Trigger point injection therapies for chronic myofascial neck and back pain: A systematic review.

Objective: To assess the comparative effectiveness and harms of trigger point injections (TPI) for myofascial neck and back pain. Methods: Electronic literature databases were searched to identify articles pertaining to TPI for chronic myofascial neck and back pain. Searches were done from database start dates up to April 2020. Inclusion criteria were randomized controlled trials, cohorts, and case control studies. Pain, functional outcomes, and harms were extracted. Outcome time points were divided into short term (7 days to <6 weeks), intermediate term (6 weeks to â€‹< â€‹3 months), long term (3 months to â€‹< â€‹6 months), and longest term (>6 months). Quality assessment was done using the Cochrane Back Review Group (CBRG) checklist for RCTs, and the Newcastle-Ottawa Quality Assessment Scale for cohort and case control studies. Results: 14 studies met inclusion criteria. Six studies compared TPI of Botulinum toxin A (five with Onabutulinum toxin A, and one with Abobotulinum toxin A) with normal saline (NS). Two of the Onabotulinum toxin A studies showed greater pain improvement in the Onabotulinum toxin A group at short, intermediate, compared with NS. The Abobotulinum study showed pain improvement at short, intermediate, and long terms. Of note Onabotulinum toxin A was associated with improved anxiety and depression in two studies. Two studies compared Onabotulinum toxin A to local anesthetic, one to methylprednisolone, and one to dry needling (DN), all of which showed no difference. One study compared Ozone to Lidocaine and DN, and it showed no difference. Two studies compared sterile water to NS; they both found no difference in pain outcomes at the short term time point. However one of these two studies showed improved pain at intermediate, long, and longest terms in the sterile water group. Tropisetron showed no difference vs. NS. Adverse effects were mostly reported for Onabotulinum toxin A and Abobotulinum toxin A. Conclusion: Given the mixed results, we are unable to conclude whether an injectate composition is superior to another, or make recommendations in that regard. Further studies will help elucidate the ideal injectate composition and parameters.

The Effectiveness of Ketamine in Pediatric Acute Deafferentation Pain after Spinal Cord Injury.

Deafferentation pain and allodynia commonly occur after spinal cord trauma, but its treatment is often challenging. The literature on effective therapies for pediatric deafferentation pain, especially in the setting of spinal cord injury, is scarce. We report the case of a 12-year-old patient with acute allodynia after a gunshot injury to the spine. The pain was refractory to multiple analgesics, but resolved with ketamine, which also improved the patient's physical function and quality of life, a trend that continued many months after the injury. We suggest that early initiation of ketamine may be effective for acute pediatric deafferentation pain secondary to spinal cord injury, as well as preventing chronic pain states in that population.

SPT6 interacts with NSD2 and facilitates interferon-induced transcription.

The role of the histone chaperone SPT6 in mammalian cells is not fully understood. Here, we investigated the involvement of SPT6 in type I interferon (IFN)-induced transcription in murine fibroblasts. In RNA-seq analysis, Spt6 siRNA attenuates about half of ~ 200 IFN-stimulated genes (ISGs), while not affecting housekeeping genes. ISGs with high mRNA induction are more susceptible to Spt6 siRNA than those with lower levels of induction. ChIP analysis shows that SPT6 is recruited to highly inducible, Spt6 siRNA-sensitive ISGs, but not to other siRNA-insensitive ISGs. Furthermore, SPT6 recruitment is abrogated in cells lacking the histone methyltransferase NSD2. In co-IP experiments, SPT6 interacts with NSD2. In summary, SPT6 facilitates IFN-induced transcription, highlighting its critical role in gene activation.

BRD4 coordinates recruitment of pause release factor P-TEFb and the pausing complex NELF/DSIF to regulate transcription elongation of interferon-stimulated genes.

RNA polymerase II (Pol II) and the pausing complex, NELF and DSIF, are detected near the transcription start site (TSS) of many active and silent genes. Active transcription starts when the pause release factor P-TEFb is recruited to initiate productive elongation. However, the mechanism of P-TEFb recruitment and regulation of NELF/DSIF during transcription is not fully understood. We investigated this question in interferon (IFN)-stimulated transcription, focusing on BRD4, a BET family protein that interacts with P-TEFb. Besides P-TEFb, BRD4 binds to acetylated histones through the bromodomain. We found that BRD4 and P-TEFb, although not present prior to IFN treatment, were robustly recruited to IFN-stimulated genes (ISGs) after stimulation. Likewise, NELF and DSIF prior to stimulation were hardly detectable on ISGs, which were strongly recruited after IFN treatment. A shRNA-based knockdown assay of NELF revealed that it negatively regulates the passage of Pol II and DSIF across the ISGs during elongation, reducing total ISG transcript output. Analyses with a BRD4 small-molecule inhibitor showed that IFN-induced recruitment of P-TEFb and NELF/DSIF was under the control of BRD4. We suggest a model where BRD4 coordinates both positive and negative regulation of ISG elongation.

Dimerization of FIR upon FUSE DNA binding suggests a mechanism of c-myc inhibition.

c-myc is essential for cell homeostasis and growth but lethal if improperly regulated. Transcription of this oncogene is governed by the counterbalancing forces of two proteins on TFIIH--the FUSE binding protein (FBP) and the FBP-interacting repressor (FIR). FBP and FIR recognize single-stranded DNA upstream of the P1 promoter, known as FUSE, and influence transcription by oppositely regulating TFIIH at the promoter site. Size exclusion chromatography coupled with light scattering reveals that an FIR dimer binds one molecule of single-stranded DNA. The crystal structure confirms that FIR binds FUSE as a dimer, and only the N-terminal RRM domain participates in nucleic acid recognition. Site-directed mutations of conserved residues in the first RRM domain reduce FIR's affinity for FUSE, while analogous mutations in the second RRM domain either destabilize the protein or have no effect on DNA binding. Oppositely oriented DNA on parallel binding sites of the FIR dimer results in spooling of a single strand of bound DNA, and suggests a mechanism for c-myc transcriptional control.