The therapeutic effects of dextrorphan and ketamine, two non-competitive N-methyl-D-aspartate (NM... more The therapeutic effects of dextrorphan and ketamine, two non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, on neuropathic pain-related behaviors were examined in rats with peripheral mononeuropathy induced by loose ligation of the common sciatic nerve (chronic constrictive injury, CCI). Four daily intrathecal treatments (beginning 1 h after nerve ligation) with dextrorphan or ketamine (12.5-100 nmol) reliably attenuated hyperalgesia to radiant heat and spontaneous pain-related behaviors in CCI rats. Thermal hyperalgesia also was reduced in CCI rats receiving a single intrathecal treatment with either dextrorphan or ketamine (50 and 100 nmol for each compound) on day 3 after nerve ligation when thermal hyperalgesia was well developed. Since both dextrorphan and ketamine are currently utilized in other clinical applications, the results suggest a new therapeutic utility of these 'old' compounds in treatment of neuropathic pain syndromes resulting from peripheral nerve injury.
Forty male veterans who had been injured during their military service in the Israeli Defense For... more Forty male veterans who had been injured during their military service in the Israeli Defense Forces were assessed for pain threshold and tolerance in a thermal pain procedure. Based on their medical records, subjects were classified by three independent judges as having been either severely or lightly injured. Veterans who had been severely injured had much higher threshold and tolerance for thermal pain as compared to lightly injured veterans. These results are interpreted as supporting adaptation-level theory, which implies that painful experiences can change the internal anchor points for the subjective evaluation of pain.
Early studies suggested that newborn animals are far more susceptible to the convulsant effect of... more Early studies suggested that newborn animals are far more susceptible to the convulsant effect of systemic morphine than adult animals. The present study reassessed morphine's (0, 6, 12.5, 25, 50, 100 and 300 mg/kg) toxic effects, making use of electroencephalographic (EEG) recordings, behavioral observations and the specific opiate antagonist naloxone in immature rats (postnatal days 1, 3, 6, 12 and 24). Although morphine had opiate-specific effects (such as inhibition of activity at low doses), non-specific effects (such as hyperactivity) elicited by the highest doses, predominated in the 3 youngest age groups. At day 12 high doses of morphine first produced Straub tail and catatonia. At this age morphine produced EEG spikes that were not reversed by naloxone. Only at day 24 were electrographic spikes temporarily inhibited by naloxone. Behavioral convulsions were never observed, at any age. These findings indicate that morphine is less toxic in newborns than suggested previously.
Surgical procedures using hypothermic temperatures have been linked to complications such as seiz... more Surgical procedures using hypothermic temperatures have been linked to complications such as seizures, impaired mental development and impaired memory. Although there is some evidence that the profound hypothermia (<12 ( composite function)C) used in these procedures may be contributing to these neurological impairments, skepticism remains because of lack of evidence from experimental studies isolating the effects of hypothermia on neuronal networks. In order to attain a better understanding of profound hypothermia effects on neurons during surgical procedures, we applied cold to a cultured in-vitro neuronal network. The typical pattern of activity of such cultures is in the form of synchronized bursts, in which most of the recorded neurons fire action potentials in a short time period. In most cases, the bursting activity shows one or more repeating precise spatio-temporal patterns (motifs) that are sustained over long periods of time. In this experimental study, neuronal networks grown on microelectrode arrays (MEA) are subjected to profound hypothermia for an hour and the collective dynamics of the network as a whole are assessed. We show, by using a similarity analysis that compares changes in the time delays between neuronal activation at different burst motifs, that neuronal networks survive total inhibition by profound hypothermia and retain their intrinsic synchronized burst motifs even with substantial generalized neuronal degeneration. By applying multiple sessions of cold, we also show a marked monotonic reduction in the rate of burst firing and in the number of spikes of each neuron after each session.
Nicotine is almost universally believed to be the major factor that motivates smoking and impedes... more Nicotine is almost universally believed to be the major factor that motivates smoking and impedes cessation. Authorities such as the Surgeon General of the USA and the Royal College of Physicians in the UK have declared that nicotine is as addictive as heroin and cocaine. This book is a critique of the nicotine addiction hypothesis, based on a critical review of the research literature that purports to prove that nicotine is as addictive drug. The review is based on a re-examination of more than 700 articles and books on this subject, ...
