise the need to test drugs at therapeutic concentrations in an appropriate model, in order to predict reliably their therapeutic actions.

Animals↗
PubMed1990

Pre-trigeminal neuralgia.

Eighteen patients who subsequently developed typical trigeminal neuralgia experienced a prodromal pain termed "pre-trigeminal neuralgia." These patients described their prodromal pain as a toothache or sinusitis-like pain lasting up to several hours, sometimes triggered by jaw movements or by drinking hot or cold liquids. Typical trigeminal neuralgia developed a few days to 12 years later, and in all cases affected the same division of the trigeminal nerve. Six additional patients experiencing what appeared to be pre-trigeminal neuralgia became pain-free when taking carbamazepine or baclofen. Recognition of pretrigeminal neuralgia makes it possible to relieve the pain with appropriate medications and avoid unnecessary irreversible dental procedures.

Adult↗
PubMed1990

Clinical pharmacology of drugs used to treat head and face pain.

The head and face contain one of the densest and richest nerve supplies in the body. Consequently, the face and head are particularly sensitive to pain, and patients afflicted with pain involving these parts of their bodies often come to feel that they are being subjected to the most unbearable tortures. Fortunately, specific and effective pharmacotherapy is now available for many of these conditions. This article reviews the indications, dosing regimens, and potential side effects of the drugs used for the treatment of trigeminal and glossopharyngeal neuralgia, posttherapeutic neuralgia, temporal arteritis, and migraine based on the clinical pharmacology of these drugs, so that the most appropriate treatment for each patient can be chosen on a sound, rational basis.

Baclofen↗
PubMed1989

Trigeminal neuralgia and related disorders.

Trigeminal neuralgia is probably the most excruciatingly painful disorder to afflict mankind and is refractory to all conventional analgesic agents. Fortunately, a number of specific medical and surgical therapies are now available. An accurate diagnosis is thus essential for the successful management of patients afflicted with trigeminal neuralgia. This article reviews the signs and symptoms, natural history, and diagnosis of trigeminal neuralgia. A discussion follows on current views on its pathogenesis and on available medical and surgical treatment modalities.

Baclofen↗
PubMed1988

Spontaneous remission of paraneoplastic ocular flutter and saccadic intrusions.

We report two women with ocular flutter and saccadic intrusions, documented by electro-oculography, who had complete spontaneous remission of their ocular motor findings prior to the appearance of a primary neoplastic process remote from the nervous system. Transient elevation of blood HVA and VMA levels was detected in one patient who subsequently had breast cancer. These cases indicate that spontaneous remission of saccadic oscillations does not necessarily imply a benign outcome. Patients with this ocular motor abnormality should be followed closely for signs of a remote neoplasm even if initial investigation is negative.

Adult↗
PubMed1987

Differential effect of ethosuximide and of electrical stimulation on inhibitory and excitatory mechanisms.

Much longer trains of conditioning stimuli are required to elicit inhibition descending from the reticular formation than to elicit segmental inhibition in the trigeminal nucleus. In contrast, a single conditioning stimulus is the most effective in eliciting descending facilitation, while the test stimulus alone is most effective in eliciting segmental excitation. Ethosuximide (ESM) selectively depresses descending inhibition and to a lesser extent segmental inhibition. Thus, ESM only depresses pathways requiring repetitive stimulation, such as inhibitory pathways in the reticular formation. This action would account for ESM's specificity for absence seizures, which are probably due to paroxysmal activity in inhibitory pathways.

Animals↗