Rejected

The aim of the present study was to determine the involvement of the VTA 5-HT receptors in analgesia induced by the co-administration of morphine and dextromethorphan (DM). Male Wistar rats were bilaterally cannulated in the VTA by the stereotaxic instrument. The tail-flick and formalin tests were performed to assess nociception in the acute and tonic pain conditions respectively. The present data indicated that intraperitoneal (i.p.) administration of morphine increased the tail-flick latency (1-4 mg/kg) and decreased the pain score of formalin test (2-8 mg/kg), showing an analgesic effect. Co-administration of ineffective doses of morphine (1 or 2 mg/kg) with DM (30 mg/kg, i.p.) induced analgesia in both animal models. Interestingly, intra-VTA microinjection of 5HT receptors antagonist, S-WAY100-135 (0.5 and 1 µg/kg), inhibited the analgesic effect of morphine plus DM in both acute and tonic pain models. It should be considered that the same doses of DM or S-WAY100-135 by itself had no effects on antinociception in the animal models. Overall, these results indicated that systemic blockade of NMDA receptors via DM administration potentiated the response of a low dose of morphine to induce analgesic effect. Additionally, it seems that the VTA serotonergic system via 5HT receptors mediates the potentiative effect of DM on morphine-induced analgesia.

MINI: In a cross-sectional cohort study comparing MRI phenotypes for chronic low back pain between PATIENT.: subjects and asymptomatic-subjects, we uncovered an association between endplate damage and adjacent paraspinal muscle quality that is predictive of symptoms for chronic low back pain.

MINI: Poor self-image and mental health as well as large postural changes of apical vertebral translation at main thoracic curve were associated with chronic back pain or back pain at rest in AIS patients. Psychological factors and postural changes of spinal alignment rather than curve severity were associated with back pain.

A new set of 5-chlorobenzoxazole- and 5-chlorobenzothiazole-based derivatives containing the azepane ring as a basic moiety was designed, synthesized and evaluated through binding assays to measure their affinity and selectivity towards σ and σ receptors. Compounds 19, 22 and 24, with a four units spacer between the bicyclic scaffold and the azepane ring, showed nanomolar affinity towards both receptor subtype and the best K values (K σ = 1.27, 2.30, and 0.78 and K σ = 7.9, 3.8, and 7.61 nM, respectively). Evaluation of cytotoxic and apoptotic effects in MCF-7 human cancer cells was useful to assess σ receptor activity, while an in vivo mice model of inflammatory pain allowed to analyze σ receptor pharmacological properties. In vitro and in vivo results suggested that compound 19 is a σ/σ agonist, compound 24 a σ antagonist/σ agonist, whereas compound 22 might act as σ antagonist/σ partial agonist. Due to their pharmacological profile, a potential therapeutic application in cancer of aforesaid novel σ/σ receptor ligands, especially 22 and 24, is proposed.

Autoimmune diseases including inflammatory bowel disease (IBD) occur in association with myelodysplastic syndrome (MDS). MDS-associated IBD frequently demonstrates a complicated course. We herein report the first case with MDS-associated IBD that was successfully treated with ustekinumab (UST), an anti-interleukin (IL) 12/23p40 monoclonal antibody. A 63-year-old man with a 7-year history of MDS was referred for examination of diarrhea, abdominal pain and fever. A blood examination revealed a marked elevation of C-reactive protein. Colonoscopy showed multiple ulcers in the terminal ileum. He was resistant to anti-TNF-α antibody and azacitidine. Subsequently, UST treatment reduced colonic IL-17 and IL-6 expression and the patient currently maintains a state of remission.

Ethnopharmacological knowledge is important for the identification of active compounds from natural products. Pain may have different aetiologies with complex mechanisms. Tabernaemontana catharinensis is well known for indole alkaloids, being used empirically in folk medicine, with antimicrobial and anti-inflammatory as well as antiofidic actions among others.

Shingles and its most common disabling complication, post-herpetic neuralgia (PHN), represents a serious public health challenge in the older population. The decline in the T-cell-mediated immune response to Varicella Zoster Virus after age 50 is clearly associated with increased risk of viral reactivation, causing an acutely painful zoster rash which may have a severe prodrome of dermatomal pain and persist as seriously debilitating PHN well beyond the resolution of the rash. However, new vaccines and adjuvants are being developed and trialed, and are now more effective in preventing shingles and the sequelae of PHN. Those vaccines that possess the ability to enhance antigen presentation and reverse memory T cell exhaustion, as well as diminish the immune suppressive effects of regulatory T cells, are most likely to be effective in older adults.

Gamma Knife radiosurgery (GKRS) is a noninvasive surgical treatment option for patients with medically refractive classic trigeminal neuralgia (TN). The long-term microstructural consequences of radiosurgery and their association with pain relief remain unclear. To better understand this topic, the authors used diffusion tensor imaging (DTI) to characterize the effects of GKRS on trigeminal nerve microstructure over multiple posttreatment time points.

Fifty-five year-old female presented with five weeks of progressively worsening headaches precipitated by a sudden neck movement. The headaches were exacerbated by sitting up or standing. There was associated diplopia and facial pain. Investigations were consistent with intracranial hypotension with a possible spontaneous spinal cerebrospinal fluid leak. Symptoms improved dramatically after an epidural blood patch.