Rejected

Calcium pyrophosphate deposition (CPPD) can be induced by a persistent hypomagnesemia. Tacrolimus is an immunosuppressive treatment especially used in organ transplant, potentially inducer of hypomagnesemia by renal loss. A 53-year-old man, liver transplant 10 months earlier, developed an acute peripheral oligoarthritis of wrist, hip and elbow with fever, associated with acute low back pain. Synovial fluid was sterile, and revealed calcium pyrophosphate crystals. Spinal imaging showed inflammatory changes. Magnesium blood level was low at 0.51 mmol/l, with high fractional excretion in favor of renal loss. Tacrolimus was changed for everolimus, proton pump inhibitor was stopped, and magnesium oral supplementation was started. After 8 months follow-up and slow prednisone tapering, he did not relapse pain. Persistent hypomagnesemia is a rare secondary cause of CPPD. In this entity, drug liability should be investigated such as tacrolimus in organ transplant patient.

Chronic venous insufficiency is found to some extent in a large proportion of the world's population, especially in the elderly and obese. Despite its prevalence, little research has been pursued into this pathology when compared to similarly common conditions. Pain is often the presenting symptom of chronic venous insufficiency and has significant deleterious effects on quality of life. This manuscript will describe the development of pain in chronic venous insufficiency, and will also review both traditional methods of pain management and novel advances in both medical and surgical therapy for this disease.

The potential adverse impact of inhalational anesthetics on the developing brain was highlighted by the addition of a medication warning by the U.S. Food and Drug Administration for their use in the pediatric population. To investigate mechanisms by which early life anesthesia exposure could induce long-term neuronal dysfunction, we exposed rats to 1 minimum alveolar concentration sevoflurane at 7 days of life. The animals were raised normally until adulthood (P300) prior to sacrifice and analysis of cortical tissue structure (TEM), mitochondrial quality control and biogenesis pathways (Western blot, ELISA, ADP/ATP content), and markers of oxidative stress, proteotoxicity and inflammation (Western blot, ELISA). We found that early life anesthesia exposure led to adverse changes in mitochondrial quality maintenance pathways, autophagy and mitochondrial biogenesis. Although there was an escalation of oxidative stress markers and an increase in the nuclear localization of stress-related transcription factors, cellular redox compensatory responses were blunted, and oxidative phosphorylation was reduced. We found upregulation of mitochondrial stress and proteotoxicity markers, but a significant reduction of mitochondrial unfolded protein response end-effectors, contributing to an increase in inflammation. Contrary to acute exposure, we did not find an increase in apoptosis. Our findings suggest that a limited, early exposure to anesthesia may produce lasting cellular dysfunction through the induction of a sustained energy deficient state, resulting in persistent neuroinflammation and altered proteostasis/toxicity, mimicking aspects of chronic neurodegenerative diseases.

Endometriosis is associated with various types of intense pain. In addition to nociceptive pain, there is also a nociplastic reaction with central sensitization. Atypical symptoms such as acyclic lower abdominal pain, radiating pain, non-specific bladder and intestinal complaints or even depression are frequent as are classic cyclical complaints such as severe dysmenorrhea, cyclical lower abdominal pain, dyspareunia, dysuria and dyschezia. In cases of a diverse range of symptoms, patients often consult not just gynecologists but specialists from other disciplines (e.g., internal medicine, gastroenterology, orthopedics, pain therapy, psychology).

The periosteal and endosteal surfaces of mature bone are densely innervated by sensory nerves expressing TrkA, the high-affinity receptor for nerve growth factor (NGF). In previous work, we demonstrated that administration of exogenous NGF significantly increased load-induced bone formation through the activation of Wnt signaling. However, the translational potential of NGF is limited by the induction of substantial mechanical and thermal hyperalgesia in mice and humans. Here, we tested the effect of gambogic amide (GA), a recently identified robust small molecule agonist for TrkA, on hyperalgesia and load-induced bone formation. Behavioral analysis was used to assess pain up to one week after axial forelimb compression. Contrary to our expectations, GA treatment was not associated with diminished use of the loaded forelimb or sensitivity to thermal stimulus. Furthermore, dynamic histomorphometry revealed a significant increase in relative periosteal bone formation rate as compared to vehicle treatment. Additionally, we found that GA treatment was associated with an increase in the number of osteoblasts per bone surface in loaded limbs as well as a significant increase in the fold change of Ngf, Wnt7b, and Axin2 mRNA expression as compared to vehicle (control). To test the effect of GA on osteoblasts directly, we cultured MC3T3-E1 cells for up to 21 days in osteogenic differentiation media containing NGF, GA, or vehicle (control). Media containing GA induced the significant upregulation of the osteoblastic differentiation markers Runx2, Bglap2, and Sp7 in a dose-dependent manner, whereas treatment with NGF was not associated with any significant increases in these markers. Furthermore, consistent with our in vivo findings, we observed that administration of 50 nM of GA upregulated expression of Ngf at both Day 3 and Day 7. However, cells treated with the highest dose of GA (500 nM) had significantly increased apoptosis and impaired cell proliferation. In conclusion, our study indicates GA may be useful for augmenting skeletal adaptation to mechanical forces without inducing hyperalgesia.

To assess the effectiveness of a nonopioid pain regimen in controlling postoperative pain as compared to a traditional opioid pain control following primary meniscectomy or meniscal repair.

The prediction of patient responses to potentially painful stimuli remains a challenge in PICUs. We investigated the ability of the paintracker analgesia monitor (Dolosys GmbH, Berlin, Germany) measuring the nociceptive flexion reflex threshold, the cerebral sedation monitor bispectral index (Medtronic, Dublin, Ireland), the COMFORT Behavior, and the modified Face, Legs, Activity, Cry, Consolability Scale scores to predict patient responses following a noxious stimulus.

Migraine headache is a common, debilitating condition responsible for astronomical societal burden. The chronicity of migraine headaches necessitates the use of many healthcare services. Preventative treatment remains the desirable option for this patient population. Pharmacologic advances have led to the development of erenumab, a monoclonal antibody calcitonin gene-related peptide receptor antagonist that directly interferes with the known biochemical pathway of migraine initiation. Alternatively, surgical decompression of migraine trigger sites is a historically effective preventative option for certain patients experiencing migraine headaches. As new treatments emerge, the large economic burden of migraine headaches requires cost evaluation against already available preventative modalities.

We summarize a case of transient oculomotor nerve palsy in a pregnant woman with a cavernous sinus meningioma. When pregnant women present with acute ophthalmic signs and symptoms, meningioma should be considered during diagnostic workup given the common proximity of growing meningiomas to visual pathways and ocular motor nerves within the parasellar region.