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Biomedical subjects

F Svendsen

Publications and source records attributed to F Svendsen.

At least 19 recordsLinked to original sources

[Future pain treatment].

BACKGROUND: The recent rapid progress in pain research is due in large part to advances in genetics and cell and molecular biology. We now know that chronic pain (hypersensitivity due to inflammation or nerve injury) and acute nociceptive pain are different and must be treated accordingly. We will continue to reveal sophisticated mechanisms underlying different kinds of pain that can be targeted to inhibit nociceptive transmission and produce analgesia. METHODS: This review is based upon literature collected through the authors' own reading and through PubMed searches. New hopes for future pain treatments are discussed. Further, the impact of genetic factors on pain sensitivity and pain modulation are discussed, and conceivable therapeutic approaches based on genetic techniques are mentioned. RESULT: At the level of the peripheral nerve, many novel targets have recently been identified: the tetrodotoxin-resistant sodium channel, the vanilloid receptor and different calcium channels are very interesting. In the spinal cord, different approaches can be used: to either block excitatory input or to increase inhibitory control or to do both at the same time. The mechanisms for hypersensitivity are being identified and offer multiple possible targets for novel analgesics. INTERPRETATION: Many interesting targets for analgetics has emerged during that last few years, lending great hope for new and better (i.e. with less side effects) analgesic drugs in the future.

Analgesia↗

[Surgical treatment of normal pressure hydrocephalus].

Normal pressure hydrocephalus (NPH) is an important diagnosis to keep in mind, i.e. the possibility that NPH and not a neurodegenerative disease causes the patient's symptoms with ataxia, urinary incontinence and dementia. Clinical improvement, sometimes a complete reversal of the symptoms, may be seen after a simple surgical procedure. This prospective study was performed by testing eight consecutively shunted patients with a walking test and a cognitive test battery pre- and postoperatively. Improvement 3-4 months after the shunting procedure suggests that NPH was present in six of eight patients. Walking ability was improved after surgery, also in patients with severe dementia. Severe dementia caused by NPH is hardly reversible, though cognitive tests may indicate some improvement. However, early surgical treatment of NPH in patients not suffering from a dementia according to the Mini Mental Status Test may bring improvement in some cognitive functions. Patients with both clinical and radiological signs of normal pressure hydrocephalus should be offered a shunting procedure.

Aged↗

Randomized study of coagulation and fibrinolysis during and after gasless and conventional laparoscopic cholecystectomy.

BACKGROUND: Carbon dioxide pneumoperitoneum may be an important pathophysiological factor stimulating the coagulation system during conventional laparoscopic cholecystectomy. The aim of this study was to test the hypothesis that gasless laparoscopy produces smaller changes in the coagulation and fibrinolytic system than carbon dioxide pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. METHODS: Fifty patients were allocated randomly to conventional (n = 26) or gasless (n = 24) laparoscopic cholecystectomy. Blood samples were obtained on admission, after induction of anaesthesia, after insufflation or traction, 30 min after introduction of the laparoscope, 10 min after exsufflation of carbon dioxide or traction, 4 h after extubation and 24 h after operation. RESULTS: The two groups were comparable with respect to age, sex, body mass index and duration of operation. Plasma levels of prothrombin fragment 1 and 2 (F1 + 2), soluble fibrin and D-dimer did not differ between the two groups. F1 + 2 levels varied significantly in both groups during and after operation (P < 0.001). Soluble fibrin and D-dimer levels did not change during operation in either group, but after operation the levels increased significantly in both groups (P < 0.001). CONCLUSION: Carbon dioxide pneumoperitoneum does not enhance the activation of coagulation and fibrinolysis associated with laparoscopic cholecystectomy. The coagulation and fibrinolytic systems are activated during and after gasless as well as conventional laparoscopic cholecystectomy.

Adult↗

Inhibition of spinal nociceptive responses after intramuscular injection of capsaicin involves activation of noradrenergic and opioid systems.

