Rejected

Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT receptor (5-HTR) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HTR could influence phosphorylation of protein kinase A (PKA)- or extracellular signal-regulated kinase (ERK)-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HTR in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 min every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HTR antagonist (SB269970) or 5-HTR agonist (AS19) was administered intrathecally before each IS application at 2-day intervals during the 7-day injection protocol. The changes in 5-HTR and 5-HTR-associated signaling pathway were examined by real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) analyses. When compared with IS group, mechanical and thermal pain thresholds of the IS + EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HTR mRNA expression and protein levels were detected in the IS + EA group. More importantly, 5-HTR agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK. Injecting 5-HTR antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK. Our findings indicate that 5-HTR mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK in TG and TNC.

Depression and anxiety are common among patients with migraine and usually associated with a humanistic and financial burden. This study aims to examine the direct healthcare expenditures among adults with migraine alone or with comorbid anxiety and/or depression. This was a retrospective cross-sectional study using 2012, 2014, and 2016 Medical Expenditure Panel Survey data. Adult patients aged ≥22 years with migraine headache were included in the study. The direct healthcare expenditures of four migraine groups (migraine alone, migraine and anxiety, migraine and depression, and migraine and both conditions) were compared. There were 1,556 patients who met the inclusion criteria and eventually enrolled in the study. Approximately 42% of the study sample had migraine with comorbid depression and/or anxiety (16.1% have depression, 12.3% have anxiety disorder, and 13.9% have both). The mean total healthcare expenditures of adults with migraine alone ($6,461) were significantly lower than those with comorbid depression and anxiety ($11,102), comorbid anxiety ($10,817), and comorbid depression ($14,577). Migraine with comorbid anxiety and depression was significantly associated with incremental costs of $1,027 in outpatient and $662 emergency room healthcare expenditures and prescription drug compared to the migraine alone group. The healthcare expenditures associated with migraine with comorbid depression and/or anxiety are significantly higher than those without mental health comorbidities. Therefore, regular depression and anxiety screening for patients with migraine may help reduce the healthcare expenditures associated with depression and/or anxiety comorbidities and improve the quality of care.

There is a critical need for non-narcotic analgesic adjuncts in the treatment of thoracic pain. We evaluated the efficacy of intercostal cryoneurolysis as an analgesic adjunct for chest wall pain, specifically addressing the applicability of intercostal cryoneurolysis for pain control after chest wall trauma.

This study aimed to assess subjective sleep and wake disorders (SWD) in patients with osteoarthritis and comorbid end-stage renal disease (ESRD) receiving hemodialysis (ESRD-HD) compared to patients with osteoarthritis and without chronic kidney disease (CKD) as well as to clarify of the association of subjective sleep characteristics with the levels of anxiety and depression and pain, general health score and laboratory parameters in these cohorts.

Psychiatric disorders are frequently encountered in many neurological disorders, such as Alzheimer's and Parkinson diseases along with epilepsy, migraine, essential tremors, and stroke. The most common comorbid diagnoses in neurological diseases are depression and anxiety disorders along with cognitive impairment. Whether the underlying reason is due to common neurochemical mechanisms or loss of previous functioning level, comorbidities are often overlooked. Various treatment options are available, such as pharmacological treatments, cognitive-behavioral therapy, somatic interventions, or electroconvulsive therapy. However oral antidepressant therapy may have some disadvantages, such as interaction with other medications, low tolerability due to side effects, and low efficiency. Natural compounds of plant origin are extensively researched to find a better and safer alternative treatment. Experimental studies have shown that phytochemicals such as alkaloids, terpenes, flavonoids, phenolic acids as well as lipids have significant potential in and models of psychiatric disorders. In this review, various efficacy of natural products in and studies on neuroprotective and their roles in psychiatric disorders are examined and their neuro-therapeutic potentials are shed light.

Pain and depression are leading causes of disability and of profound social and economic burden. Their impact is aggravated by their chronicity and comorbidity and the insufficient efficacy of current treatments. Morphological and functional metabolism studies link chronic pain and depressive disorders to dysfunctional neuroplastic changes in fronto-limbic brain regions that control emotional responses to painful injuries and stressful events. Glutamate modulators are emerging new therapies targeting dysfunctional brain areas implicated in the generation and maintenance of chronic pain and depression. Here, we report the effects of two clinically approved glutamate modulators: acetyl-L-carnitine (ALCAR) and S, R(±)ketamine (KET). ALCAR is a natural neurotrophic compound currently marketed for the treatment of neuropathies. KET is the prototypical non-competitive antagonist at -methyl-D-aspartate glutamate receptors and a clinically approved anesthetic. Although they differ in pharmacological profiles, ALCAR and KET both modulate aminergic and glutamatergic neurotransmissions and pain and mood. We assessed in rats the effects of ALCAR and KET on cerebral metabolic rates for glucose (rCMRglc) and assessed clinically the effects of ALCAR in chronic pain and of KET in post-operative pain. ALCAR and KET increased rCMRglc at similar degrees in prefrontal, somatosensory, and cingulate cortices, and KET increased rCMRglc at a different, much larger, degree in limbic and dopaminergic areas. While rCMRglc increases in prefrontal cortical areas have been associated with analgesic and antidepressant effects of ALCAR and KET, the marked metabolic increases KET induces in limbic and dopaminergic areas have been related to its psychotomimetic and abuse properties. In patients with chronic neuropathic pain, ALCAR (1,000 mg/day) yielded to a fast (2 weeks) improvement of mood and then of pain and quality of life. In day-surgery patients, KET improved dischargeability and satisfaction. In obese patients undergoing bariatric surgery, a single, low dose of KET (0.5 mg/kg) at induction of anesthesia determined a very fast (hours) amelioration of post-operative depression and pain and an opioid-sparing effect. These findings indicate that ALCAR and KET, two non-selective glutamate modulators, still offer viable therapeutic options in comorbid pain and depression.

