European journal of pain : EJP
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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels contribute to stabilizing resting membrane potential, thus controlling neuron excitability. Subclasses of nociceptive neurons differ in their excitability, therefore, these channels could be a distinguishing marker. We investigated isolated dorsal root ganglion neurons from a non-rodent species, the pig, Sus scrofa domesticus. ⋯ Western blot analysis showed protein products of sizes similar to those of HCN-1 and HCN-2 channel isoforms. Functionally, in patch-clamp experiments, some neurons were unresponsive to membrane hyperpolarization, thus, probably lacking HCN channels. In conclusion, in porcine dorsal root ganglion neurons there is a subset of capsaicin-positive, IB4-negative neurons lacking HCN-1 and/or HCN-2 channel isoforms.
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Loss of spinal inhibitory mechanisms is thought to contribute to the pathophysiology of abnormal pain states, including neuropathic pain. By using an evoked spinal field potential technique, the hypothesis was tested here that decreased spinal GABAergic control underlies poor response to morphine (MOR) that often accompanies neuropathic pain. Therefore, field potentials evoked by electrical peripheral nerve stimulation during spinal superfusion with MOR were recorded in rats rendered neuropathic by a spinal nerve ligation (SNL) procedure, and compared to responses recorded in naïve rats. ⋯ Two-way analysis of variance revealed no interaction of MOR with either CGP354348 (p = 0.42) or BIC (p = 0.14). Evidence is presented here that injury to the primary afferent system results in significant changes in the ability of spinal MOR to depress field potentials evoked by peripheral input. However, the present findings do not support a pathogenic role for decreased GABAergic inhibition in such changes.
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Randomized Controlled Trial Multicenter Study
Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients.
Neuropathic pain remains one of the most challenging pain syndromes; under-diagnosed, poorly managed and associated with significant co-morbidity. With standard therapeutic treatments, responders rarely exceed 50% pain relief and the majority suffer from residual pain. Titration to optimum dose is often limited by dose-related adverse events. ⋯ This study provides the first evidence that co-administration of prolonged-release oxycodone and existing gabapentin therapy has a clinically meaningful effect in painful diabetic neuropathy.
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Comparative Study
A comparison of the relationship between depression, perceived disability, and physical performance in persons with chronic pain.
This study examined the relationships between self-report of depressive symptoms, perceived disability, and physical performance among 267 persons with chronic pain. Prior research has reported a relationship between depression and disability using self-report measures. However, self-report instruments may be prone to biases associated with depression as depressed persons with pain may have an exaggerated negative view of their level of function. ⋯ The magnitude of the relationships between depression and self-report and functional activity were similar, suggesting that a self-report bias associated with depression is not responsible for an observed relationship between depression and disability. Physiologic effort partially mediated the relationship between depression and physical performance. The findings further highlight the importance of depression in the experience of chronic pain.
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Randomized Controlled Trial
Effects of simultaneous dual-site TENS stimulation on experimental pain.
Transcutaneous electrical nerve stimulation (TENS) is commonly used for pain relief. However, little robust research exists regarding the combination of parameters required to provide effective doses. This study investigated the hypoalgesic effects of different parameter combinations, applied simultaneously at two sites (segmental and extrasegmental), on pressure pain threshold (PPT) in pain-free humans. ⋯ Those groups using high-intensity stimulation at the segmental stimulation sites showed significantly greater hypoalgesia than placebo (p < 0.025 in each case). The largest hypoalgesic effect was for simultaneous high-intensity stimulation at segmental and extrasegmental sites, using different frequencies. These results reaffirm that high-intensity stimulation (regardless of frequency) is of fundamental importance in effective dosage.