Rejected

Central neuropathic pain is the main symptom caused by spinal cord lesion in relapsing-remitting multiple sclerosis (RRMS), but its management is still not effective. The transient receptor potential ankyrin 1 (TRPA1) is a pain detecting ion channel involved in neuropathic pain development. Thus, the aim of our study was to evaluate the role of TRPA1 in central neuropathic nociception induced by relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) mouse model. In this model, we observed the development of similar clinical conditions of RRMS in C57BL/6 female mice through RR-EAE using MOG antigen and Quil A adjuvant. At the thirty-fifth day post-induction, C57BL/6 female mice demonstrated alteration in the RR-EAE score without motor impairment, mechanical and cold allodynia. Also, significative changes in demyelinating (Mog and olig-1) and neuroinflammatory (Iba1, Gfap and Tnfa) markers were observed, but this model did not alter Trpa1 RNA expression levels in the spinal cord. The hydrogen peroxide and 4-hydroxynonenal levels (TRPA1 agonists) were increased in RR-EAE induced mice, as well as the NADPH oxidase activity. The intragastric treatment of RR-EAE induced mice with TRPA1 antagonists (HC-030031 and A-967079) and antioxidant (α-lipoic acid and apocynin) caused an antiallodynic effect. Moreover, the intrathecal administration of TRPA1 antisense oligonucleotide, HC-030031, α-lipoic acid, and apocynin transiently attenuated mechanical and cold allodynia. Thus, TRPA1 plays a key role in the induction of neuropathic pain in this model of RR-EAE and can be a possible target for investigating the development of pain in RRMS patients.

The voltage sodium channel 1.8 (Na1.8) in the dorsal root ganglion (DRG) neurons contributes to the initiation and development of chronic inflammatory and neuropathic pain. However, an effective intervention on Na1.8 remains to be studied in pre-clinical research and clinical trials. In this study, we aimed to investigate whether transcription factor 4 (TCF4) overexpression represses Na1.8 expression in DRG neurons, thus preventing the development of chronic pain. Using chromatin immunoprecipitation (CHIP), we verified the interaction of TCF4 and sodium voltage-gated channel alpha subunit 10A (SCN10A) enhancer in HEK293 cells and rat DRG neurons. Using a dual luciferase reporter assay, we confirmed the transcriptional inhibition of TCF4 on SCN10A promoter in vitro. To investigate the regulation of TCF4 on Nav1.8, we then upregulated TCF4 expression by intrathecally delivering an overexpression of recombinant adeno-associated virus (rAAV) in the Complete Freund's adjuvant (CFA)-induced inflammatory pain model and spared nerve injury (SNI)-induced neuropathic pain model. By using a quantitative polymerase chain reaction (qPCR), western blot, and immunostaining, we evaluated Na1.8 expression after a noxious stimulation and the application of the TCF4 overexpression virus. We showed that the intrathecal delivery of TCF4 overexpression virus significantly repressed the increase of Na1.8 and prevented the development of hyperalgesia in rats. Moreover, we confirmed the efficient role of an overexpressed TCF4 in preventing the CFA- and SNI-induced neuronal hyperexcitability by calcium imaging. Our results suggest that attenuating the dysregulation of Na1.8 by targeting TCF4 may be a novel therapeutic strategy for chronic inflammatory and neuropathic pain.

Gamma-amino butyric acid (GABA) is an inhibitory neurotransmitter in the mature brain, but is excitatory during development and after motor nerve injury. This difference in GABAergic action depends on the intracellular chloride ion concentration ([Cl]), primarily regulated by potassium chloride co-transporter 2 (KCC2). To reveal precise processes of the neuropathic pain through changes in GABAergic action, we prepared tibial nerve ligation and severance models using male mice, and examined temporal relationships amongst changes in (1) the mechanical withdrawal threshold in the sural nerve area, (2) localization of the molecules involved in GABAergic transmission and its upstream signaling in the dorsal horn, and (3) histology of the tibial nerve. In the ligation model, tibial nerve degeneration disappeared by day 56, but mechanical allodynia, reduced KCC2 localization, and increased microglia density remained until day 90. Microglia density was higher in the tibial zone than the sural zone before day 21, but this result was inverted after day 28. In contrast, in the severance model, all above changes were detected until day 28, but were simultaneously and significantly recovered by day 90. These results suggested that in male mice, allodynia may be caused by reduced GABAergic synaptic inhibition, resulting from elevated [Cl] after the reduction of KCC2 by activated microglia. Furthermore, our results suggested that factors from degenerating nerve terminals may diffuse into the sural zone, whereby they induced the development of allodynia in the sural nerve area, while other factors in the sural zone may mediate persistent allodynia through the same pathway.

Patients with rheumatoid arthritis (RA) often receive opioid analgesics for pain management. We examined the association between mental health conditions and the risk of chronic opioid therapy.

Various conservative treatments and surgical techniques have been reported in the literature as efficient and feasible measures to treat the cubital tunnel syndrome. However, there has been no consensus on the best management of the syndrome, and uniform standardised guidelines have not yet been accepted or introduced. With our study, we present our experience on the clinical efficacies and outcomes of the surgical techniques of neurolysis alone and neurolysis associated with ulnar nerve anterior transposition at the elbow joint in patients with neuropathic symptoms due to cubital tunnel syndrome.

Diabetes mellitus (DM) was reported as one of the most common non-communicable diseases during Hajj. However, few studies evaluated acute complications of DM during Hajj. Therefore, this study aims to explore the most common acute complications among pilgrims with DM during Hajj 2017 and its clinical presentations.

The original publication listed author Alan Kaye as "A. Kaye," but his name should read "A.D. Kaye." The correct author name is presented in this article.

Non-union is a regular complication of arthrodeses. Standard treatment includes revision surgery with frequent need for re-revision due to persistent non-union. Particularly patients with concomitant diseases are at risk of secondary complications. There is a need for evaluation of alternative treatment options. The aim of this study is to provide first evidence on union-rate and pain course after focussed extracorporeal shock-wave therapy of arthrodesis non-unions.

To evaluate the effects of transcutaneous electrical nerve stimulation (TENS) compared to placebo TENS and a control group on pain, pulmonary function, respiratory muscle strength, and analgesic medications in the postoperative period of thoracotomy in an Intensive care unit (ICU).

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting primarily joints and an increased risk of developing malignant lymphomas in RA has been well reported. However, primary lymphoma in a joint in RA patient is rare. We report the case of a 65-year-old man with RA suffering from pain and swelling of left sternoclavicular (SC) joint, which was not relieved by adding low-dose glucocorticoid. Magnetic resonance imaging (MRI) showed a para-osseous soft tissue swelling around the SC joint and a fracture of proximal clavicle. Histology of the soft tissue demonstrated diffuse large B-cell lymphoma and the patient subsequently underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. He was successfully treated with six cycles of R-CHOP chemotherapy, with discontinuation of MTX, resulting in a complete response. We performed a literature review and identified nine cases of lymphoma which involved joints in patients with rheumatoid arthritis. This is the first described case of a primary large B-cell lymphoma involving the unilateral SC joint in a patient with RA, which was initially confused with aggravation of RA. Therefore, malignant lymphoma should be considered in the differential diagnosis when a RA patient develops monoarthritis with spontaneous fracture, even without B symptoms.