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ies, ranging from +5.9% (99% confidence interval 4.8%-7.0%) to +39.8% (99% confidence interval 38.3%-41.5%) in people on the highest daily pregabalin dose. Among people using both pregabalin and benzodiazepines, the dose remained constant over time for people in all trajectories. Notwithstanding its reputation as opioid-sparing, in this outpatient setting, we observed that people using opioids tended to use higher opioid daily doses after pregabalin initiation, especially those on high pregabalin doses.

The number of placebo surgical trials on musculoskeletal conditions is increasing, but little is known about the quality of their design and methods. This review aimed to (1) assess the level of placebo fidelity (ie, degree to which the placebo control mimicked the index procedure) in placebo trials of musculoskeletal surgery, (2) describe the trials' methodological features using the adapted Applying Surgical Placebo in Randomised Evaluations (ASPIRE) checklist, and (3) describe each trial's characteristics. We searched 4 electronic databases from inception until February 18, 2021, for randomised trials of surgery that included a placebo control for any musculoskeletal condition. Protocols and full text were used to assess placebo fidelity (categorised as minimal, low, or high fidelity). The adapted 26-item ASPIRE checklist was also completed on each trial. PROSPERO registration number CRD42021202131. A total of 30,697 studies were identified in the search, and 22 placebo-controlled surgical trials of 2045e "conduct" (13%) and "interpretation and translation" (11%) of the placebo trials. Most trials sufficiently reported their rationale and ethics, but interpretation and translation are areas for improvement, including greater stakeholder involvement. Most trials used a high-fidelity placebo procedure suggesting an emphasis on blinding and controlling for nonspecific effects.

Altered brain structure and function is evident in adults with multisite chronic pain. Although many such adults trace their pain back to childhood, it has been difficult to disentangle whether central nervous system alterations precede or are consequences of chronic pain. If the former is true, aberrant brain activity may identify children vulnerable to developing chronic pain later in life. We examined structural and functional brain magnetic resonance imaging metrics in a subset of children from the first two assessments of the Adolescent Brain and Cognitive Development (ABCD) Study. Children (ages 9-10) who were pain-free at baseline and then developed multisite pain one year later (n=115) were matched to control children who were pain-free at both timepoints (n=230). We analyzed brain structure (cortical thickness and gray matter volume) and function (spontaneous neural activity and functional connectivity). Results were deemed significant at the cluster level p < 0.05 false discovery rate correctedork, somatosensory and default mode network regions. No significant differences in brain structure were observed. Increased neural activity and functional connectivity between brain regions, consistent to that seen in adults with chronic pain, exist in children prior to developing multisite pain. These findings may represent a neural vulnerability to developing future chronic pain.

Neuropathy is common among individuals with diabetes mellitus, and is associated with decreased quality of life, greater comorbidity, and substantial economic burden. However, the mechanisms underlying painful diabetic polyneuropathy has yet to be fully elucidated. While it is recognized that diabetic polyneuropathy places patients at a greater risk for developing neuropathic pain, it is still not clear why some individuals develop pain and others do not. Similar to other chronic pain conditions, painful diabetic neuropathy is likely driven by alterations in both the peripheral and central nervous system. Experimental conditioned pain modulation paradigms have contributed substantially to our current understanding of chronic pain across various disease states. In a new study, researchers have extended this work by examining the efficiency of conditioned pain modulation in patients with painful and non-painful diabetic polyneuropathy. Surprisingly, the results indicate individuals with painful neuropathy expstanding of chronic pain across various disease states. In a new study, researchers have extended this work by examining the efficiency of conditioned pain modulation in patients with painful and non-painful diabetic polyneuropathy. Surprisingly, the results indicate individuals with painful neuropathy experience greater endogenous pain inhibition, which may seem counterintuitive at first blush. Here, we discuss potential explanations and directions for future research, including consideration for age effects, testing site, and disease type, with the goal of further advancing this important line of research.

Prolotherapy is widely used in pain control and tissue repair in pain medicine. The classical mode is injection with hypertonic dextrose in muscle or perimysium. However, the analgesic mechanism is still not known. Here we successfully established dextrose-mediated antinociception in a mouse model of fibromyalgia. The antinociceptive effects of dextrose injections were evaluated in a mouse model of fibromyalgia, in which bilateral chronic mechanical hyperalgesia was induced by unilateral intramuscular acid injection. The injectant (dextrose), dose (≥ 5%) and volume (>10 μL) but not osmolarity were essential for the prolotherapy. Further studies showed that activation of acid-sensing ion channel 1a (ASIC1a), neural activation, and the release of substance P from muscle afferents were required in the dextrose-induced reduction of mechanical hypersensitivity. Both pharmacological blockade and genetic deletion of ASIC1a or substance P as well as lidocaine abolished the dextrose-induced antinociception in micbstance P as well as lidocaine abolished the dextrose-induced antinociception in mice with chronic hyperalgesia. Moreover, intramuscular dextrose injection induced phosphorylated extracellular signal-regulated kinase (pERK) expression in dorsal root ganglia neurons expressing substance P; the pERK expression was inhibited by the ASIC1a antagonist PcTx1. The optimal settings for prolotherapy in fibromyalgia-like pain are dextrose- and volume-dependent, and the peripheral antinociception involves ASIC1a and substance P signaling in muscle afferents. This study suggests a possible mechanism of action of dextrose prolotherapy in non-inflammatory muscle pain such as fibromyalgia and provides insights for treating other types of chronic pain.

