Articles: pain-clinics.
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Human experimental pain models are widely used to study drug effects under controlled conditions, but they require further optimization to better reflect clinical pain conditions. To this end, we measured experimentally induced pain in 110 (46 men) healthy volunteers. The quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain) was applied on untreated ("control") and topical capsaicin-hypersensitized ("test") skin. ⋯ Inclusion in the respective clusters was predictable at a cross-validated accuracy of 86.9% by a classification and regression tree comprising 3 QST parameters (mechanical pain sensitivity, wind-up ratio, and z-transformed thermal sensory limen) from the control sites. Thus, we found that topical capsaicin partly induced the desired clinical pattern of neuropathic pain in a preselectable subgroup of healthy subjects to a degree that fuels expectations that experimental pain models can be optimized toward mimicking clinical pain. The subjects, therefore, qualify for enrollment in analgesic drug studies that use highly selected cohorts to enhance predictivity for clinical analgesia.
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Patients with chronic pain usually suffer from cognitive impairment, with memory deterioration being the most common deficit that affects daily functioning and quality of life. The causes for this impairment are not clear despite intensive clinical studies. Few studies have evaluated impaired learning using animal models of persistent pain. ⋯ The results of this study suggest that trigeminal neuralgia induced by cobra venom in adult rats can impair spatial learning and memory function over time and results in demonstrable changes in the ultrastructure of the medulla oblongata. This new animal model may be useful for future studies on the effect of chronic pain on learning and cognition.
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Intradiscal biacuplasty (IDB) is a novel heating therapy using cooled radiofrequency (RF), which may offer relief for discogenic pain. Effective neuroablation may be achieved intradiscally at higher lesion temperatures. The safety of intradiscal heating at elevated temperatures using cooled RF has never been reported. ⋯ The modified treatment paradigm showed intradiscal heating is achieved and is concentrated in the posterior annulus, suggesting minimal risk of thermal damage to the neighboring neural structures. Clinical benefits should be evaluated.
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Randomized Controlled Trial
Spinal cord stimulation attenuates temporal summation in patients with neuropathic pain.
Evidence has shown that electrical stimulation at the dorsal columns attenuated the "wind-up" phenomenon in dorsal horn neurons in nerve-injured rats. This study was aimed to test the effect of spinal cord stimulation (SCS) on temporal summation (TS), the clinical correlate of the wind-up phenomenon in patients with radicular leg pain. Eighteen patients with SCS implants were tested both 30 minutes after SCS activation ("ON") and 2 hours after turning it off ("OFF"), in a random order. ⋯ In the nonpainful leg, SCS activation failed to produce an effect on TS (24 ± 20 vs 21 ± 24 in SCS "OFF" and "ON", respectively; P = 0.277). In contrast, a significant decrease in the magnitude of TS in the affected leg was observed in response to SCS activation (from 32 ± 33 to 19 ± 24; P = 0.017). These results suggest that attenuation of TS, which likely represents suppression of hyperexcitability in spinal cord neurons, is a possible mechanism underlying SCS analgesia in patients with neuropathic pain.
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To begin to address the problem of heterogeneity of distribution of oxycodone (OC) in humans, we developed an organ-specific microcirculatory capillary-tissue exchange 2-compartment model for studying regional OC mass transport. ⋯ Organ-specific OC mass transport kinetics provide new information for OC dosing in pain management. The model promotes patient safety in opioid prescribing because it allows predictions to be made about the relative contribution that OC recycling makes to circulating OC levels. The model indicates that pharmacologic modulation of the microcirculation may give way to site-specific delivery of opioids in the future. Our study demonstrates that translation of bench in silico research data into clinical practice, although still challenging, is feasible and can assist in OC dose regimen design for patient safety.