Local disturbances of the microbiota are common in dogs with underlying skin conditions. Antiseptic topical products are indicated to control such superficial disorders. The objective of this study was to evaluate the performance of a daily application of pads containing Ophytrium and chlorhexidine digluconate 3% (DOUXO® S3 PYO Pads, Ceva Santé Animale, France) in dogs with focal bacterial and/or overgrowth. Eighteen dogs with focal skin dysbiosis were included in the analysis of this prospective, multicentric, field study. Dogs received daily pad applications for 14 days. Bacterial and/or counts per microscopic field and a global score of the most affected patch (0-17 scale based on extension, severity, bacterial, and cytological scores) were assessed by a veterinarian and pruritus by the owner (Pruritus Visual Analog Scale) on days (D)0, D7, D14. Owner and veterinarian evaluations for performance and satisfaction were recorded. Eleven dogs had primarily cocci overgrowth and seven mostly . Mean bacterial and counts decreased after 14 days (6.9-1.1; 7.6-1.5, respectively); 88.9% of dogs achieved a ≥70% microbial decrease and had ≤2 bacteria and ≤1 per oil field. Mean global score of the most affected patch and pruritus score significantly improved at D14, respectively, from 8.6 to 2.6 and 4.5 to 1.2 ( < 0.05 each, mean improvements of 70.4 and 71.4%, respectively). Global veterinary assessment of the protocol was satisfactory, good, or excellent in 88.9% of cases. Most owners (94.4%) considered the protocol efficacious. Using a pad containing Ophytrium and chlorhexidine digluconate 3% daily for 14 days improved the skin condition and pruritus of dogs with local dysbiosis, resulting in high satisfaction levels for both veterinarians and dog owners.

This research was designed to probe into the effect of multimodal analgesia on gynecological cancer patients after radical resection.

A 52-year-old African-American male patient with end-stage renal disease due to hypertension underwent deceased donor kidney transplant procedure with no immediate complications. The postprocedure complications, interventions, and course were abstracted by chart review. The ureteric stent was removed with flexible cystoscopy on postoperative day (POD) 24. 24 hours later, the patient presented with abdominal pain and inability to urinate. An urgent ultrasound and noncontrast CT scan showed grade 4 hydronephrosis of the transplanted kidney. A percutaneous nephrostomy stent was placed for urinary diversion. A large ureteric hematoma filling the lumen of the mid to distal ureter was identified on the nephrostogram and was evacuated. A follow-up nephrostogram on POD 44 revealed a distal ureter stricture and persistent well-formed midureter filling defect. A repeat nephrostogram performed at POD 72 was done with stricture dilatation, internalization of stents, and removal of a percutaneous nephrostomy tube. The patient was maintained on antibiotics for UTI prophylaxis throughout the course.

Preliminary investigations showed that preparations from Arabian Gulf catfish (, Val) epidermal gel secretion (PCEGS) exhibit potent anti-inflammatory and healing properties as shown in our previous clinical trials for the healing of non-healing diabetic foot ulcers, chronic back pain, and some other neurological disorders. Here, we report for the first time a unique preparation containing only proteins and lipids (soluble protein fraction B, SPF-FB), derived from the PCEGS accelerated the healing and recovery of sensory-motor functions of experimental sciatic nerve crush injury in rats with its unique neuroprotective and neuroregenerative properties on the spinal neurons and peripheral nerve fibers. Male rats were randomly assigned to five groups: (I) NAÏVE, (II) SHAM, (III) CRUSH treated with saline, (IV) CRUSH + SPF-FB treated with 3 mg/kg intraperitoneally (IP) and (V) CRUSH + SPF-FB treated with 6 mg/kg subcutaneously (SC) groups. The crush groups III, IV and V underwent sciatic nerve crush injury, followed by treatment daily for 14 days with saline, SPF-FB IP and SPF-FB SC. All animals were tested for the neurobehavioral parameters throughout the 6 weeks of the study. Sciatic nerve and spinal cord tissues were processed for light and electron histological examinations, stereological analysis, immunohistochemical and biochemical examinations at Week 4 and Week 6 post-injury. Administration of SPF-FB IP or SC significantly enhanced the neurobehavioral sensory and motor performance and histomorphological neuroregeneration of the sciatic nerve-injured rats. The stereological evaluation of the axon area, average axon perimeters, and myelin thickness revealed significant histomorphological evidence of neuroregeneration in the FB-treated sciatic nerve crush injured groups compared to controls at 4 and 6 weeks. SPF-FB treatment significantly prevented the increased in NeuN-immunoreactive neurons, increased GFAP immunoreactive astrocytes, and decreased GAP-43. We conclude that SPF-FB treatment lessens neurobehavioral deficits, enhances axonal regeneration following nerve injury. We conclude that SPF-FB treatment lessens neurobehavioral deficits and enhances axonal regeneration following nerve injury, as well as protects spinal neurons and enhances subcellular recovery by increasing astrocytic activity and decreasing GAP-43 expression.