Extracellular recordings of wide dynamic range neurones in the dorsal horn driven by electrical stimulation of the sciatic nerve were performed in intact urethane-anaesthetized Sprague-Dawley rats. The electrically evoked neuronal responses were defined as A- and C-fibres responses according to latencies, and the effect of a deep nociceptive conditioning stimulus induced by 200 microg capsaicin (8-methyl-N-vanillyl-6-noneamide) injected into the contralateral gastrocnemius-soleus muscle was studied for at least 30 min. Independent of the size and location of the receptive field of the neurone under study, a clear inhibition of the neuronal responses was observed. The electrically evoked C-fibre responses were inhibited to 53% of baseline 15-30 min after injection of capsaicin. This inhibition was only slightly attenuated by 125 nmol of the alpha-adrenoceptor antagonist phentolamine or 250 nmol of the opioid receptor antagonist naloxone applied directly onto the spinal cord when the two compounds were administered separately 5 min before capsaicin. In contrast, when a mixture of the two compounds was given 5 min before capsaicin, the effect of capsaicin was completely abolished. These results indicate that activation of the capsaicin-sensitive afferents in the gastrocnemius-soleus muscle inhibits the electrically evoked C-fibre responses in the dorsal horn by activating noradrenergic and opioidergic inhibitory systems. Moreover, our data indicate that the activation of these two systems following injection of capsaicin has a sub-additive inhibitory effect on the wide dynamic range neurones in the spinal cord. We conclude that only one of these systems is sufficient for the inhibition to occur.

Adrenergic alpha-Antagonists↗

[Intracranial arachnoidal cysts--localization, gender and sidedness].

The aim of the present study was to investigate whether data on location and distribution of intracranial cysts in a large patient population may explain why and how such cysts are formed. We investigated 123 patients with 129 intracranial cysts, consecutively admitted to the Department of Neurosurgery in Bergen 1988-97. Data were analyzed with regard to intracranial location and gender distribution. Cysts were much more commonly located in the temporal fossae than one would expect if the distribution were random; 68.1% of patients had temporal cysts. We suggest a theory that may explain how mal-development of the leptomeninges may contribute to the formation of cysts, and why such cysts are more common in the temporal fossae. Temporal cysts were significantly more frequent in males than in females (3.9:1), while cysts of other locations did not show preponderance for a specific gender. New in this study is the interesting connection between gender distribution and sidedness: the significant predominance of left-sided temporal cysts was found only in males. In patients with a unilateral temporal cyst, the left/right ratio was 2.0:1 (males 44 left and 20 right, females eight left and six right). We discuss whether the preponderance of left-sided temporal cysts in males can be explained by a gender specific developmental failure, as previously suggested for dyslexia.

Adolescent↗

Long term potentiation of single WDR neurons in spinalized rats.

We report long-term potentiation (LTP) in single spinal wide dynamic range (WDR) neurons in urethane-anaesthetized spinalized rats with a complete neuromuscular blockade. Peripheral influences were excluded by a complete lidocaine block distal to the stimulation site on the sciatic nerve. As previously shown A-beta fibre evoked responses were not increased by the tetanic stimulation when there was a neuromuscular blockade during the experiment. Spinalization, excluding influences from supraspinal structures, increased all firing responses, and the LTP of C-fibre evoked responses when calculated in number of action potentials compared to intact animals and to previous studies. Furthermore, an LTP of the post discharge was observed after spinalization. An LTP of the post discharge has previously not been reported. Therefore, we conclude that LTP in the dorsal horn normally seems to be inhibited by descending pathways.

Analysis of Variance↗

Expression of long-term potentiation in single wide dynamic range neurons in the rat is sensitive to blockade of glutamate receptors.

Plasticity in pain control systems may play an important role in clinical pain and some mechanisms of plasticity may be similar to those involved in learning. In this study we investigate the importance of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors for the maintenance of long-term potentiation (LTP) in wide dynamic range (WDR) neurons. Doses of 6-nitro-7-sulphomoylbenzoylquinoxaline-2,3-dione disodium (NBQX) and D-Q-amino-5-phosphonopentanoic acid (D-AP5) equipotent in reducing C-fiber mediated responses in controls, reduced the established LTP by about 50 and 80%, respectively. The drug effect lasted less than 1 h in controls. After induction of LTP, NBQX caused a reversible reduction of the potentiation. D-AP5, however, caused a stronger attenuation of the LTP, outlasting the effect of the drug in controls. We suggest that both pre-emptive analgesia preventing LTP induction and an early reduction of the excitation of neurons is important for the inhibition of LTP and central sensitization. Thus, it is possible that an early antinociceptive treatment preventing an excessive excitation of neurons in the dorsal horn may be of importance in preventing longlasting and pathological pain states.

