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Burrowing as an index of inflammatory pain in male vs. female rats.

The study objective was to determine whether burrowing behavior is useful as a functional index of pain in both male and female rats, and whether a 'no-training' protocol can be used to increase testing efficiency. Adult Sprague-Dawley rats were injected in one or both hindpaws with oil vehicle or complete Freund's adjuvant (CFA); starting the next day, the amount of gravel each rat burrowed out of a tube in 1 h was measured daily for ≤7 days. Without preliminary training on the burrowing procedure, CFA reliably suppressed burrowing for 2-3 days compared to controls, in both sexes. However, whereas unilateral CFA completely suppressed burrowing 1-day post-CFA in nearly all males, bilateral CFA was required to do so in females. When administered 30 min before testing, once daily for 5 days post-CFA, the nonsteroidal anti-inflammatory drug ketoprofen (0.01-3.2 mg/kg) and the opioid morphine (0.1-3.2 mg/kg) significantly increased CFA-suppressed burrowing, whereas the purported cannabinoid analgesic Δ9-tetrahydrocannabinol (0.01-2.0 mg/kg) did not. The benzodiazepine chlordiazepoxide (1.25-10 mg/kg), included as a 'true negative' control, also did not restore CFA-suppressed burrowing in either sex. However, in CFA-treated males only, chlordiazepoxide decreased burrowing, suggesting that anxiety may contribute to burrowing in males but not females that are in pain. Overall these results suggest that burrowing is a valid, functional index of inflammatory pain in both sexes, and training on the burrowing procedure is not necessary. However, females are more avid burrowers than males, which should be considered when both sexes are used in inflammatory pain testing.

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Efficacy of High-Voltage Pulsed Radiofrequency of the Dorsal Root Ganglion for Treatment of Chronic Lumbosacral Radicular Pain: A Randomized Clinical Trial.

Pulsed radiofrequency (PRF) is an efficacious treatment for patients with lumbosacral radicular pain, but the optimal radiofrequency parameters are inadequately described. We hypothesized that high-voltage radiofrequency therapy around the dorsal root ganglion can be more effective and enduring than the standard voltage PRF therapy.

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Baicalein exerts anxiolytic and antinociceptive effects in a mouse model of posttraumatic stress disorder: Involvement of the serotonergic system and spinal delta-opioid receptors.

Post-traumatic stress disorder (PTSD) is a serious mental disease featured by a stress disfunction that occurs after an individual has faced intense mental stress, often accompanied by anxiety and chronic pain. Currently, the mainstream drug for PTSD is serotonin reuptake inhibitors (SSRIs), however, their pain management for patients is limited. Baicalein, a Chinese traditional herbal medicine. Has shown promising results in treating anxiety, depression, and pain. In this study, we found that baicalein may alleviate single prolonged stress (SPS)-induced PTSD-like behaviors in mice without altering baseline nociceptive sensitivity or activity. Meanwhile, baicalein increased the noradrenaline (NE) and serotonin (5-HT) content and decreased the ratio of 5-hydroxyindoleacetic acid (5-HIAA)/5-HT by inhibiting the activity of monoamine oxidase A (MAO-A) in SPS-induce mice. The anxiolytic and antinociceptive effects induced by baicalein were totally abolished by 5-HT depleting agents. Moreover, the anxiolytic effects of baicalein could be abolished by the 5-HT1A receptor antagonist WAY-100635, and the analgesic effects could be abolished by delta-opioid receptor antagonists in the spinal. Taken together, our study provides compelling evidence that baicalein reversed anxiety-like behaviors and neuropathic pain in PTSD through serotonergic system and spinal delta-opioid receptors.

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Clinician-administered performance-based tests via telehealth in people with chronic lower limb musculoskeletal disorders: Test-retest reliability and agreement with in-person assessment.

Uptake of telehealth has surged, yet no previous studies have evaluated the clinimetric properties of clinician-administered performance-based tests of function, strength, and balance via telehealth in people with chronic lower limb musculoskeletal pain. This study investigated the: (i) test-retest reliability of performance-based tests via telehealth, and (ii) agreement between scores obtained via telehealth and in-person.

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Modulation of central pain mechanisms using high definition transcranial direct current stimulation: A double-blind, sham-controlled study.

