Rolf Karlsten

The incidence of chronic post-sternotomy pain after cardiac surgery : a prospective study

Background: Post‐sternotomy pain is sometimes a sequela of cardiac surgery. The incidence, characteristics and clinical course of post‐sternotomy pain are not well known. The aim of our study was to determine the incidence of chronic post‐sternotomy pain in patients undergoing sternotomy for cardiac surgery in general and according to the specific surgical procedure.

Central nervous system effects of subdissociative doses of (S)‐ketamine are related to plasma and brain concentrations measured with positron emission tomography in healthy volunteers

Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)‐ketamine were measured in a randomized, double‐blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes. Specific binding in the brain was assessed by simultaneous administration of (S)‐[N‐methyl‐11C]ketamine quantified by positron emission tomography. High radioactivities in the brain corresponded to regional distribution of N‐methyl‐D‐aspartate receptor complexes. A significant and dose‐dependent reduction of binding was measured as a result of displacement of (S)‐[N‐methyl‐11C]ketamine. Memory impairment and psychotomimetic effects were related to dose, plasma concentration 4 minutes after administration, and decreased regional binding of (S)‐ketamine in the brain and were consistently seen at plasma and maximum regional brain (S)‐ketamine concentrations higher than 70 and 500 ng/ml, respectively. The magnitude of specific binding of (S)‐ketamine, measured with positron emission tomography, can be related directly to drug effects.

The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury

Background:  Pain following spinal cord injury (SCI) is a therapeutic challenge. Only a few treatments have been assessed in randomized, controlled trials. The primary objective of the present study was to examine the analgesic effect of ketamine and lidocaine in a group of patients with neuropathic pain below the level of spinal cord injury. We also wanted to assess sensory abnormalities to see if this could help us to identify responders and if treatments resulted in changes of sensibility.

Effects of intrathecal injection of the adenosine receptor agonists R-phenylisopropyl-adenosine and N-ethylcarboxamide-adenosine on nociception and motor function in the rat.

R-phenylisopropyl-adenosine, which has an affinity for the adenosine A1 receptor higher than that for the A2 receptor, and N-ethylcarboxamide-adenosine, which has near equal affinity for the A1 and A2 receptors, were injected intrathecally into rats to evaluate differences in antinociceptive effect and motor impairment. Using the tail-immersion test, both compounds had antinociceptive effects. Motor function was evaluated during spontaneous movement in a free space. N-ethylcarboxamide-adenosine rapidly impaired motor function even after low intrathecal doses. R-phenylisopropyl-adenosine also induced motor impairment, but only after high intrathecal doses, and onset was much slower. These results suggest that the receptor selectivity of R-phenylisopropyl-adenosine is diminished at higher doses and that the motor impairment is an A2-receptor-mediated effect. A selective A1 receptor agonist, e.g., R-phenylisopropyl-adenosine, which produces a good antinociceptive effect without motor impairment, is more promising as a drug of possible use for the future treatment of clinical pain.

The effectiveness of intravenous ketamine and lidocaine on peripheral neuropathic pain

Background:  Neuropathic pain is often severe and resistant to pharmacological treatment. The aims of the present study were to assess the analgesic effect of ketamine and lidocaine and to investigate if measurement of different variables of sensibility could be used to identify responders. We also wanted to study if treatment resulted in changes of sensibility.

The NMDA antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) has antinociceptive effect after intrathecal injection in the rat

&NA; This behavioral study was performed in order to delineate the antinociceptive effects of and the influence on motor function of a highly potent, competitive NMDA receptor antagonist 3‐(2‐carboxypiperazin‐4yl) propyl‐1‐phosphonic acid (CPP). After intrathecal (i.t.) administration of CPP to chronically catheterized rats, antinociception was studied in 3 different nociceptive tests: the tail‐flick test, the hot‐plate test, and the formalin test. The lowest dose producing visible motor dysfunction was 1 nmol, with 2 of 8 animals showing slight ataxia. Dose‐related motor dysfunction and apparent sedation was present after 5 and 10 nmol. Dose‐related antinociception was evident in the thermal tests following doses that produced little or no motor dysfunction. In the tail‐flick test, the antinociceptive effect was attenuated at higher doses, resulting in a bell‐shaped dose‐response relationship. Dose‐related antinociception was found in both the first and second phase of the formalin test following doses from 0.25 up to 1 nmol. The present study shows that the competitive NMDA antagonist CPP has an antinociceptive effect in doses that do not affect motor function. Furthermore, antinociception was evident in both phasic and tonic nociceptive tests. Finally, the dose‐response relationship in the tail‐flick test was bell‐shaped. As discussed this indicates that NMDA receptors may be involved in functionally divergent nociceptive systems.