2-Amino-5-phosphonovalerate↗

Inhibition of evoked C-fibre responses in the dorsal horn after contralateral intramuscular injection of capsaicin involves activation of descending pathways.

In this study extracellular recordings of nociceptive dorsal horn neurones driven by electrical stimulation of the sciatic nerve were performed in intact urethane-anaesthetized Sprague-Dawley rats. Spikes 0-40, 40-250 and 250-800 ms after stimulus were defined as A- and C-fibre responses and post-discharge, respectively, and the effect of 200 microg capsaicin (8-methyl-N-vanillyl-6-noneamide) injected into the contralateral gastrocnemius-soleus muscle was investigated. In most cells tested, regardless of the size or location of their receptive fields, the injection of capsaicin caused a clear inhibition of the electrically evoked C-fibre responses. In animals with intact descending pathways the mean C-fibre response was inhibited to 51% of baseline 15 min after injection of capsaicin. In contrast, when capsaicin was given during cold block of the spinal cord between the brainstem and the site of recording in the dorsal horn, the same response was inhibited to 91% of baseline. A significant interaction between cold block and capsaicin was detected. We conclude that stimulation of capsaicin-sensitive afferents in the deep tissue in the hind limb can inhibit the electrically evoked C-fibre responses in the dorsal horn by activating inhibitory descending projections from higher centres. The model presented here may be an important tool for further investigations of the endogenous descending antinociceptive system.

Action Potentials↗

Recording of long-term potentiation in single dorsal horn neurons in vivo in the rat.

We have published several reports on long-term potentiation (LTP) in single spinal wide dynamic range (WDR) neurons (responding to both innocuous and noxious stimuli) in urethane-anaesthetised rats. The protocol presented here, with single unit recordings of dorsal horn neurons before and after a nociceptive conditioning stimulation, may be useful in many electrophysiological studies of plastic changes in the spinal cord, such as LTP. We invite others to use this protocol for the study of spinal plasticity. Findings using this technique may be relevant for the understanding of changes in nociceptive transmission, induction of central sensitisation and maybe even in mechanisms of pathological pain and chronic pain states. We describe modified and alternative protocols for the study of LTP mechanisms under different conditions in intact and in spinalised animals, and after natural noxious stimuli. We present a novel method minimising peripheral influence of afferent input induced by antidromic neurogenic inflammation or inflammatory changes following a natural noxious stimulation. This is made possible by dissection of the sciatic nerve at two separate locations and local anaesthetic block distal to the stimulation site.

Anesthetics, Local↗

Behavioural effects of LTP-inducing sciatic nerve stimulation in the rat.

A short-lasting tetanic sciatic nerve stimulation that previously has been shown to be nociceptive only during the stimulation, induces long-term potentiation (LTP) of nociceptive evoked responses in wide dynamic range neurons in the dorsal horn of rats. The LTP may contribute to the process of central sensitization. We have shown that the tetanic conditioning stimulation with muscular contractions induces LTP of both Abeta- and C-fibre evoked responses. However, the same stimulation during muscular paralysis induces LTP only of C-fibre evoked responses. In the present study, we investigated the effects of this conditioning stimulation with or without muscular paralysis in behavioural tests in rats. Conditioning stimulation with muscular contractions caused a significant reduction of weight borne on the stimulated side, suggesting muscular soreness and peripheral sensitization. Conditioning stimulation during neuromuscular paralysis, which only has given LTP of C-fibre evoked responses in intact animals, caused no change in the weight borne on the stimulated side, suggesting less or even absence of allodynia. However, in these animals the response temperature in the hot plate test was increased both on the stimulated and on the contralateral side compared to sham-operated rats. In view of our recent results indicating that a descending inhibition reduces the expression of LTP in dorsal horn cells, and the suggestion by others that long-term descending inhibition may override a segmental facilitation, it is suggested that an increased long-lasting endogenous nociceptive inhibition is induced after LTP-inducing stimulation. This is an interesting parallel to stimulation-induced analgesia in humans. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

AMPA and NMDA receptor-dependent spinal LTP after nociceptive tetanic stimulation.

