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In this randomized clinical trial, we examined whether the effect of true acupuncture can be differentiated from sham acupuncture (pain and functionality) by analyzing quantitative sensory testing (QST) profiles in chronic pain participants. We recruited 254 healthy or chronic back and neck pain participants. Healthy subjects were included to control for a possible effect of acupuncture on baseline QST changes. Study participants received six sessions (twice weekly) of true acupuncture, sham acupuncture, or no acupuncture treatment (routine care). QST profiles, pain scores and functionality profile were obtained at baseline (visit 1) and after 3 (visit 4) or 6 sessions (visit 7). A total of 204 participants were analyzed. We found no QST profile changes among three groups (P = 0.533 and P = 0.549, Likelihood-ratio tests) in either healthy or chronic pain participants. In chronic back and neck pain participants, true acupuncture reduced pain [visit 4: DIM (difference in mean) = -0.8, 95% CI: -1.4 to -0.1, adjusted P = 0.168; visit 7: DIM = -1.0, 95% CI: -1.7 to -0.3, adjusted P = 0.021) and improved functional status including physical functioning (DIM = 14.21, 95% CI: 5.84 to 22.58, adjusted P = 0.003) and energy/fatigue (DIM = 12.28, 95% CI: 3.46 to 21.11, adjusted P = 0.021) as compared to routine care. Our results indicate that QST was not helpful to differentiate between true acupuncture and sham acupuncture (primary outcome) in this study, although true acupuncture reduced pain and improved functionality (secondary outcomes) when compared with routine care.
Learn More >The field of biased agonism has grown substantially in recent years and the μ opioid receptor has been one of the most intensively studied receptor targets for developing biased agonists. Yet, despite extensive research efforts the development of analgesics with reduced adverse effects remains a significant challenge. In this review we discuss the evidence to support the prevailing hypothesis that a G protein biased agonist at the μ opioid receptor would be an effective analgesic without the accompanying adverse effects associated with conventional μ opioid agonists. We also assess the current status of established and novel μ opioid receptor ligands that are proposed to be biased ligands. SIGNIFICANCE STATEMENT: The idea that biased agonists at the &[mu] opioid receptor might provide a therapeutic advantage in terms of producing effective analgesia but with fewer adverse effects has driven the design of novel G protein-biased agonists. However is the desirability of G protein-biased agonists at &[mu] opioid receptor substantiated by what we know of the physiology and pharmacology of the receptor? Also do any of the novel biased agonists live up to their initial promise? Here we address these issues by critically examining the evidence that G protein bias really is desirable and also by discussing whether the ligands so far developed are clearly biased in vitro and whether this produces responses in vivo that might be commensurate with such bias.
Learn More >Satellite glial cells (SGCs) activation in the trigeminal ganglia (TG) is critical in various abnormal orofacial sensation in nerve injury and inflammatory conditions. SGCs express several subtypes of P2 purinergic receptors contributing to the initiation and maintenance of neuropathic pain. The P2Y receptor, a G-protein-coupled receptor activated by uridine diphosphate (UDP)-glucose and other UDP sugars, mediates various physiologic events such as immune, inflammation, and pain. However, the expression, distribution, and function of P2Y receptor in SGCs remains largely unexplored. Our study reported the expression and functional identification of P2Y receptor in SGCs. SGCs were isolated from TG of rat, and the P2Y receptor expression was examined using immunofluorescence technique. Cell proliferation and viability were examined via cell counting kit-8 experiment. Immunofluorescence demonstrated the presence of P2Y receptor in SGCs. Immunofluorescence and western blot showed that UDP-glucose treatment upregulated glial fibrillary acid protein, a common marker for glial activation. Extracellular UDP-glucose enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, which were both abolished by the P2Y receptor inhibitor (PPTN). Furthermore, quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay demonstrated that extracellular UDP-glucose significantly enhanced interleukin-1β (IL-1β) and chemokine CCL2 (CCL2) release, which was abolished by PPTN and significantly decreased by inhibitors of MEK/ERK (U0126) and p38 (SB202190). Our findings directly proved the functional presence of P2Y receptor in SGCs. It was also verified that P2Y receptor activation was involved in activating SGCs, phosphorylating MAPKs, and promoting the secretion of IL-1β and CCL2 via ERK and p38 pathway.
Learn More >Red cell transfusions are one of the most common and important therapies used for patients with sickle cell disease (SCD). For prevention of strokes, there is abundant evidence that transfusions are efficacious, whereas for other indications, such as prevention of pain, there are less data. Nonetheless, with few therapeutic options, the use of transfusion for prevention of acute pain has increased in children and adults with SCD without a clear understanding of its benefits.
