Pain
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Randomized Controlled Trial Multicenter Study
Safety and efficacy of an equimolar mixture of oxygen and nitrous oxide (EMONO): a randomized controlled trial in patients with peripheral neuropathic pain.
Nitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia and for short-duration analgesia in various clinical settings mostly in the form of an N2O/O2 50%-50% equimolar mixture (EMONO). Experimental studies have suggested that EMONO could also induce long-lasting analgesic effects related to the blockade of N-methyl-D-aspartate receptors. We designed the first international multicenter proof of concept randomized, placebo-controlled study to assess the efficacy and safety of a 1-hour administration of EMONO or placebo (medical air) on 3 consecutive days up to 1 month after the last administration in patients with chronic peripheral neuropathic pain. ⋯ However, evoked pain intensity (predefined secondary endpoint) and Patient Global Impression of Change (exploratory endpoint) were significantly improved in the EMONO group, and these effects were maintained up to 4 weeks after the last treatment administration. Mostly transient side effects were reported during the treatment administration. These encouraging results provide a basis for further investigation of the long-term analgesic effects of EMONO in patients with neuropathic pain.
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Randomized Controlled Trial Multicenter Study
Trauma-focused cognitive behavioural therapy and exercise for chronic whiplash with comorbid posttraumatic stress disorder: a randomised controlled trial.
Many people with chronic whiplash-associated disorders (WAD) have also symptoms of posttraumatic stress disorder (PTSD), but this is rarely considered in usual predominantly exercise-based interventions. We aimed to investigate the effectiveness of combined trauma-focused cognitive behavioural therapy (TF-CBT) and exercise compared with supportive therapy (ST) and exercise for people with chronic WAD and PTSD. A randomised controlled multicentre trial with concealed allocation, assessor blinding, and blinded analysis was conducted. ⋯ Exceptions were in favour of TF-CBT and exercise, where improvements in PTSD symptoms were found at 16 weeks. From 16 weeks onwards, both groups achieved a clinically important improvement in neck pain-related disability. However, both groups remained moderately disabled.
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Sex differences for chronic back pain (cBP) have been reported, with females usually exhibiting greater morbidity, severity, and poorer response to treatment. Genetic factors acting in an age-specific manner have been implicated but never comprehensively explored. We performed sex- and age-stratified genome-wide association study and single nucleotide polymorphism-by-sex interaction analysis for cBP defined as "Back pain for 3+ months" in 202,077 males and 237,754 females of European ancestry from UK Biobank. ⋯ There was a stronger genetic correlation of cBP with self-reported diagnosis of intervertebral disk degeneration in males than in females (0.889 vs 0.638; P = 3.7E-06). Thus, the genetic component of cBP in the UK Biobank exhibits a mild sex- and age-dependency. This provides an insight into the possible causes of sex- and age-specificity in epidemiology and pathophysiology of cBP and chronic pain at other anatomical sites.
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Mechanisms of visceral pain sensitization and referred somatic hypersensitivity remain unclear. We conducted calcium imaging in Pirt-GCaMP6s mice to gauge responses of dorsal root ganglion (DRG) neurons to visceral and somatic stimulation in vivo. Intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colonic inflammation and increased the percentage of L6 DRG neurons that responded to colorectal distension above that of controls at day 7. ⋯ Visceral irritation from intracolonic capsaicin instillation also increased Evans blue extravasation in hind paws and low-back skin and acutely increased the percentage of L4 DRG neurons responding to hind paw pinch and the response of L6 DRG neurons to low-back brush stimulation. These findings suggest that TNBS-induced colitis and capsaicin-induced visceral irritation may sensitize L6 DRG neurons to colorectal and somatic inputs and also increase the excitability of L4 DRG neurons that do not receive colorectal inputs. These changes may represent a potential peripheral neuronal mechanism for visceral pain sensitization and referred somatic hypersensitivity.
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The voltage-gated sodium channel Nav1.7 is highly expressed in nociceptive afferents and is critically involved in pain signal transmission. Nav1.7 is a genetically validated pain target in humans because loss-of-function mutations cause congenital insensitivity to pain and gain-of-function mutations cause severe pain syndromes. Consequently, pharmacological inhibition has been investigated as an analgesic therapeutic strategy. ⋯ In the spared nerve injury model of neuropathic pain, ST-2530 transiently reversed mechanical allodynia. These analgesic effects were demonstrated at doses that did not affect locomotion, motor coordination, or olfaction. Collectively, results from this study indicate that pharmacological inhibition of Nav1.7 by a small molecule agent with affinity for the resting state of the channel is sufficient to produce analgesia in a range of preclinical pain models.