Pain
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Clinical Trial
Influence of repeated painful procedures and sucrose analgesia on the development of hyperalgesia in newborn infants.
This study determined the effects of cumulative exposure to painful needle procedures and sucrose analgesia on the development of remote hyperalgesia in newborn infants, defined as an increase in response to a normally painful stimulus at a site distal from the site of injury. One-hundred and twenty healthy newborns and 120 healthy newborn infants of diabetic mothers equally randomized to sucrose analgesia or placebo prior to all needle procedures in the first two days after birth were divided into two exposure groups according to number of needle procedures they had undergone [high (> or =5) or low (< or =4)] using the median cut-off technique. Compared to the low exposure group, infants in the high exposure group had a higher pain response during a subsequent venipuncture distal to the site of previous injury, assessed by the Premature Infant Pain Profile (PIPP) [7.1 vs. 8.4; p=0.012] and Visual Analog Scale (VAS) [2.5 cm vs. 3.2 cm; p=0.047], and a trend for longer cry duration [25.7 s vs. 33.8 s; p=0.171]. ⋯ Sucrose reduced PIPP, VAS, and cry duration scores during venipuncture, but did not prevent hyperalgesia (p>0.05). There was a preponderance of infants of diabetic mothers in the high exposure group; however, the analysis did not demonstrate this to be a confounding factor. In conclusion, sucrose analgesia for repeated painful procedures in the first day of life does not prevent development of remote hyperalgesia in newborns.
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Clinical Trial
Ultrasound guided, painful electrical stimulation of lumbar facet joint structures: an experimental model of acute low back pain.
Quantitative sensory testing has indicated generalized muscle hyperalgesia in patients with chronic low back pain. The temporal development of such hyperalgesia is not well understood. The aim of the present study was to demonstrate whether generalized muscle hyperalgesia can develop within minutes of acute low back pain using a new experimental model of lumbar facet joint pain. ⋯ Electrical facet joint stimulation induced low back pain and pain referral into the anterior leg, ipsilaterally, proximal to the knee, similar to what is observed clinically. Pressure pain thresholds did not change significantly before, during and after facet joint stimulation. In conclusion, we describe a novel model of acute experimental low back pain and demonstrate that generalized hyperalgesia did not develop within minutes of acute low back pain.
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Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4-6 h after administration. The causative mechanisms are not known, but the long delay leaves room for a central effect, such as a change in neuronal excitability and synaptic transmission of various CNS areas involved in pain and behaviour including trigeminal nucleus caudalis and monoaminergic brain stem nuclei. To explore the central action of NTG, we have studied its effects on amplitude and habituation of the nociceptive blink reflex (nBR) and the visual evoked potential (VEP) before, 1 h and 4 h after administration of NTG (1.2 mg sublingual) or placebo (vehicle sublingual) in two groups of 10 healthy volunteers. ⋯ There were no significant VEP changes in subjects who received sublingual placebo. In conclusion, we found that in healthy subjects sublingual NTG, but not its vehicle, induces changes in a trigeminal nociceptive reflex and an evoked cortical response which are comparable to those found immediately before and during an attack of migraine. These changes could be relevant for the attack-triggering effect of NTG in migraineurs.
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Clinical Trial
Can extremely low or high morphine formation from codeine be predicted prior to therapy initiation?
Activation of codeine by O-demethylation into morphine is a prerequisite for its analgesic effects and severe toxicity. Identifying patients in whom morphine is formed either at extremely low or at extremely high amounts may improve efficacy and safety of codeine therapy. To assess how well this identification is possible, we compared the performance of current CYP2D6 phenotype association systems (traditional genotype-based classification, a recently proposed CYP2D6 activity score, and the plasma dextromethorphan metabolic ratio) in 57 healthy Caucasians after oral administration of 30 mg dextromethorphan hydrobromide or 50 mg codeine. ⋯ However, satisfactory prediction (87.5%) of high morphine formation was only achieved when combining genotyping with phenotyping. In conclusion, insufficient morphine formation from codeine and thus likely failure of analgesia can currently be well predicted. However, to make codeine therapy safe, extremely high morphine formation has to be predicted as well, which has to be obtained at the effort of combining genotyping with phenotyping.
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A recent study described for the first time a patient group that suffered from spontaneous chronic pain and from recurrent herpes simplex virus (HSV) infections. The patients had pain in widespread areas on one side of the body and were--due to subtle immunological abnormalities--susceptible to HSV infections. Although the clinical features of the pain suggested involvement of the central nervous system, supporting evidence for this was lacking. ⋯ We found functional changes in the patients' central pain circuitry: activation to heat pain was weaker than in control subjects in the insular cortices, anterior cingulate cortex (ACC), and thalamus, while the activations to innocuous tactile stimuli were similar in both groups. Gray matter density was decreased in the patients' frontal and prefrontal cortices and in the ACC. The observed functional and structural changes in the central pain circuitry, together with the clinical features of the chronic pain support the hypothesis for central involvement in the development of chronic pain in these patients.