Learn More >Migraine affects an estimated 12% of the population. Global estimates are higher. Chronic migraine (CM) affects 1% to 2% of the global population. Approximately 2.5% of persons with episodic migraine progress to CM. Several risk factors are associated with the progression to CM. There is significant short-term variability in migraine frequency independent of treatment. Migraine is associated with cardiovascular disease, psychiatric disease, and sleep disorders. It is the second most disabling condition worldwide. CM is associated with higher headache-related disability/impact, medical and psychiatric comorbidities, health care resource use, direct and indirect costs, lower socioeconomic status, and health-related quality of life.
Learn More >Functional disorders (i.e., interstitial cystitis/painful bladder syndrome and irritable bowel syndrome) are associated with hyperexcitability of afferent nerves innervating the urinary tract and the bowel respectively. Various non-5-HT receptor mRNA transcripts are expressed in mouse urothelium and exert functional responses to 5-HT. Whilst 5-HT receptors were not detected in mouse urothelium, 5-HT receptors expressed on bladder sensory neurons plays a role in bladder afferent excitability under both normal conditions and in a mouse model of chronic visceral hypersensitivity (CVH). These data suggest that the role 5-HT receptors play in bladder afferent signaling warrants further study as a potential therapeutic target for functional bladder disorders.
Learn More >Chronic pain is a public health problem associated with opioid misuse. Yet, it is important to understand factors underlying opioid misuse in the context of pain. Alcohol use is one factor to consider given past work documenting use of alcohol to manage pain. However, it is unknown whether alcohol use severity exacerbates the relation between pain and opioid misuse. This study sought to examine relations between pain and prescription opioid misuse and the moderating role of alcohol use severity in two online survey studies of individuals with chronic pain.
Learn More >: Information on prescriptions of oral analgesics for the treatment of pain is beneficial. However, there have been few reports on the prescription status of oral analgesics from a nation-wide, large-scale prescription database in Japan. : The authors analyzed the prescription data of 2,042,302 patients prescribed oral analgesics in 2017. The numbers/proportions of patients prescribed oral analgesics, adherence with approved doses, co-prescription patterns, dose changes, drug adherence, and treatment-discontinuation rates were evaluated. : Loxoprofen was prescribed to 32.5% of the patients, followed by celecoxib, prescribed to 16.0% of patients. Acetaminophen and pregabalin were prescribed to 10.5% and 9.4% of patients, respectively. Many analgesics were prescribed at lower doses than the approved doses. The most frequently used concomitant medication was pregabalin. For duloxetine and pregabalin, high proportions of patients were prescribed these drugs for > 90 days. : Loxoprofen was the most prescribed of the non-steroidal anti-inflammatory drugs in Japan. The information obtained provides an overview of prescribed oral analgesics in Japan and could be useful for potential research into prescribed oral analgesics in the future.
Learn More >In the United States, chronic low-back pain affects up to 37% of adults and is a multi-billion dollar healthcare market. Spinal Cord Simulation (SCS) has been established as an effective treatment alternative for chronic neuropathic low-back and leg pain especially for patients suffering from Failed Back Surgery Syndrome (FBSS) or Chronic Regional Pain Syndrome (CRPS). The field of SCS has rapidly advanced such that analgesia can now be achieved through numerous different waveforms, each claiming to offer improved outcomes. These waveforms include traditional paresthesia-based stimulation (PB-SCS; <100 Hz), paresthesia-free high-frequency stimulation (HF-SCS; 5-10 kHz), burst stimulation, and sub-perception stimulation (SP-SCS; 1-5 kHz). Level 1 evidence critically evaluating the efficacy of these different waveforms is lacking. We conducted a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines to identify all randomized controlled trials (RCTs) of SCS in the treatment of chronic neuropathic low-back and leg pain, FBSS, or CRPS. A total of 38 eligible studies were reviewed to yield a final 13 RCTs that were included in our systematic review. We review the evidence from RCTs in the field of SCS that have established PB-SCS, HF-SCS, Burst, and SP-SCS as viable treatment options for chronic neuropathic low-back and leg pain. We critically evaluate the evidence that claims to support the use of one waveform over the other and review the literature on patient preference for different waveforms.
Learn More >The primary objective was to investigate the prevalence of neuropathic-like pain in patients with psoriatic arthritis (PsA). Secondary outcomes were to investigate whether mood, fatigue, pain, disease severity and fibromyalgia are associated with neuropathic-like pain in PsA patients.
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