Rejected

Male, 68 years old, suffering from prurigo nodularis for 7 months, and did not show any significant improvement after oral and topical medications. After 4 months of acupuncture treatment, the NRS for itch scores decreased from 9 to 1; the NRS for sleep scores increased from 5 to 9; HADS decreased from 14 to 2; DLQI decreased from 9 to 5; IGA decreased from 4 to 3. After a 2-month follow-up, the patient was stable in all aspects without new rash.

Previous studies have identified altered brain changes in chronic pain patients, however, it remains unclear whether these changes are reversible. We summarized the neural and molecular changes in patients with chronic pain and employed a meta-analysis approach to quantify the changes. We included 75 studies and 11 of these 75 studies were included in the activation likelihood estimation (ALE) analysis. In the 62 functional magnetic resonance imaging (fMRI) studies, the primary somatosensory and motor cortex (SI and MI), thalamus, insula, and anterior cingulate cortex (ACC) showed significantly decreased activity after the treatments compared to baseline. In the 13 positron emission tomography (PET) studies, the SI, MI, thalamus, and insula showed significantly increased glucose uptake, blood flow, and opioid-receptor binding potentials after the treatments compared to baseline. A meta-analysis of fMRI studies in patients with chronic pain, during pain-related tasks, showed a significant deactivation likelihood cluster in the left medial posterior thalamus. Further studies are warranted to understand brain reorganization in patients with chronic pain compared to the normal state, in terms of its relationship with symptom reduction and baseline conditions.

The aim of this study will be to investigate the therapeutic effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) along with symptomatic slow-acting drugs for the treatment of osteoarthritis (SYSADOA), JOINS tablets, for degenerative knee osteoarthritis (OA) treatment and to determine the analgesic and anti-inflammatory effects of the combination therapy. In addition, we will investigate whether JOINS treatment alone after NSAID and JOINS combination treatment is effective in relieving and maintaining knee OA symptoms.

is used traditionally to treat pain. The antinociceptive properties of the hydroethanolic leaf extract of (PLE) were evaluated in rats and mice. Mice were pretreated orally with PLE (30, 100, and 300 mg kg) and evaluated for antinociceptive effects in the acetic acid-, glutamate-, and formalin-induced nociception models. Additionally, mechanical hyperalgesia models were used to evaluate PLE's influence on TNF– and IL-1-induced hyperalgesia in rats. In the acetic acid-induced nociception model, 100 mg kg PLE exhibited the highest antinociceptive activity of 95.13 ± 9.52% at < 0.0001, followed by the 300 mg kg (85.44 ± 5.75%; < 0.0001) and then the 30 mg kg (67.95 ± 18.55%; < 0.01), compared to morphine 3 mg kg i.p. (86.97 ± 9.52; < 0.0001). PLE (30, 100, and 300 mg kg) also showed significant ( < 0.05) antinociceptive effect in phase two of the formalin-induced nociception with % inhibitions of 66.88 ± 12.17, 75.12 ± 9.01, and 89.12 ± 4.32%, respectively, compared to 3 mg/kg morphine (97.09 ± 2.84%). Similarly, PLE (30, 100, and 300 mg kg) significantly reduced pain in the glutamate-induced nociception model with % inhibitions of 79.28 ± 8.17, 90.54 ± 5.64, and 96.49 ± 1.43%, respectively, whereas ketamine (5 mg/kg i.p.) reduced nociception to be 59.94 ± 18.14%. All doses of PLE significantly reduced nociceptive scores in TNF– and IL-1-induced mechanical hyperalgesia ( < 0.01). Similarly, PLE significantly inhibited bradykinin-induced nociception. The hydroethanolic extract of has antinociceptive effects; this is the first scientific report providing evidence to validate its traditional use for the management of pain.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are widely used globally for the treatment of pain and inflammation, and in the case of aspirin, for secondary prevention of cardiovascular disease. Chronic non-steroidal anti-inflammatory drug use is associated with potentially serious upper gastrointestinal adverse drug reactions (ADRs) including peptic ulcer disease and gastrointestinal bleeding. A few clinical and genetic predisposing factors have been identified; however, genetic data are contradictory. Further research is needed to identify clinically relevant genetic and non-genetic markers predisposing to NSAID-induced peptic ulceration.

Osteoarthritis and other degenerative joint diseases are common causes of chronic pain in cats. Frunevetmab is a felinized monoclonal antibody that binds to nerve growth factor (NGF) and provides relief from pain by blocking the receptor-mediated signaling cascade induced by NGF. Results from three studies were combined to provide an overview of frunevetmab pharmacokinetics (PK) and immunogenicity. The objective of the first study was to establish the pharmacokinetic parameters resulting from intravenous (IV) and subcutaneous (SC) administration of frunevetmab to the feline patient population at 3 mg/kg. Ten adult cats with naturally-occurring osteoarthritis were administered frunevetmab in a crossover design at 28 day intervals. Non-compartmental pharmacokinetic analysis of the plasma concentration-time data showed that the half-life was 10.1 ± 1.9 days after IV dosing and the SC bioavailability was 60.3 ± 15.8% with maximum drug levels observed at 3-7 days after dosing. Plasma samples were collected at ~28 days after dosing during two field safety and effectiveness studies of cats with degenerative joint disease. The doses ranged from 1.0 to 2.8 mg/kg; 2 or 3 doses were administered either SC/IV, SC/SC, or SC/SC/SC. The data from these studies along with the data from the laboratory pharmacokinetic study were analyzed using non-linear mixed-effects (NLME) modeling. The model closely predicted the trough concentrations from the two field studies, including the IV treatment in the pilot field study. The trough concentrations were predicted to be close to steady-state after 2 doses. A second objective was to determine the incidence and clinical relevance of frunevetmab immunogenicity. A three-tier anti-drug antibody assay (screen, confirm, titer) was developed and validated. Immunogenicity was assessed in 259 frunevetmab-treated animals enrolled in the two field studies. Only 4 of these animals (1.5%) appeared to develop immunogenicity to frunevetmab. None of the four exhibited adverse events attributed to immunogenicity and no impact on drug levels or efficacy was observed in three of the animals. In the placebo animals, 2.3% (3/131) appeared to develop treatment-emergent immunogenicity. Overall, frunevetmab administration resulted in a very low incidence of treatment-emergent immunogenicity with no safety findings and minimal effect on drug exposure and efficacy.

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.