The use of high definition transcranial direct current stimulation (HD-tDCS) has shown analgesic effects in some chronic pain patients, but limited anti-nociceptive effects in healthy asymptomatic subjects. This double-blinded sham-controlled study assessed the effects of HD-tDCS applied on three consecutive days on central pain mechanisms in healthy participants with (N=40) and without (N=40) prolonged experimental pain induced by intramuscular injection of nerve growth factor into the right hand on Day1. Participants were randomly assigned to Sham-tDCS (N=20 with pain, N=20 without) or Active-tDCS (N=20 with pain, N=20 without) targeting simultaneously the primary motor cortex and dorsolateral prefrontal cortex for 20 min with 2mA stimulation intensity. Central pain mechanisms were assessed by cuff-algometry on the legs measuring pressure pain sensitivity, temporal summation of pain (TSP) and conditioned pain modulation (CPM), at baseline and after HD-tDCS on Day2 and Day3. Based on subject's assessment of received HD-tDCS (sham or active) they were effectively blinded. Compared with Sham-tDCS, Active-tDCS did not significantly reduce the average NGF-induced pain intensity. Tonic pain-induced temporal summation at Day2 and Day3 was significantly lower in the NGF-pain group under Active-tDCS compared to the pain group with Sham-tDCS (P≤0.05). No significant differences were found in the cuff pressure pain detection/tolerance thresholds or CPM effect across the 3 days of HD-tDCS in any of the four groups. HD-tDCS reduced the facilitation of TSP caused by tonic pain suggesting that efficacy of HD-tDCS might depend on the presence of sensitized central pain mechanisms.

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Intraarticular Injections of Mesenchymal Stem Cells in Knee Osteoarthritis: A Review of Their Current Molecular Mechanisms of Action and Their Efficacy.

More than 10% of the world's population suffers from osteoarthritis (OA) of the knee, with a lifetime risk of 45%. Current treatments for knee OA pain are as follows: weight control; oral pharmacological treatment (non-steroidal anti-inflammatory drugs, paracetamol, opioids); mechanical aids (crutches, walkers, braces, orthotics); therapeutic physical exercise; and intraarticular injections of corticosteroids, hyaluronic acid, and platelet-rich plasma (PRP). The problem is that such treatments usually relieve joint pain for only a short period of time. With respect to intraarticular injections, corticosteroids relieve pain for several weeks, while hyaluronic acid and PRP relieve pain for several months. When the above treatments fail to control knee pain, total knee arthroplasty (TKA) is usually indicated; however, although a very effective surgical technique, it can be associated with medical and postoperative (surgery-related) complications. Therefore, it seems essential to look for safe and effective alternative treatments to TKA. Recently, there has been much research on intraarticular injections of mesenchymal stem cells (MSCs) for the management of OA of the knee joint. This article reviews the latest information on the molecular mechanisms of action of MSCs and their potential therapeutic benefit in clinical practice in patients with painful knee OA. Although most recent publications claim that intraarticular injections of MSCs relieve joint pain in the short term, their efficacy remains controversial given that the existing scientific information on MSCs is indecisive. Before recommending intraarticular MSCs injections routinely in patients with painful knee OA, more studies comparing MSCs with placebo are needed. Furthermore, a standard protocol for intraarticular injections of MSCs in knee OA is needed.

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Expanding the clinical spectrum of idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a disorder of raised intracranial pressure (ICP). Although the majority of patients with IIH present classically with headache and papilledema, some patients may have unusual presentations or manifestations. Recent advancements in neuroimaging have facilitated the identification of other presentations associated with IIH. This review provides an overview of the expanding clinical spectrum of IIH.

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Pharmacological Interventions for Opioid-Induced Hyperalgesia: A Scoping Review of Preclinical Trials.

Opioid analgesics are the most effective pharmacological agents for moderate and severe pain. However, opioid use has several limitations such as opioid-induced hyperalgesia (OIH), which refers to the increased pain sensitivity that occurs once analgesia wears off after opioid administration. Several pharmacological interventions have been suggested for OIH, but the current literature does not provide guidelines on which interventions are the most effective and whether they differ depending on the opioid that induces hyperalgesia. This scoping review aimed to identify and describe all the preclinical trials investigating pharmacological interventions for OIH caused by remifentanil, fentanyl, or morphine as the first step towards evaluating whether the most effective OIH interventions are different for different opioids.

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Phloroglucinol-Derived Medications are Effective in Reducing Pain and Spasms of Urinary and Biliary Tracts: Results of Phase 3 Multicentre, Open-Label, Randomized, Comparative Studies of Clinical Effectiveness and Safety.

Pain and spasms of urinary and biliary tracts are conditions causing poor quality of life. Treatment with analgesic drugs such as non-steroidal anti-inflammatory drugs and modulators of the parasympathetic system are not always tolerated, and often additional therapeutic options are necessary. The present analysis aimed to evaluate the pharmacokinetics and effectiveness of oral and parenteral preparations based on phloroglucinol in reducing pain and spasms associated with renal or biliary colic in phase 3, multicentre, open-label, randomized, comparative studies on clinical effectiveness and safety.

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Antiracism CoaliTION in Pain Research (ACTION-PR): Guiding Principles for Equity in Reporting.

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