[Cancer in children--good results can be even better].
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Child↗
Biomedical subjects
Frode Svendsen
Publications and source records attributed to Frode Svendsen.
Long-term potentiation in spinal nociceptive systems--how acute pain may become chronic.
Chronic pain is a major problem since it is difficult to treat and the understanding of the underlying neurobiology is sparse. The mechanisms underpinning the transition of acute into chronic pain remain unclear. However, long-term potentiation (LTP) in spinal nociceptive systems may be one such mechanism. Here, we briefly review the literature regarding LTP in spinal nociceptive systems including our own data on LTP in deep convergent nociceptive neurons. Furthermore, we discuss the role of this phenomenon in understanding the neurobiology of chronic pain and the possible therapeutic implications.
Acute Disease↗
[Spasticity treated with selective posterior rhizotomy].
BACKGROUND: Spasticity is often seen in patients with central nervous lesions. Some patients with severe spasticity are not optimally treated with physiotherapy and medication. MATERIAL AND METHODS: We present a case history of a 41-year-old woman with multiple sclerosis and severe painful spasticity in her lower limbs. Her spasticity did not respond to treatment with physiotherapy, spasmolytic medication, botulinum toxin A, intrathecal baclofen or epidural spinal cord stimulation. RESULT: The patient was treated with selective posterior rhizotomy S1-L1. Section of 60% of the rootlets on the right side and 40% on left the side resulted in a good outcome with less spasticity and pain. Finally her contractures were treated with tenotomy and myotomy, also with good functional result. INTERPRETATION: Patients suffering from severe painful spasticity and who do not respond to physiotherapy in combination with other spasmolytic medication should be considered for surgical treatment. In some patients posterior rhizotomy is the treatment of choice.
Adult↗
Cellular memory in spinal nociceptive circuitry.
Besides transmitting and processing, neurons may also store information for prolonged periods of time (e.g. by use-dependent change in synaptic strength). In 1966 long-term potentiation (LTP) of synaptic transmission was discovered in the hippocampus, an area implicated in learning and memory. Recent studies show that similar mechanisms apply to pain pathways, at least in the spinal cord, and may account for some forms of clinical problems like hyperalgesia, allodynia, and deafferentation pain states, such as phantom pain. In this review, we briefly summarize key aspects of synaptic plasticity known from the brain and in the spinal cord. Then we describe and discuss related changes in spinal nociceptive neurons based on results from our own laboratory.
Humans↗
Increased spinal N-methyl-D-aspartate receptor function after 20 h of carrageenan-induced inflammation.
Spinal N-methyl-D-aspartate (NMDA) receptors are thought to be important in states of central hyperexcitability induced by e.g. inflammation or painful neuropathies. The carrageenan model of inflammatory pain has been and still is widely used as is the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5) to investigate NMDA receptor function. Here we present two novel findings using electrophysiological technique: the NMDA receptor function in the spinal cord is increased following 20 h of carrageenan-induced inflammation and further that only the D-isomer of AP5 is active in the spinal cord. Exogenous NMDA (0.5 and 5 nmol) applied onto the dorsal spinal cord produced a significantly greater facilitation and D-AP5 (1.25 micromol) a significantly greater inhibition of the C-fibre evoked response of the wide dynamic range (WDR) neurones studied in carrageenan (20 h after injection) compared to control rats. The present and two recent studies suggest central changes are different and possibly greater in the later (20 h) compared to the earlier (2-6 h) phase of carrageenan-induced inflammation. In conclusion, 20 h of carrageenan-induced inflammation increases the function of spinal NMDA receptor involved in nociceptive transmission and in addition the D-isomer of AP5 should be used when NMDA receptor antagonism is wanted in the spinal cord.
2-Amino-5-phosphonovalerate↗
Natural noxious stimulation can induce long-term increase of spinal nociceptive responses.
It is conceivable that plasticity in pain control systems and chronic pain may be due to mechanisms similar to learning. Long-term potentiation (LTP) in the hippocampus is often studied as a model of learning and memory. It has recently been shown that long-term excitation may be induced in single wide dynamic range (WDR) neurones in the spinal dorsal horn of rats after tetanic stimulation to the sciatic nerve. The present study shows that similar long-term changes can also be induced by a severe natural stimulus. Single unit extracellular recordings were made in urethane anaesthetized rats and the firing responses of WDR neurones evoked by a single electrical stimulus to the peripheral nerve were recorded every 4 min. After repeated crushing of tissue (including bone) corresponding to the receptive field of the WDR neurones (the conditioning stimulus) followed by a proximal total peripheral nerve block, the C-fibre evoked responses were increased (P < 0.001) for a 3 h observation period compared with baseline responses and control animals. In control animals the nerve block was applied before the conditioning stimulus. We suggest that a long-term increase of the excitability of WDR neurones may be important for the development of long lasting and chronic pain disorders after an acute but severe noxious stimulus.
Analysis of Variance↗
Dorsal horn NMDA receptor function is changed after peripheral inflammation.
The N-methyl-D-aspartic acid (NMDA) receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP5) caused a stronger inhibition of wind-up in single wide dynamic range (WDR) neurons after carrageenan inflammation compared with control neurons without inflammation in the receptive field. This indicates that even a short period (2.5 h) of inflammation induces changes in the function of NMDA receptors. The drug effect was also studied in separate control experiments with few wind-up inducing stimulus trains and little nociceptive input prior to baseline recordings. In these control experiments all evoked responses were reduced by the drug, but the wind-up was significantly increased. A wind-up increase after NMDA receptor antagonism has been reported in two previous studies. Thus, other mechanisms than NMDA receptor stimulation may be more important for the wind-up in not sensitized dorsal horn neurons. As for long-term potentiation, it seems that NMDA receptor antagonists have an increased effect after sensitization. Thus, sensitized and not sensitized dorsal horn neurons may respond differently to an NMDA receptor active drug. In rats nerve stimulation and halothane anaesthesia induced larger evoked responses to afferent stimulation than cutaneous stimulation and urethane anaesthesia, the AP5 effect was however similar.
2-Amino-5-phosphonovalerate↗
Shunt revisions in children--can they be avoided? Experiences from a population-based study.
BACKGROUND: Shunt failure is by far the most frequent problem in children with shunts, and most of them will experience this condition at some point in their lives. In order to identify causes of shunt failure, and to compare multi-component and one-piece shunt systems, we analyzed retrospectively all pediatric shunt procedures in our Department during an 11-year period. The study does not deal with shunt infections. METHODS: We reviewed the records of all pediatric shunting procedures between January 1986 and December 1996. RESULTS: The study included 161 children operated for hydrocephalus with a total of 431 procedures. The procedures included 124 (29%) primary insertions, 10 (2%) reinsertions and 297 (69%) revisions; 206 (69%) of the revisions were due to shunt failures, of which 74 (36%) were caused by the failure of the surgical technique (misplaced ventricular catheters, disconnected shunts, or misplaced peritoneal catheters). CONCLUSIONS: Improvement of the surgical technique may reduce the incidence of shunt failures and revisions. The results obtained in a small department like ours do not seem to differ substantially from those obtained in more specialized departments with a larger patient group. Practical measures that may reduce the risk of shunt failures are suggested.
Adolescent↗