LTP is often studied as a model of synaptic plasticity. Plasticity in pain control systems may involve mechanisms similar to those involved in learning. We recently reported LTP of both the A beta and C-fibre evoked responses of single dorsal horn neurons after a tetanic stimulation of the sciatic nerve, lasting for at least 6 h. In the present paper we show that identical stimulation induced LTP only of the C-fibre evoked response after blockade of muscular contractions during the tetanus. The C-fibre evoked response increased significantly less after pretreatment with either the AMPA antagonist NBQX or the NMDA antagonist D-AP5 (mean increase 33%) than in untreated animals (105%, p < 0.001), indicating that both AMPA and NMDA receptor stimulation are involved in the induction of LTP.

2-Amino-5-phosphonovalerate↗

LTP of spinal A beta and C-fibre evoked responses after electrical sciatic nerve stimulation.

Plasticity in the central nervous system may play an important role in clinical pain. The present study shows that long-term potentiation (LTP) may be induced in single wide dynamic range (WDR) neurons in the dorsal horn after high-frequency stimulation of the sciatic nerve in intact urethane anaesthetized rats. Extracellular recordings of firing responses after single pulse stimuli were made. The high-frequency conditioning stimulus increased the A beta- and C-fibre-mediated firing responses to single pulse stimuli by 60 and 130%, respectively, for more than 6 h. This finding supports a role for WDR neurons in 'nociceptive memory' in the dorsal horn. The model presented here may be an important tool for further investigations of mechanisms of plasticity within the dorsal horn.

Afferent Pathways↗

Reliability of skin prick tests during terfenadine treatment in adults with pollen rhinitis. A clinical study.

The variation in skin prick test (SPT) results was evaluated clinically during terfenadine treatment in 39 adult patients with pollen rhinitis. A change in the perceived state of the patient as regards sensitization to a specific pollen allergen or atopic constitution was judged to be clinically important. A randomized, double-blind, crossover design was used, comprising 2 weeks on terfenadine 120 mg once a day and 2 weeks on placebo. SPT for two pollen allergens and histamine (10 mg/ml) were evaluated at the start of the study and at the end of each period. When SPT was used as a discovery test and liberal definitions were applied, predictive values for a positive test were 100%. 1-Sensitivity ranged between 10 and 54% with substantially lower values when a histamine wheal reaction was noted. The inhibitory effect of terfenadine was detectable 2 weeks after withdrawal as a reduction in the median of the mean diameter for the histamine-induced wheal response of 1 mm (0-1.5). The data implied that a positive SPT is reliable when liberal definitions are adopted for sensitization and atopy; a negative SPT is presumably reliable when the measurement artifact is considered and the wheal reaction to histamine is detectable.

Adolescent↗

Shunt failures and complications in adults as related to shunt type, diagnosis, and the experience of the surgeon.

Data from 95 adult patients (43 males, 52 females) treated with ventriculoperitoneal shunts during an 8-year period were analyzed to investigate risk factors in shunt surgery. All patients were seen in the authors' department and were grouped according to the cause or type of hydrocephalus. The operating surgeons were divided into two categories: specialists and residents. The shunts were classified as single- (Orbis-Sigma) or multicomponent (Holter or Hakim) systems. Two types of unfavorable events were recognized: complications and shunt malfunction. A total of 143 surgical procedures (implantations and revisions) were performed in the 95 patients; 24 patients had their shunts revised, and there were 13 complications (one fatal, five severe) resulting from the shunt surgery. The following observations were statistically significant: 1) patients with normal pressure hydrocephalus had no complications from shunt surgery; 2) the number of shunt malfunctions was lower in patients with intracranial hemorrhages than in the other groups; 3) residents performed a higher number of inadequate operations than did specialists; and 4) the infection rate was higher among patients operated on by residents. The choice of shunt type, the perioperative use of antibiotics, and the degree of surgical emergency were not correlated with complication or failure rates.

Adolescent↗

Popliteal arterial aneurysm.

Popliteal arterial aneurysms are rare in young individuals. A case without a penetrating trauma presenting in a young woman is described. Complications may lead to vascular emergencies. Early diagnosis and surgical treatment is important.

Adolescent↗