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ACCURATE, a randomized controlled trial comparing dorsal root ganglion (DRG) stimulation to spinal cord stimulation, showed that DRG stimulation is a safe and effective therapy in individuals with lower extremity chronic pain due to complex regional pain syndrome (CRPS) type I or II. Investigators noted that DRG stimulation programming could be adjusted to minimize, or eliminate, the feeling of paresthesia while maintaining adequate pain relief. The present study explores treatment outcomes for DRG subjects who were paresthesia-free vs. those who experienced the sensation of paresthesia, as well as the factors that predicted paresthesia-free analgesia.
Learn More >We conducted a multicenter, randomized, patient and assessor-blinded, sham-controlled trial to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) in patients with neuropathic pain. Patients were randomly assigned to receive five daily sessions of active or sham rTMS of M1 corresponding to the part of the body experiencing the worst pain (500 pulses per session at 5 Hz). Responders were invited to enroll in an open-label continuous trial involving four weekly sessions of active rTMS. The primary outcome was a mean decrease in a visual analogue scale (VAS) of pain intensity (scaled 0-100 mm) measured daily during the daily sessions in an intention-to-treat population. Secondary outcomes were other pain scores, quality-of-life measures, and depression score. 144 patients were assigned to the active or sham stimulation groups. The primary outcome, mean VAS decreases, was not significantly different (p=0.58) between the active stimulation group (mean, 8.0) and the sham group (9.2) during the daily sessions. The secondary outcomes were not significantly different between two groups. The patients enrolled in the continuous weekly rTMS achieved more pain relief in the active stimulation group compared with the sham (p<0.01). No serious adverse events were observed. Five daily sessions of rTMS with stimulus conditions used in this trial were ineffective in short-term pain relief in the whole study population with various neuropathic pain. Long-term administration to the responders should be investigated for the clinical use of rTMS on neuropathic pain in the future trials.
Learn More >This study aimed to disclose differentially expressed genes (DEGs) in dorsal root ganglia (DRGs) of neuropathic pain (NP) from spared nerve injury (SNI) model, thereby identifying specific and meaningful genetic targets for the diagnosis and treatment of NP. The GSE89224 was downloaded from the GEO database. DEGs were screened using the GEO2R online tool. Functional enrichment analysis of DEGs was then performed using the DAVID and constructed using the R ggplot2 package. Protein-protein interaction (PPI) network was constructed from the STRING database and visualized in Cytoscape software. MicroRNA targeting these DEGs was obtained from the TarBase and miRTarBase database, while transcription factor (TF)-targeting DEGs were predicted from the ENCODE database, both of which utilized the visual analytics platform NetworkAnayst. Finally, a merged microRNA-TF network was constructed based on the above two networks and was then analyzed with Cytoscape. Eighty DEGs were screened, only Vstm2b and Htr3a were downregulated and 78 genes were upregulated. The real-time polymerase chain reaction was applied to validate the gene expression of the top five DEGs (Npy, Atf3, Gpr151, Sprr1a, and Cckbr) in the DRG tissue 5 days after SNI surgery. It was found that Npy, Atf3, and Sprr1a have a significant increase after SNI stimulation, while Gpr151 and Cckbr showed a slight upward trend. Functional analysis was performed on all DEGs, of which 58 biological processes were enriched by gene ontology analysis, and 11 signaling pathways were enriched by KEGG analysis. In the PPI network, Atf3, Jun, Timp, and Npy had a higher degree. Thus, combined with various bioinformatic analyses, Npy and Atf3 may serve as the prognostic and therapeutic targets of NP. Key microRNA (mmu-mir-16-5p) and TF (MEF2A) were predicted to be associated with the pathogenetic process of NP with microRNA-TF regulatory network analysis, which were also identified as key regulators in the progression of NP.
Learn More >With the shifting role of placebos, there is a need to develop animal models of placebo analgesia and elucidate the mechanisms underlying the effect. In the present study, male Sprague-Dawley rats with chronic inflammatory pain caused by complete Freund's adjuvant (CFA) underwent a series of conditioning procedures, in which morphine was associated with different cues, but they failed to induce placebo analgesia. Then, conditioning with the conditioned place preference apparatus successfully induced analgesic expectancy and placebo analgesia in naïve rats but only induced analgesic expectancy and no analgesic effect in CFA rats. Subsequently, we found enhanced c-fos expression in the nucleus accumbens and reduced expression in the anterior cingulate cortex in naïve rats while c-fos expression in the anterior cingulate cortex in CFA rats was not altered. In summary, the behavioral conditioning model demonstrated the difficulty of establishing a placebo analgesia model in rats with a pathological condition.
