84 research outputs found
Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery
Human pain models are useful in the assessing the analgesic effect of
drugs, providing information about a drug's pharmacology and identify
potentially suitable therapeutic populations. The need to use a
comprehensive battery of pain models is highlighted by studies whereby
only a single pain model, thought to relate to the clinical situation,
demonstrates lack of efficacy. No single experimental model can mimic
the complex nature of clinical pain. The integrated, multi-modal pain
task battery presented here encompasses the electrical stimulation task,
pressure stimulation task, cold pressor task, the UVB inflammatory
model which includes a thermal task and a paradigm for inhibitory
conditioned pain modulation. These human pain models have been tested
for predicative validity and reliability both in their own right and in
combination, and can be used repeatedly, quickly, in short succession,
with minimum burden for the subject and with a modest quantity of
equipment. This allows a drug to be fully characterized and profiled for
analgesic effect which is especially useful for drugs with a novel or
untested mechanism of action. Perioperative Medicine: Efficacy, Safety and Outcom
Pharmacokinetics and pharmacodynamics of multiple doses of BG00010, a neurotrophic factor with anti-hyperalgesic effects, in patients with sciatica
AIMS: BG00010
is a protein in the glial cell line-derived neurotrophic factor (GDNF)
family. It is a selective ligand for the GDNF family receptor alpha-3
(GFRα3) co-receptor that normalizes cellular changes resulting from
damage or disease, and potentially alleviates neuropathic pain. The main
objectives of this study were to evaluate the pharmacokinetic and
safety profiles and to determine the effects on pain of ascending doses
of intravenous injections of BG00010 in patients with sciatica.METHODS: This
was a randomized, blinded, placebo-controlled multiple-dose study in
subjects with sciatica. In Part I (16 patients), four IV dose levels
were examined (50, 150, 400, 800 μg kg(-1) ) and in Part II (12
patients), three dose levels were examined (400, 600 and 1200 μg kg(-1)
). Safety and efficacy assessments were used as endpoints.RESULTS: The
BG00010 concentration-time data indicated relatively low inter-patient
variability and there was a dose-dependent (not dose-proportional)
increase in serum exposure from 150 to 1200 μg kg(-1) . The effective
half-life was between 40 and 60Â h. The most frequently occurring adverse
events (AEs) reported by patients receiving BG00010 were headache
(67-83%), feeling hot (50-100%), and pruritus (42-67%). Most AEs were
mild; no serious AEs or AEs leading to discontinuation occurred. Higher
dose regimens of BG00010 resulted in greater pain reduction than placebo
or lower dose regimens, although a clear dose-response relationship was
not seen.CONCLUSIONS: The
pharmacokinetic profile of BG00010 was characterized by low
intra-patient variability. These data from a small sample suggest that
BG00010 may have a benefit for patients with sciatica.TRIAL REGISTRATION: ClinicalTrials.gov NCT00961766 NCT01405833.Perioperative Medicine: Efficacy, Safety and Outcom
Influence of nitrogen on diamond growth in oxyacetylene combustion chemical vapor deposition
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Immigration, Jobs and Employment Protection: Evidence from Europe before and during the Great Recession
The use of a battery of evoked pain models in early phase drug development
Drug development scientists are on a search for suitable
biomarkers that can assist in predicting the therapeutic potential of
analgesic medication and, therefore, it’s efficacy in the target population.
This is particularly appropriate for human pain where models can assist to
bridge the preclinical and clinical findings. These models can provide
valuable information about the mechanism of action of existing and new drugs.
However, a single human pain model cannot be used exclusively to screen the
pharmacological mechanism of a compound as it inherently only tests a single
mechanism.
In this thesis the performance of a battery of pain models (PainCart) was
investigated. Three main topics were investigated. (1) The validation of the
PainCart was described in which the effects of different classes of
analgesics on this battery of pain models were explored. (2) The PainCart was
used in different chronic pain populations. (3) The performance of the
battery during the development of new analgesic compounds was studied.
The battery of pain models can act as biomarker to assess the effect of
analgesics on pain. It can be used to benchmark analgesic properties of new
drugs against established analgesics in early phase clinical studies.
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The use of a battery of evoked pain models in early phase drug development
Drug development scientists are on a search for suitable
biomarkers that can assist in predicting the therapeutic potential of
analgesic medication and, therefore, it’s efficacy in the target population.
This is particularly appropriate for human pain where models can assist to
bridge the preclinical and clinical findings. These models can provide
valuable information about the mechanism of action of existing and new drugs.
However, a single human pain model cannot be used exclusively to screen the
pharmacological mechanism of a compound as it inherently only tests a single
mechanism.
In this thesis the performance of a battery of pain models (PainCart) was
investigated. Three main topics were investigated. (1) The validation of the
PainCart was described in which the effects of different classes of
analgesics on this battery of pain models were explored. (2) The PainCart was
used in different chronic pain populations. (3) The performance of the
battery during the development of new analgesic compounds was studied.
The battery of pain models can act as biomarker to assess the effect of
analgesics on pain. It can be used to benchmark analgesic properties of new
drugs against established analgesics in early phase clinical studies.
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Blood pressure augmentation to supra normal levels to improve oxygenation in COVID-19
Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care
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