European journal of pain : EJP
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Insensitivity to pain is a rare disorder that is commonly associated with Hereditary Sensory and Autonomic Neuropathies (HSAN I-V) resulting often in autonomic dysfunction and premature death. Very few individuals have been reported with pain insensitivity lacking such autonomic neuropathies. We performed genetic, neurologic, psychological, and psychophysical evaluations in such an individual (OMIM 243000) and her first degree relatives. ⋯ Congenital insensitivity to pain in our IC was associated with two novel SCN9A mutations which most likely resulted in a Nav1.7 channelopathy. However, in contrast to individuals with other SCN9A mutations, the observed pain insensitivity was relative and not absolute, which may be consistent with hypomorphic effects of one or both mutations. The ability to sense at least some danger signals may be advantageous and ameliorate the otherwise increased morbidity and mortality of some individuals with congenital insensitivity to pain.
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This study is part of a research program to reach consensus on an international cancer pain classification system. A confirmative and explorative approach was applied to investigate which of the variables identified in the literature, by experts and patients that are associated with pain. ⋯ Breakthrough pain and psychological distress were confirmed as key variables of a future classification system. Candidate variables were: sleep, opioid dose, pain mechanism, use of non-opioids, pain localisation, cancer diagnosis, location of metastases, and addiction.
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Clinical Trial
Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects.
Previous reports have demonstrated greater antinociception following administration of a buprenorphine/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. ⋯ Minimal respiratory depression and few adverse events were observed in all conditions. These findings suggest that, as previously described with naloxone, the addition of ultra-low dose naltrexone can enhance the antinociceptive effect of buprenorphine in humans. This potentiation is dose-ratio dependent and occurs without a concomitant increase in adverse effects.
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Randomized Controlled Trial
Population pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief of chronic pain.
Pharmacological treatment of chronic (neuropathic) pain is often disappointing. In order to enhance our insight in the complex interaction between analgesic drug and chronic pain relief, we performed a pharmacokinetic-pharmacodynamic (PK-PD) modeling study on the effect of S(+)-ketamine on pain scores in Complex Regional Pain Syndrome type 1 (CRPS-1) patients. ⋯ Long-term S(+)-ketamine treatment is effective in causing pain relief in CRPS-1 patients with analgesia outlasting the treatment period by 50 days. These data suggest that ketamine initiated a cascade of events, including desensitization of excitatory receptor systems in the central nervous system, which persisted but slowly abated when ketamine molecules were no longer present.
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Back pain is common and some sufferers consult GPs, yet many sufferers develop persistent problems. Combining information on risk of persistence and prognostic indicator prevalence provides more information on potential intervention targets than risk estimates alone. ⋯ Several factors increased risk of poor outcome in back pain patients, notably high pain and unemployment. These risks in combination with high prevalence of risk factors in this population distinguish factors that can help identify targets or sub-groups for intervention.