Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity
Rare pain-insensitive individuals offer unique insights into how pain circuits function and have led to the development of new strategies for pain control. We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region. The deletion region can be inclusive or exclusive of the brain-derived neurotrophic factor (BDNF) gene, a crucial trophic factor for nociceptive afferents. Nociceptive responses assessed by quantitative sensory testing demonstrated reduced pain sensitivity only in the WAGR subjects whose deletion boundaries included the BDNF gene. Corresponding behavioral assessments were made in heterozygous Bdnf knockout rats to examine the specific role of Bdnf. These analogous experiments revealed impairment of Aδ- and C-fiber-mediated heat nociception, determined by acute nociceptive thermal stimuli, and in aversive behaviors evoked when the rats were placed on a hot plate. Similar results were obtained for C-fiber-mediated cold responses and cold avoidance on a cold-plate device. Together, these results suggested a blunted responsiveness to aversive stimuli. Our parallel observations in humans and rats show that hemizygous deletion of the BDNF gene reduces pain sensitivity and establishes BDNF as a determinant of nociceptive sensitivity.
Publication date: Available online 20 July 2019Source: Best Practice &Research Clinical AnaesthesiologyAuthor(s): Mark R. Jones, Matthew B. Novitch, Sudipta Sen, Nadia Hernandez, Johanna Blair De Haan, Rebecca A. Budish, Christopher Bailey, Joseph Ragusa, Pankaj Thakur, Vwaire Orhurhu, Ivan Urits, Elyse M. Cornett, Alan David KayeAbstractSurgeries and chronic pain states of the upper extremity are quite common and pose unique challenges for the clinical anesthesiology and pain specialists. Most innervation of the upper extremity involves the brachial plexus. The four most common brachial plexus blocks performed in clin...
ConclusionOver 60% of Medicare patients with asthma continued and were adherent to omalizumab over 12-month follow-up. Patient age, LIS status, and the numbers of evaluation and management physician visits were among factors associated with treatment adherence and discontinuation.
Conclusions and implicationsThe predictive patterns of phonological awareness on reading fluency are complex and depend on many factors, while vocabulary knowledge is an important and consistent predictor for both deaf and hearing children.
Authors: PMID: 31322038 [PubMed - in process]
This study investigated the prevalence of depression and explored fatigue, QOL, and pain that is associated with depression in patients on first admission to a hematologic oncology unit. METHODS: This descriptive study measured depression, QOL, and fatigue with the Patient Health Questionnaire-9, the Functional Assessment of Cancer Therapy (FACT)-General, and the FACT-Anemia scale, respectively. Pain levels were examined with a numeric rating scale. FINDINGS: 58 patients participated; 17 reported moderate to severe depression, which highly correlated with fatigue, QOL, and pain. Among all factors, multivariate an...
Publication date: Available online 6 July 2019Source: Journal of Molecular BiologyAuthor(s): Jacob Gordon, Monica C. Pillon, Robin E. StanleyAbstractThe ribosome plays a universal role in translating the cellular proteome. Defects in the ribosome assembly factor Las1L are associated with congenital lethal motor neuron disease and X-linked intellectual disability disorders, yet its role in processing precursor ribosomal RNA (pre-rRNA) is largely unclear. The Las1L endoribonuclease associates with the Nol9 polynucleotide kinase to form the internal transcribed spacer 2 (ITS2) pre-rRNA endonuclease–kinase machinery. Tog...
CONCLUSION: Microvascular decompression may be more effective than radiofrequency thermocoagulation for patients with classical trigeminal neuralgia with concomitant persistent facial pain. PMID: 31321761 [PubMed - in process]
Authors: Poduval G PMID: 31321949 [PubMed - in process]
Conclusions: Very young