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Sensory neurons exhibit sex-dependent responsiveness to prolactin (PRL). This could contribute to sexual dimorphism in pathological pain conditions. The aim of this study is to elucidate mechanisms underlying sex-dependent PRL sensitivity in sensory neurons. Quantitative RT-PCR show that prolactin receptor (Prlr) long and short isoform mRNAs are expressed at comparable levels in female and male mouse dorsal root ganglia (DRG). In Prlr ;Rosa26 reporter mice, percentages of Prlr sensory neurons in female and male DRG are also similar. Characterization of Prlr DRG neurons using immunohistochemistry and electrophysiology revealed that Prlr DRG neurons are mainly peptidergic nociceptors in females and males. However, sensory neuron type-dependent expression of Prlr is sex dimorphic. Thus, Prlr populations fell into three small- and two medium-large-sized sensory neuronal groups. Prlr DRG neurons are predominantly medium-large sized in males and are proportionally more comprised of small-sized sensory neurons in females. Specifically, Prlr /IB4 /CGRP neurons are 4-5-fold higher in numbers in female DRG. In contrast, Prlr /IB4 /CGRP /5HT3a /NPYR2 are predominant in male DRG. Prlr /IB4 /CGRP , Prlr /IB4 /CGRP and Prlr /IB4 /CGRP /NPYR2 neurons are evenly encountered in female and male DRG. These differences were confirmed using an independently generated single-cell sequencing dataset. Overall, we propose a novel mechanism whereby sensory neuron type-dependent expression of Prlr could explain the unique sex dimorphism in responsiveness of nociceptors to PRL. This article is protected by copyright. All rights reserved.
Learn More >Chronic pain is an important problem after critical care admission. Estimates of the prevalence of chronic pain in the year after discharge range from 14% to 77% depending on the type of cohort, the tool used to measure pain, and the time point when pain was assessed. The majority of data available come from studies using health-related quality of life tools, although some have included pain-specific tools. Nociceptive, neuropathic, and nociplastic pain can occur in critical care survivors, but limited information about the aetiology, body site, and temporal trajectory of pain is currently available. Older age, pre-existing pain, and medical co-morbidity have been associated with pain after critical care admission. No trials were identified of interventions to target chronic pain in survivors specifically. Larger studies, using pain-specific tools, over an extended follow-up period are required to confirm the prevalence, identify risk factors, explore any association between acute and chronic pain in this setting, determine the underlying pathological mechanisms, and inform the development of future analgesic interventions.
Learn More >Treatment with cannabidiol (CBD) or KLS-13019 (novel CBD analog), has previously been shown to prevent paclitaxel-induced mechanical allodynia in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). The mechanism of action for CBD- and KLS-13019-mediated protection now has been explored with dissociated dorsal root ganglion (DRG) cultures using small interfering RNA (siRNA) to the mitochondrial Na Ca exchanger-1 (mNCX-1). Treatment with this siRNA produced a 50-55% decrease in the immunoreactive (IR) area for mNCX-1 in neuronal cell bodies and a 72-80% decrease in neuritic IR area as determined with high-content image analysis. After treatment with 100 nM KLS-13019 and siRNA, DRG cultures exhibited a 75 ± 5% decrease in protection from paclitaxel-induced toxicity; whereas siRNA studies with 10 μM CBD produced a 74 ± 3% decrease in protection. Treatment with mNCX-1 siRNA alone did not produce toxicity. The protective action of cannabidiol and KLS-13019 against paclitaxel-induced toxicity during a 5-h test period was significantly attenuated after a 4-day knockdown of mNCX-1 that was not attributable to toxicity. These data indicate that decreases in neuritic mNCX-1 corresponded closely with decreased protection after siRNA treatment. Pharmacological blockade of mNCX-1 with CGP-37157 produced complete inhibition of cannabinoid-mediated protection from paclitaxel in DRG cultures, supporting the observed siRNA effects on mechanism.
