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Allodynia is a well-known component of neuropathic pain resulting from injury to the nervous system. Clinical pain states with allodynia in connection with longstanding superficial wounds have, however, not been reported in the literature. In this case a chronic pain state developed in a previously healthy 17-year-old girl in and around a persistently suppurating appendectomy wound. There was no...
The effect of continuous subcutaneous (s.c.) infusion of ketamine on nerve injury pain was examined in patients with post-herpetic neuralgia. Five patients that reported pain relief after acute intravenous injection of ketamine were included in this open prospective study. Ketamine was administered continuously in increasing doses using a portable infusion pump (CADD-PLUS, Pharmacia), and the treatment...
We examined the analgesic effect of racemic ketamine and its 2 enantiomers in 16 female patients (age: 20-29 years) suffering acute pain after oral surgery and in 7 female patients (age: 42-79 years) suffering chronic neuropathic orofacial pain. All 3 forms of ketamine consistently relieved postoperative pain, (S)-ketamine being 4 times more potent than (R)-ketamine. The analgesic effect was maximal...
A double-blind multidose trial of the addition of ketamine (0-40 mg, i.m., 8 times per day) to intramuscular morphine therapy was undertaken in a 61-year-old man with chronic back pain related to osteoporosis who had received inadequate pain relief from anterior interbody fusion, dorsal column stimulation and morphine alone. The patient reported only mild side effects. Nausea, tiredness and well-being...
The importance of N-methyl-d-aspartate (NMDA) receptor-mediated sensitization of central nervous system (CNS) neurons is well established in animal models of acute and chronic pain. A human model of central sensitization would be useful in screening new NMDA antagonists and establishing dose regimens for clinical trials in patients with pain related to sensitization Of CNS neurons. We used this model...
The importance of N-methyl-d-aspartate (NMDA) receptor-mediated sensitization of central nervous system (CNS) neurons is well established in animal models of acute and chronic pain. A human model of central sensitization would be useful in screening new NMDA antagonists and establishing dose regimens for clinical trials in patients with pain related to sensitization Of CNS neurons. We used this model...
Ten patients (4 female, 6 male) aged 34-67 years suffering from peripheral neuropathic pain participated in a double-blind placebo-controlled study where ketamine or magnesium chloride were administered by a 10 min bolus infusion (ketamine: 0.84 μmol/kg = 0.2 mg/kg, magnesium: 0.16 mmol/kg) followed by a continuous infusion (ketamine: 1.3 μmol/kg/h = 0.3 mg/kg/h, magnesium: 0.16 mmol/kg/h). Ongoing...
The non-competitive NMDA-antagonist, Ketamine, was infused (i.v.) in healthy volunteers to study the effect on central excitability with the presence of cutaneous hyperalgesia. Hyperalgesia was established experimentally on the dorsum of the foot by topical application of capsaicin (1%). Different thermal and mechanical conditioning stimuli were applied to the primary and secondary hyperalgesic areas...
Hyperactivity of N-methyl d-aspartate (NMDA) receptors may be one of the factors in the maintenance of persistent stump and phantom limb pain. Ketamine (bolus at 0.1 mg/kg/5 min followed by an infusion of 7 μg/kg/min) was administered intravenously to 11 patients with established stump and phantom limb pain in a double-blind saline-controlled study. All 11 patients responded with a decrease in the...
In an attempt to clarify the neurochemical background of central post-stroke pain and to undertake a pharmacological analysis, the basic pharmacological characteristics of this intractable pain syndrome were investigated by the morphine, thiamylal and ketamine tests. In addition, the correlation between the pharmacological characteristics and the effects of chronic motor cortex stimulation therapy...
Effects of morphine and ketamine (NMDA receptor antagonist) on temporally summated pain (`wind-up-like pain') and spatial aspects of secondary hyperalgesia were investigated in 12 healthy volunteers. Hyperalgesia was produced by a local 1° burn injury covering 12.5 cm 2 on the medial surface of the calf. Primary hyperalgesia was determined by measuring heat pain detection threshold (HPDT)...
Recent evidence suggests that central pain, i.e., pain due to central nervous system damage, may be due to a deranged neurotransmission between the sensory thalamus and sensory cortical areas. Central pain can be controlled either by opposing glutamate neurotransmission or potentiating GABAergic transmission. It is speculated that a relative hypofunction of the GABAergic inhibition both at thalamic...
The compatibility of ketamine and morphine mixture was studied. In addition, pH adjustment to minimise local tissue irritation led to no change in stability of the mixture up to pH 5.9. It appears that ketamine and morphine mixtures are stable over a 24 h period.
A 14-year-old male patient developed severe right limb pain after traumatic sciatic nerve injury. His pain was diagnosed as neuropathic pain (complex regional pain syndrome, type II). He did not respond to any conventional therapy for limb pain including non-steroidal anti-inflammatory drugs, antidepressants, anticonvulsants, continuous epidural administration of local anesthetics and psychotherapy...
N-methyl-d-aspartate (NMDA) receptors appear to play little part in nociceptive responses evoked by acute stimulation of normal somatic tissues, but rather are involved in hyperalgesic responses after peripheral injury and inflammation. Previous studies from this laboratory have shown important differences in the neural organization of somatic and visceral nociceptive pathways. Here, we have explored...
The present study was designed to evaluate the oral efficacy and bioavailability of ketamine. Antinociceptive efficacy was determined with the rat formalin test and oral bioavailability by the measurement of plasma and brain concentrations of ketamine and its major metabolite, norketamine. Oral ketamine in a dose range from 30 to 180 mg/kg or saline was given prior to intraplantar formalin and the...
Ketamine hydrochloride is a well known general anesthetic and short acting analgesic in use for almost 3 decades. The role of the NMDA receptor in the processing of nociceptive input has led naturally to renewed clinical interest in N-methyl-d-aspartate (NMDA) receptor antagonists such as ketamine. This paper reviews the use and efficacy of low-dose ketamine in the management of acute postoperative...
The NMDA receptor has been reported to be involved in opioid tolerance. Adjuvant subcutaneous infusion treatment with (very) low-dose ketamine, a NMDA receptor antagonist, improves analgesia and at the same time appears to reduce morphine tolerance. Three cases are presented.
We examine the effect of morphine or ketamine (N-methyl-d-aspartate receptor antagonist; NMDA) treatment on secondary hyperalgesia. Drug treatment started preinjury and continued into the early postinjury period. Hyperalgesia was induced by a local 1 o burn injury covering 12.5 cm 2 on the medial side of the calf. In this double-blind, cross-over study, 12 healthy volunteers received,...
Both μ opioid agonists and N-methyl-d-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a μ-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine...
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