Pathophysiological causes of low back pain (LBP) remain generally unclear, so focus has shifted to psychosocial features and central pain processing. Effects of attentional and affective manipulation on conditioned pain modulation (CPM) and tonic pain perception were examined in thirty recurrent LBP patients in two sessions, one with and one without clinical pain, and compared to healthy participants. Phasic cuff pressure on one leg, scored on a numerical rating scale (NRS), was used for test-stimuli (TS) and contralateral tonic cuff pain rated on an electronic visual analogue scale (eVAS) was the conditioning-stimulus (CS). TS were assessed before and during 1) control with no manipulation/CS, 2) three attentional manipulations (Flanker with/without CS or CS-Only), and 3) three affective manipulations (positive, neutral, negative pictures) with CS. Greater inhibition of TS-NRS scores was observed in CS-only (P=0.028), combined CS&attention (P=0.026), and CS&Positive (P=0.006) than Control paradigmshe CS-Only paradigm than all others (P less then 0.02) and lower facilitation was additionally observed in the CS&Positive paradigm compared to CS&Attention and CS&Negative paradigms (P less then 0.01). Flanker effects and interruptive effects of CS pain on attention were observed consistent with prior findings, and affective manipulation produced less shift in valence among people with RLBP than controls (P less then 0.05). Attention and positive affect with CS pain evoked CPM, and all attentional/affective tasks, especially positive affect, reduced facilitation of CS pain.Addison disease is rare, and it is rarer to coexist with systemic lupus erythematosus and antiphospholipid antibody syndrome. We hereby reported a middle-aged female who presented with nausea, vomit, skin and mucosa hyperpigmentation, hypotension, hyponatremia, and pulmonary infection after diagnosis of deep venous thrombosis of the left lower extremity and systemic lupus erythematosus in 2012. The patient was finally diagnosed with antiphospholipid antibody syndrome secondary to systemic lupus erythematosus with Addison disease after the examination, such as blood cortisol, adrenocorticotropic hormone rhythm, and antiphospholipid antibody, who was improved clinically after hormone, anti-infective, and anticoagulant treatment. The patient's condition was stable in the follow-up. In clinic, we should pay attention to adrenal damage in patients with connective tissue diseases such as systemic lupus erythematosus and antiphospholipid antibody syndrome, and be alert to the occurrence of adrenal crisis.The clinical data for a patient with pulmonary hypertension complicating mediastinal fibrosis secondary to tuberculosis admitted to the Second Xiangya Hospital, Central South University has been retrospectively analyzed, and the relevant literature has been reviewed. SB505124 inhibitor A 55-year-old Han Chinese woman initially presented with increasing shortness of breath on exertion for 7 months was admitted to our hospital in August 2013. Admission examination revealed an increased erythrocyte sedimentation rate, positive in T-SPOT TB test, multiform lesions in both lungs, the enlarged lymph nodes with calcification in mediastinum and bilateral hilar, the narrowed bilateral main bronchial lumen, and the thickened bilateral pleural, as well as adhesion band in the left pleural cavity under the thoracoscope. These results indicated that mycobacterium tuberculosis infection may be present. After 4 months of anti-tuberculosis treatment, there is no improvement in symptom of the patient. In 2016, the patient was admitted to our hoxplained pulmonary hypertension. Contrast-enhanced CT should be performed as early as possible to avoid mis-diagnosis or missed diagnosis.IgG4-related disease (IgG4-RD) is a recently recognized disorder characterized by elevated serum IgG4 levels and infiltration of IgG4 positive blood cells in the affected organs. However, other conditions like malignancy as well as connective tissue diseases, may show similar findings. A 56-year-old male patient visited Second Xiangya Hospital, Central South University for recurrent fever and chest pain for more than 1 month. Preliminary tests diagnosed as IgG4-related lung disease (IgG4-RLD). However, the improvement of symptoms was absent after the treatment with methylprednisolone. The patient underwent the second biopsy and the result eventually demonstrated lung adenocarcinoma. The role of IgG4 in the pathogenesis or prognosis for lung adenocarcinoma remains unclear. Therefore, a thorough evaluation of symptoms, test of specific serum markers and eventually pathological confirmation are required to avoid misdiagnosis.

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