Learn More >As new migraine prevention treatments are developed, the onset of a preventive effect, how long it is maintained and whether patients initially non-responsive develop clinically meaningful responses with continued treatment can be assessed.
Learn More >We aimed to evaluate the role of caffeinated beverage intake as a potential trigger of migraine headaches on that day or on the following day.
Learn More >Although chronic postsurgical pain (CPSP) is a major health care problem, pain-related functional interference has rarely been investigated. Using the PAIN OUT registry, we evaluated patients' pain-related outcomes on the first postoperative day, and their pain-related interference with daily living (Brief Pain Inventory) and neuropathic symptoms (DN4: douleur neuropathique en 4 questions) at 6 months after surgery. Endpoints were pain interference total scores (PITS) and their association with pain and DN4 scores. Furthermore, possible risk factors associated with impaired function at M6 were analyzed by ordinal regression analysis with PITS groups (no to mild, moderate, and severe interference) as a dependent three-stage factor. Odds ratios with 95% confidence intervals were calculated. Of 2322 patients, 15.3% reported CPSP with an average pain score ≥3 (numeric rating scale 0-10). Risk for a higher PITS group increased by 190% (odds ratio [95% confidence interval]: 2.9 [2.7-3.2]; P < 0.001) in patients with CPSP, compared to without CPSP. A positive DN4 independently increased risk by 29% (1.3 [1.12-1.45]; P < 0.001). Preexisting chronic pain (3.6 [2.6-5.1]; P < 0.001), time spent in severe acute pain (2.9 [1.3-6.4]; P = 0.008), neurosurgical back surgery in males (3.6 [1.7-7.6]; P < 0.001), and orthopedic surgery in females (1.7 [1.0-3.0]; P = 0.036) were the variables with strongest association with PITS. Pain interference total scores might provide more precise information about patients' outcomes than pain scores only. Because neuropathic symptoms increase PITS, a suitable instrument for their routine assessment should be defined.
Learn More >Numerous reports highlight variations in pain clinic provision between services, particularly in the provision of multidisciplinary services and length of waiting times. A National Audit aims to identify and quantify these variations, to facilitate raising standards of care in identified areas of need. This article describes a Quality Improvement Programme cycle covering England and Wales that used such an approach to remedy the paucity of data on the current state of UK pain clinics.
Learn More >An evaluation of the behavioral inhibition and behavioral activation system (BIS-BAS) model of pain.
This study evaluated the behavioral inhibition and activation system (BIS-BAS) model of pain. Frontal alpha asymmetry (FAA) as a possible neurophysiological correlate of the BIS-BAS was also explored, as was the role of personality factors.
Learn More >N-methyl-D-aspartate (NMDA) receptors are involved in pain signalling and neuroplasticity. Memantine has been shown to have analgesic properties in pre-clinical and small clinical studies. We conducted a systematic review and meta-analysis to assess the efficacy of memantine to prevent or reduce chronic pain.
Learn More >Consciousness, defined here as the quality of awareness of self and the corresponding sensory environment, is considered to be one of most enigmatic and contentious areas of scholarly dissection and investigation. The subjective experience of pain is constructed and modulated by a myriad of sensory, cognitive and affective dimensions. Thus, the study of pain can provide many inroads to a concept like consciousness that the traditional sense modalities do not. Mindfulness defined here as non-reactive awareness of the present moment, can uniquely control and/or modulate particular substrates of conscious experience. Thus, in combination with brain imaging methodologies, we propose that the interactions between pain and mindfulness could serve as a more comprehensive platform to disentangle the biological and psychological substrates of conscious experience. The present review provides a brief synopsis on how combining the study of pain and mindfulness can inform the study of consciousness, delineates the multiple, unique brain mechanisms supporting mindfulness-based pain relief, and describes how mindfulness uniquely improves the affective dimension of pain, an important consideration for the treatment of chronic pain.
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