European journal of pain : EJP
-
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.
-
The mechanism underlying discogenic low-back pain is unclear. It is difficult to explain this type of pain by the segmental innervation theory because the groin area is innervated by the genitofemoral or ilioinguinal nerves, which are the terminal branches of the L1 or L2 spinal nerves. Recently, some studies have indicated that sympathetic trunks are closely related to discogenic low-back pain. ⋯ We demonstrated that FG-labeled SP-ir neurons in L2 DRGs decreased when FG was applied to the ventral or dorsal portions of L5-6 discs. The results indicated that the L2 ramus communicans played an important role in the afferent pathway of both the ventral and dorsal portions of the L5-6 disc. Nociceptive information from the L5-6 disc may be transmitted mainly by L2 DRG neurons through the L2 ramus communicans.
-
Mice lacking the serotonin-transporter (5-HTT-/- mice) develop reduced thermal hyperalgesia after nerve injury, concomitant with reduced serotonin (5-HT) levels in nervous tissue. Here we investigated pain behaviour in 5-HTT-/- mice compared to their wild type littermates after hind paw inflammation induced by complete Freund's adjuvant (CFA). We used standard tests for pain behaviour, high performance liquid chromatography for measurement of 5-HT, and immunohistochemistry of hind paw skin tissue and L5 dorsal root ganglia (DRG) to measure local inflammation and nerve injury. ⋯ Accordingly, a higher number of injured DRG neurons was identified by activating transcription factor 3 (ATF3) staining in 5-HTT-/- mice after CFA. We conclude that the phenotype of 5-HTT-/- mice leads to reduced inflammatory pain due to reduced tissue 5-HT levels and to greater peripheral nerve injury after inflammation. Human variants of the 5-HTT genotypes might be part of the factors determining the extent of nerve injury and hyperalgesia in inflammation.
-
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.
-
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.