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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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.
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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.
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Randomized Controlled Trial Comparative Study
The effect of electroacupuncture on opioid-like medication consumption by chronic pain patients: a pilot randomized controlled clinical trial.
Opioid-like medications (OLM) are commonly used by patients with various types of chronic pain, but their long-term benefit is questionable. Electroacupuncture (EA) has been previously shown beneficial in reducing post-operative acute OLM consumption. In this pilot randomized controlled trial, the effect of EA on OLM usage and associated side effects in chronic pain patients was evaluated. ⋯ At the end of treatment period, reductions of OLM consumption in REA and SEA were 39% and 25%, respectively (p=0.056), but this effect did not last more than 8 weeks after treatment. There was no difference between the two groups with respect to reduction of side effects and pain and the improvement of depression and quality of life. In conclusion, REA demonstrates promising short-term reduction of OLM for participants with chronic non-malignant pain, but such effect needs to be confirmed by trials with adequate sample sizes.
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Phosphorylation of the N-methyl-D-aspartate (NMDA) receptor NR1 subunit (pNR1) in the spinal cord is associated with increased neuronal responsiveness, which underlies the process of central sensitization. Because of the importance of NR1 in central sensitization, the first goal of this study was to examine both time- and lamina-dependent changes in spinal NR1 and pNR1 expression in a chronic constriction injury (CCI) model of neuropathic pain. Increased excitability of capsaicin sensitive primary afferents (CSPAs), which express TRPV1 receptors, also contributes to central sensitization. ⋯ Pretreatment with RTX (0.3mg/kg, s.c. in the scruff of the neck or intraplantar) 2 days prior to CCI completely prevented induction of thermal hyperalgesia, but not mechanical allodynia in neuropathic rats. Interestingly, RTX treatment significantly attenuated the CCI-induced upregulation of NR1 and pNR1 in spinal laminae I-II and V-VI, but not laminae III-IV as compared with that of vehicle-treated CCI rats. These findings demonstrate that the increased expression of NR1 and pNR1 in spinal laminae I-II and V-VI is dependent on activation of CSPAs, which ultimately contribute to the development of thermal hyperalgesia in neuropathic rats.