Recommended guidelines for reporting on emergency medical dispatch when conducting research in emergency medicine: The Utstein style☆

OBJECTIVES To establish a uniform framework describing the system and organisation of emergency medical response centres and the process of emergency medical dispatching (EMD) when reporting results from studies in emergency medicine and prehospital care. DESIGN AND RESULTS In September 2005 a task force of 22 experts from 12 countries met in Stavanger; Norway at the Utstein Abbey to review data and establish a common terminology for medical dispatch centres including core and optional data to be used for health monitoring, benchmarking and future research.

The antinociceptive effect of intrathecally administered adenosine analogs in mice correlates with the affinity for the A1-adenosine receptor.

In the present study, the antinociceptive effects after intrathecal injection of each of 6 N6-substituted adenosine analogs and of 2-phenylaminoadenosine were compared with the affinity for the A1- and A2-adenosine receptors. Adenosine analogs, substituted in the N6-position, had stereoselective structure-dependent antinociceptive effects in the tail flick and hot plate assays after intrathecal injection in mice. The antinociceptive activity for N6-R- and S-phenylisopropyladenosine (R- and S-PIA), N6-R- and S-1-phenylethyladenosine, N6-1,1-dimethyl-2-phenylethyladenosine (methylPIA), and N6-cyclooctyladenosine correlated with the affinity for central A1-adenosine receptors. An adenosine analog, 2-phenylaminoadenosine, selective for A2-adenosine receptors was inactive in the two tests. These results strongly suggest that spinal A1-adenosine receptors are responsible for the antinociceptive effects of adenosine and its analogs after intrathecal injection.

Intervention with Spinal NMDA, Adenosine, and NO Systems for Pain Modulation

Understanding of the complex pharmacology of the spinal cord may lead to rational advances in pain treatment. It appears that a number of specific neurochemical mechanisms exist, by which spinally administered receptor selective agents may modify nociceptive transmission. Spinal administration of pure competitive N-methyl-D-aspartate (NMDA) antagonists affects only hyperpathic pain components, i.e. with signs of central sensitization, and most probably has a very limited role in postoperative pain treatment. On the other hand, it is well established that the non-competitive NMDA-antagonist ketamine gives good postoperative analgesia, probably by cerebral mechanisms also affecting other sensory modalities. Pure adenosine A1-receptor agonism at the spinal level mainly affects sensory allodynia to vibration, and is probably no alternative for postoperative pain treatment. In contrast, i.v. infusions of the non-selective A1/A2-receptor agonist adenosine given during a surgical procedure seem to decrease postoperative pain and requirements for postoperative analgesia. This apparent contradiction must be analysed further. Several drugs commonly used to treat postoperative pain, such as opioids, NSAIDs, ketamine and paracetamol, are linked to nitric oxide (NO) in their mechanism of action. The biosynthesis of NO in the central nervous system (CNS) is tonically involved in the nociceptive processing.

How Do Drugs Relieve Neurogenic Pain

SummaryNeurogenic pain is experienced by about 1% of the population. The efficacy of drug treatment for this condition has been poorly evaluated, and only recently have certain treatments been shown to have significant analgesic effects. Monotherapy with topical agents such as capsaicin is not usually sufficient. Oral agents that have proven effective in treating neurogenic pain states include tricyclic antidepressants, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors and anticonvulsants. Local anaesthetics, administered intravenously, have been reported to relieve pain in selected patients, but data from controlled trials are sparse.Multiple mechanisms contribute to the generation of neurogenic pain. In the future, drug treatment for neurogenic pain is likely to target these mechanisms. Recent studies have shown that N-methyl-D-aspartate (NMDA) receptor antagonists, adenosine receptor agonists and nitric oxide synthase inhibitors may become useful in the treatment of neurogenic pain.