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Cohort/psychometric study OBJECTIVES: The primary objective was to determine the psychometric properties and the utility of the Neuropathic Pain Symptom Inventory (NPSI) in subgrouping people with moderate to severe neuropathic pain after spinal cord injury (SCI).
Learn More >Migraine is one of the most disabling neurological diseases worldwide; however, the mechanisms underlying migraine headache are still not fully understood and current therapies for such pain are inadequate. It has been suggested that inflammation and neuroimmune modulation in the gastrointestinal tract could play an important role in the pathogenesis of migraine headache, but how gut microbiomes contribute to migraine headache is unclear. In the present study, we investigated the effect of gut microbiota dysbiosis on migraine-like pain using broad-spectrum antibiotics and germ-free (GF) mice. We observed that antibiotics treatment-prolonged nitroglycerin (NTG)-induced acute migraine-like pain in wild-type (WT) mice and the pain prolongation was completely blocked by genetic deletion of tumor necrosis factor-alpha (TNFα) or intra-spinal trigeminal nucleus caudalis (Sp5C) injection of TNFα receptor antagonist. The antibiotics treatment extended NTG-induced TNFα upregulation in the Sp5C. Probiotics administration significantly inhibited the antibiotics-produced migraine-like pain prolongation. Furthermore, NTG-induced migraine-like pain in GF mice was markedly enhanced compared to that in WT mice and gut colonization with fecal microbiota from WT mice robustly reversed microbiota deprivation-caused pain enhancement. Together, our results suggest that gut microbiota dysbiosis contributes to chronicity of migraine-like pain by upregulating TNFα level in the trigeminal nociceptive system.
Learn More >While the prevalence of pain increases with age, too much medication can lead to negative side effects. Complementary approaches, such as clinical hypnosis, could be relevant in pain management. While evidence in the literature has shown that clinical hypnosis is effective in child and adult populations, there have been few studies in aging populations. Furthermore, the feasibility and effectiveness of clinical hypnosis in preventive home care in elderly populations with pain have never been established. The goal of this within-subject study was to determine the feasibility and the effects of three 15-min hypnosis sessions delivered during home care interventions over a 12-week period in 15 elderly women with chronic pain (mean age, 81 years; range, 65-87 years).
Learn More >Lasmiditan demonstrated superiority to placebo in the acute treatment of migraine in adults with moderate/severe migraine disability in two similarly designed Phase 3 trials, SAMURAI and SPARTAN. Post-hoc integrated analyses evaluated the efficacy of lasmiditan in patients who reported a good or insufficient response to triptans and in those who were triptan naïve.
Learn More >Ceruletide (CRL) is a decapeptide, originating from the skin of a tropical frog, and is many times more potent that cholecystokinin (CCK) in a number of assays. The compound was first isolated and characterized around 50 years ago, and its analgesic properties were subsequently identified. Since the 1980s it has been available in the clinic as a parenteral solution and is used as a diagnostic tool to characterize pancreas and gall bladder malfunctions. Its analgesic properties were evaluated in a number of indications: cancer pain, burns, colic pains and migraine. Preclinically, CRL reduces pain in low microgram dose range and promotes clear and long-lasting analgesic activity in nanograms when applied centrally. CCK is amongst the most widely expressed neuropeptides in the brain. CCK-induced analgesic effects in response to persistent and inflammatory pain have recently been associated with CCK2 receptor signaling. CRL, a potent CCK agonist, might be worthwhile to rediscover as a putative analgesic drug and could represent a potential analgesic intrathecal strategy to patients with cancer-related pain.
Learn More >Since the first discovery that the bioactive lipid, lysophosphatidic acid (LPA) and LPA receptor signaling play a role in the initiation of neuropathic pain (NeuP), accumulated reports have supported the original findings and extended the study toward possible therapeutic applications. The present review describes beneficial roles of LPA receptor signaling in a variety of chronic pain, such as peripheral NeuP induced by nerve injury, chemotherapy and diabetes, central NeuP induced by cerebral ischemia with hemorrhage and spinal cord injury, and fibromyalgia-like wide spread pain induced by repeated cold, psychological and muscular acidic stress. Emerging mechanistic findings are the feed-forward amplification of LPA production through LPA, LPA and microglia and the evidence for maintenance of chronic pain by LPA receptor signaling.
Learn More >Orthopedic injury can occur from a variety of causes including motor vehicle collision, battlefield injuries or even falls from standing. Persistent limb pain is common after orthopedic injury or surgery and presents a unique challenge, as the initiating event may result in polytrauma to bone, muscle, and peripheral nerves. It is imperative that we understand the tissue-specific and multicellular response to this unique type of injury in order to best develop targeted treatments that improve healing and regeneration. In this Mini Review we will first discuss current rodent models of orthopedic trauma/complex orthotrauma. In the second section, we will focus on bone-specific outcomes including imaging modalities, biomechanical testing and immunostaining for markers of bone healing/turnover. In the third section, we will discuss muscle-related pathology including outcome measures of fibrosis, muscle regeneration and tensile strength measurements. In the fourth section, we will discuss nervous system-related pathology including outcome measures of pain-like responses, both reflexive and non-reflexive. In all sections we will consider parallels between preclinical outcome measures and the functional and mechanistic findings of the human condition.
Learn More >The role of gonadal hormones in neural plasticity remains unclear. This study aimed to examine the effects of naturally fluctuating hormone levels over the menstrual cycle in healthy females. Gray matter, functional connectivity (FC) and white matter changes over the cycle were assessed by using functional magnetic resonance imaging (fMRI), resting state fMRI, and structural MRIs, respectively, and associated with serum gonadal hormone levels. Moreover, electrocutaneous sensitivity was evaluated in 14 women in four phases of their menstrual cycle (menstrual, follicular, ovulatory, and luteal). Electrocutaneous sensitivity was greater during follicular compared to menstrual phase. Additionally, pain unpleasantness was lower in follicular phase than other phases while pain intensity ratings did not change over the cycle. Significant variations in cycle phase effects on gray matter volume were found in the left inferior parietal lobule (IPL) using voxel-based morphometry. Subsequent Freesurfer analysis revealed greater thickness of left IPL during the menstrual phase when compared to other phases. Also, white matter volume fluctuated across phases in left IPL. Blood estradiol was positively correlated with white matter volume both in left parietal cortex and whole cortex. Seed-driven FC between left IPL and right secondary visual cortex was enhanced during ovulatory phase. A seed placed in right IPL revealed enhanced FC between left and right IPL during the ovulatory phase. Additionally, we found that somatosensory cortical gray matter was thinner during follicular compared to menstrual phase. We discuss these results in the context of likely evolutionary pressures selecting for enhanced perceptual sensitivity across modalities specifically during ovulation.
Learn More >The clinical presentation of neck-arm pain is heterogeneous with varying underlying pain types (nociceptive/neuropathic/mixed) and pain mechanisms (peripheral/central sensitization). A mechanism-based clinical framework for spinally referred pain has been proposed, which classifies into (1) somatic pain, (2) neural mechanosensitivity, (3) radicular pain, (4) radiculopathy and mixed pain presentations. This study aims to (i) investigate the application of the clinical framework in patients with neck-arm pain, (ii) determine their somatosensory, clinical and psychosocial profile and (iii) observe their clinical course over time.
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