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Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, systemic, inflammatory diseases, primarily in the musculoskeletal system. Pain and fatigue are key symptoms of RA and AS. Treatment presents a clinical challenge for several reasons, including the progressive nature of the diseases and the involvement of multiple pain mechanisms. Moreover, side effects of pain treatment pose an implicit risk. Currently, no well-controlled studies have investigated how medical cannabis affects pain and cognitive functions in RA and AS. The present study aims to evaluate the efficacy and safety of medical cannabis in the treatment of persistent pain in patients with RA and AS with low disease activity.
Learn More >Monoclonal antibodies (mAbs) targeting the CGRP pathway are safe and efficacious therapies for the prevention of migraine. In this study we assessed the effects of discontinuation of preventive erenumab and galcanezumab treatment in patients with chronic migraine.
Learn More >Cluster headache stands among the worst debilitating pain conditions. Available treatments for cluster headache have often disabling side effects, are not tolerated, or are ineffective. The management of drug-refractory chronic forms is challenging. New treatments are warranted and reported here.
Learn More >Phantom limb pain (PLP) is a disabling and intractable sensation arising in about 80% of patients after amputation. The aim of this study was to evaluate the possibility to modulate nociceptive processing and pain perception with cerebellar transcranial direct current stimulation (ctDCS) in patients suffering from painful and non-painful phantom limb sensations. Fourteen upper limb amputees underwent ctDCS (anodal or sham, 2.0 mA, 20 min per day, 5 days a week). Clinical scores and electrophysiological parameters were assessed before tDCS, at the end of the 5-day treatment, 2 and 4 weeks later. Laser-evoked potentials (LEPs) were obtained from the stump using a Nd:YAP laser by pulses with short duration (5 ms) and small diameter spots (5 mm). Changes in visual analogue scores (VAS) were evaluated (chronic pain, paroxysmal pain, stump pain, phantom movements, phantom sensations). Anodal polarization significantly dampened LEP amplitudes (N1, p = 0.021 and N2/P2, p = 0.0034), whereas sham intervention left them unchanged. Anodal ctDCS significantly reduced paroxysmal pain (p < 0.0001), non-painful phantom limb sensations (p < 0.0001) and phantom limb movements (p = 0.0003), whereas phantom limb and stump pain did not change compared to the sham condition. Anodal ctDCS significantly improves both paroxysmal pain and non-painful phantom limb sensations, which are likely induced by maladaptive changes in the sensorimotor network and posterior parietal cortex respectively.
Learn More >Recent neuroimaging studies implicate the medial temporal lobe (MTL) in nociception and pain modulation. Here, we aim to identify which subregions of the MTL are involved in human pain and to test its connectivity in a cohort of chronic low back pain patients (CBP). We conducted two coordinate-based meta-analyses to determine which regions within the MTL showed consistent spatial patterns of functional activation (1) in response to experimental pain in healthy participants, and (2) in chronic pain compared to healthy participants. We followed PRISMA guidelines and performed activation likelihood estimate (ALE) meta-analyses. The first meta-analysis revealed consistent activation in the right anterior hippocampus (right antHC), parahippocampal gyrus and amygdala. The second meta-analysis revealed consistently less activation in patients' right antHC, compared to healthy participants. We then conducted a seed-to-voxel resting state functional connectivity of the right antHC seed with the rest of the brain in 77 CBP and 79 age-matched healthy participants. We found that CBP had significantly weaker antHC functional connectivity to the medial prefrontal cortex (mPFC) compared to healthy participants. Taken together, these data indicate that the antHC has abnormally lower activity in chronic pain, and reduced connectivity to the mPFC in CBP. Future studies should investigate the specific role of the antHC in the development and management of chronic pain.
Learn More >The aim of this study was to evaluate skeletal pain associated with osteoporosis and examine the inhibitory effect of interleukin-6 (IL-6) on pain in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated by examining pain-related behavior and immunohistochemistry. The effects of IL-6 receptor inhibitor (IL-6i) on these parameters were also assessed. Eight-week-old female ddY mice were ovariectomized and assigned to three groups: OVX mice treated with vehicle (OVX); OVX mice treated with alendronate (OVX-ALN); and OVX mice treated with anti-IL-6 receptor (anti-IL-6R) antibody (OVX-IL6i). Sham-operated mice were treated with vehicle. Immediately after surgery, vehicle, ALN, or anti-IL-6R antibody was injected subcutaneously. After a 4-week treatment, mechanical sensitivity was examined using von Frey filaments. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally with micro-computed tomography. Calcitonin gene-related peptide (CGRP) expression in L3-L5 dorsal root ganglion (DRG) neurons was examined using immunohistochemistry. Ovariectomy induced bone loss and mechanical hyperalgesia in the hindlimbs with upregulation of CGRP expression in the DRG neurons innervating the hindlimbs. ALN treatment prevented bone loss, but anti-IL-6R antibody treatment had no effect on bone morphometry compared with that of the OVX group. However, mechanical hyperalgesia and CGRP expression were significantly decreased in the OVX-IL6i and OVX-ALN groups compared with those in the OVX group. Although anti-IL-6R antibody treatment had no effect on ovariectomy-induced bone loss, the treatment prevented ovariectomy-induced mechanical hyperalgesia in the hindlimbs and suppressed CGRP expression in DRG neurons. The results suggest that IL-6 is one of the causes of postmenopausal osteoporotic pain, and anti-IL-6R antibody might preserve bone health and decrease osteoporotic pain.
Learn More >Few investigators have developed and tested nonpharmacological interventions for helping persons with sickle cell disease (SCD) manage persistent pain.
Learn More >Opioid-induced respiratory depression results in part from direct activation of μ-opioid receptors expressed in the inspiratory rhythm generator located in the ventrolateral medulla, the preBötzinger ComplexRespiratory neurons within the medulla also express nicotinic acetylcholine receptors, which are made up of five subunits, arranged symmetrically around a central poreActivation of the nicotinic acetylcholine receptor α4, α7, and β2 subunits increases respiratory rhythm, whereas activation of the nicotinic acetylcholine receptor α4β2 or α7 subunits induces analgesia in multiple forms of pain WHAT THIS ARTICLE TELLS US THAT IS NEW: The nonselective nicotinic acetylcholine receptor agonist nicotine and the α4β2 nicotinic acetylcholine receptor agonist A85380, but not the α7 nicotinic acetylcholine receptor agonist PNU282987, reversed respiratory depression induced by activation of μ-opioid receptors in rats both in vitro and in vivoCoadministration of A85380 with fentanyl not only markedly reduced respiratory depression and apneas but also enhanced the fentanyl-induced analgesia BACKGROUND:: Opioid analgesics are widely used for treatment of acute, postoperative, and chronic pain. However, activation of opioid receptors can result in severe respiratory depression. There is an unmet clinical need to develop a pharmacologic therapy to counter opioid-induced respiratory depression without interfering with analgesia. Further, additional advances to confront accidental lethal overdose with the use of fentanyl and other opioids are needed. Here, the authors test the hypothesis that activation of nicotinic receptors expressed within respiratory rhythm-generating networks would counter opioid-induced respiratory depression without compromising analgesia.
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