The therapeutic effects of dextrorphan and ketamine, two non-competitive N-methyl-D-aspartate (NM... more The therapeutic effects of dextrorphan and ketamine, two non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, on neuropathic pain-related behaviors were examined in rats with peripheral mononeuropathy induced by loose ligation of the common sciatic nerve (chronic constrictive injury, CCI). Four daily intrathecal treatments (beginning 1 h after nerve ligation) with dextrorphan or ketamine (12.5-100 nmol) reliably attenuated hyperalgesia to radiant heat and spontaneous pain-related behaviors in CCI rats. Thermal hyperalgesia also was reduced in CCI rats receiving a single intrathecal treatment with either dextrorphan or ketamine (50 and 100 nmol for each compound) on day 3 after nerve ligation when thermal hyperalgesia was well developed. Since both dextrorphan and ketamine are currently utilized in other clinical applications, the results suggest a new therapeutic utility of these 'old' compounds in treatment of neuropathic pain syndromes resulting from peripheral nerve injury.
Forty male veterans who had been injured during their military service in the Israeli Defense For... more Forty male veterans who had been injured during their military service in the Israeli Defense Forces were assessed for pain threshold and tolerance in a thermal pain procedure. Based on their medical records, subjects were classified by three independent judges as having been either severely or lightly injured. Veterans who had been severely injured had much higher threshold and tolerance for thermal pain as compared to lightly injured veterans. These results are interpreted as supporting adaptation-level theory, which implies that painful experiences can change the internal anchor points for the subjective evaluation of pain.
Early studies suggested that newborn animals are far more susceptible to the convulsant effect of... more Early studies suggested that newborn animals are far more susceptible to the convulsant effect of systemic morphine than adult animals. The present study reassessed morphine's (0, 6, 12.5, 25, 50, 100 and 300 mg/kg) toxic effects, making use of electroencephalographic (EEG) recordings, behavioral observations and the specific opiate antagonist naloxone in immature rats (postnatal days 1, 3, 6, 12 and 24). Although morphine had opiate-specific effects (such as inhibition of activity at low doses), non-specific effects (such as hyperactivity) elicited by the highest doses, predominated in the 3 youngest age groups. At day 12 high doses of morphine first produced Straub tail and catatonia. At this age morphine produced EEG spikes that were not reversed by naloxone. Only at day 24 were electrographic spikes temporarily inhibited by naloxone. Behavioral convulsions were never observed, at any age. These findings indicate that morphine is less toxic in newborns than suggested previously.
Surgical procedures using hypothermic temperatures have been linked to complications such as seiz... more Surgical procedures using hypothermic temperatures have been linked to complications such as seizures, impaired mental development and impaired memory. Although there is some evidence that the profound hypothermia (<12 ( composite function)C) used in these procedures may be contributing to these neurological impairments, skepticism remains because of lack of evidence from experimental studies isolating the effects of hypothermia on neuronal networks. In order to attain a better understanding of profound hypothermia effects on neurons during surgical procedures, we applied cold to a cultured in-vitro neuronal network. The typical pattern of activity of such cultures is in the form of synchronized bursts, in which most of the recorded neurons fire action potentials in a short time period. In most cases, the bursting activity shows one or more repeating precise spatio-temporal patterns (motifs) that are sustained over long periods of time. In this experimental study, neuronal networks grown on microelectrode arrays (MEA) are subjected to profound hypothermia for an hour and the collective dynamics of the network as a whole are assessed. We show, by using a similarity analysis that compares changes in the time delays between neuronal activation at different burst motifs, that neuronal networks survive total inhibition by profound hypothermia and retain their intrinsic synchronized burst motifs even with substantial generalized neuronal degeneration. By applying multiple sessions of cold, we also show a marked monotonic reduction in the rate of burst firing and in the number of spikes of each neuron after each session.
Nicotine is almost universally believed to be the major factor that motivates smoking and impedes... more Nicotine is almost universally believed to be the major factor that motivates smoking and impedes cessation. Authorities such as the Surgeon General of the USA and the Royal College of Physicians in the UK have declared that nicotine is as addictive as heroin and cocaine. This book is a critique of the nicotine addiction hypothesis, based on a critical review of the research literature that purports to prove that nicotine is as addictive drug. The review is based on a re-examination of more than 700 articles and books on this subject, ...
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