Learn More >Variants in the SCN1A gene are associated with a wide range of disorders including genetic epilepsy with febrile seizures plus (GEFS+), familial hemiplegic migraine (FHM), and the severe childhood epilepsy Dravet syndrome (DS). Predicting disease outcomes based on variant type remains challenging. Despite thousands of SCN1A variants being reported, only a minority has been functionally assessed. We review the functional SCN1A work performed to date, critically appraise electrophysiological measurements, compare this to in silico predictions, and relate our findings to the clinical phenotype. Our results show, regardless of the underlying phenotype, that conventional in silico software correctly predicted benign from pathogenic variants in nearly 90%, however was unable to differentiate within the disease spectrum (DS vs. GEFS+ vs. FHM). In contrast, patch-clamp data from mammalian expression systems revealed functional differences among missense variants allowing discrimination between disease severities. Those presenting with milder phenotypes retained a degree of channel function measured as residual whole-cell current, whereas those without any whole-cell current were often associated with DS (p = .024). These findings demonstrate that electrophysiological data from mammalian expression systems can serve as useful disease biomarker when evaluating SCN1A variants, particularly in view of new and emerging treatment options in DS.
Learn More >To evaluate onset of effect of galcanezumab in patients with episodic migraine.
Learn More >African Americans experience an increased burden of motor vehicle collision (MVC), post-MVC musculoskeletal pain (MSP) and Vitamin D insufficiency. In this prospective multicenter study, we tested the hypothesis that African Americans (n=133) presenting to the ED after MVC with low peritraumatic Vitamin D levels would have worse chronic MSP outcomes compared to individuals with sufficient Vitamin D. Vitamin D levels were assessed in the early aftermath of MVC via enzyme-linked immunosorbent assay, and pain severity was assessed via the 0-10 numeric rating scale at 6 weeks, 6 months and 1 year. In repeated-measures analysis, African American MVC survivors with vitamin D insufficiency experienced more severe chronic pain (β=1.18, p=0.031). In secondary analyses, we assessed for evidence that the effect of Vitamin D on post-MVC pain outcomes is mediated, at least in part, by the influence of Vitamin D on genetic variants in genes involved in immune system regulation (IL-10 and NLRP3). Genotyping was performed using a genome-wide microarray using collected DNA samples. Secondary analyses suggest that the effect of Vitamin D on post-MVC pain outcomes may be influenced by genetic variation in IL-10 and NLRP3. Further studies are needed to assess the impact of Vitamin D insufficiency on pain outcomes in African Americans experiencing MVC and other common trauma exposures, to assess factors affecting this relationship, and to assess the efficacy of administering Vitamin D in the immediate aftermath of MVC to prevent chronic pain. Such low-cost, non-opioid interventions are urgently needed to address chronic pain development following MVC.
Learn More >Pruritus is one of the most common dermatologic complaints and, as the most common dermatologic symptom, is a major contributor to frequent dermatology visits. Chronic pruritus mirrors another major medical condition faced by millions of Americans each year – chronic pain. In older literature, pain and pruritus were thought to have been conveyed by the same C fiber, and the proportion contributing to pruritus was just a small subset of this general fiber. Overall, pain and pruritus share many integral similarities. Although these sensations both initiate the body's awareness to injury, pain and itch may have evolved for sensing different damages such as a burrowing parasite or a noxious stimulus, respectively. This seems to have been validated through analyses of their pathophysiology, acute and chronic conditions, and treatment modalities. However, their symptoms and intrinsic mechanisms vary considerably. It is important to view pruritus in more of an overall, whole body experience, rather than just the sensory aspect. Future studies should investigate the psychological treatment of chronic pruritus, considering the immense similarities with its chronic pain counterpart.
Learn More >Research into acupuncture and acupressure and their application for cancer pain has been growing, but the findings have been inconsistent.
Learn More >Disruptions of lumbar intervertebral discs may lead to severe discogenic low back pain (LBP). Severe pain has a deleterious effect on physical function and quality of life. Spinal cord stimulation (SCS) is a robust treatment for many neuropathic pain conditions. New innovations may be well-suited to treat neuropathic chronic LBP, including discogenic pain. The aim of this prospective study was to determine the effect of dorsal root ganglion (DRG) stimulation for a well-selected group of patients with discogenic LBP with no history of previous back surgeries.
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