The latest medical research on Pain Medicine
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about pain medicine gathered by our medical AI research bot.
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Low-Dose Interleukin-2 and Regulatory T Cell Treatments Attenuate Punctate and Dynamic Mechanical Allodynia in a Mouse Model of Sciatic Nerve Injury.Journal of Pain
Nerve injury-induced mechanical hyper-sensitivity, in particular stroking-induced dynamic allodynia, is highly debilitating and difficult to treat. Previous studies indicate that the immunosuppressive regulatory T (Treg) cells modulate the magnitude of punctate mechanical allodynia resulting from sciatic nerve injury. However, whether enhancing Treg-mediated suppression attenuates dynamic allodynia is not known. In the present study, we addressed this knowledge gap by treating mice with low-dose interleukin-2 (ld-IL2) injections or adoptive transfer of Treg cells.
Female Swiss Webster mice received daily injections of ld-IL2 (1 μg/mouse, intraperitoneally) either before or after unilateral spared nerve injury (SNI). Male C57BL/6J mice received adoptive transfer of 1 x 106 Treg cells 3 weeks post-SNI. The responses to punctate and dynamic mechanical stimuli on the hindpaw were monitored before and up to 4-6 weeks post-SNI. We also compared the distribution of Treg cells and CD3+ total T cells after SNI and/or ld-IL2 treatment.
Ld-IL2 pretreatment in female Swiss Webster mice completely blocked the development of SNI-induced dynamic mechanical allodynia and reduced the magnitude of punctate allodynia. Delayed ld-IL2 treatment in female mice significantly attenuated the morphine-resistant punctate and dynamic allodynia at 3-5 weeks post-SNI. Adoptive transfer of Treg cells to male C57BL/6J mice 3 weeks post-SNI effectively reversed the persistent punctate and dynamic allodynia, supporting that the effect of ld-IL2 is mediated through endogenous Treg cells, and is likely independent of mouse strain and sex. Neither ld-IL2 treatment nor Treg transfer affected the basal responses to punctate or brush stimuli. Ld-IL2 significantly increased the frequency of Treg cells among total CD3+ T cells in the injured sciatic nerves but not in the uninjured nerves or the dorsal root ganglia, suggesting the injured nerve as ld-IL2's site of action.
Collectively, results from the present study supports Treg as a cellular target and ld-IL2 as a potential therapeutic option for nerve injury-induced persistent punctate and dynamic mechanical allodynia.
Molecular and Electrophysiological Characterization of Dorsal Horn Neurons in a GlyT2-iCre-tdTomato Mouse Line.Journal of Pain
Spinal glycinergic neurons function as critical elements of a spinal gate for pain and itch. We have recently documented that spinal PKCγ+ neurons receive the feedforward inhibitory input driven by Aβ primary afferent. The glycinergic neurons control the excitability of PKCγ+ neurons and therefore gate mechanical allodynia. However, a dynamic or electrophysiological analysis of the synaptic drive on spinal glycinergic interneurons from primary afferent fibers is largely absent. The present study was aimed to analyze the synaptic dynamics between spinal glycinergic interneurons and primary afferents using a genetic labeled animal model.
The GlyT2-P2A-iCre mice were constructed by the CRISPR/Cas9 technology. The GlyT2-iCre-tdTomato mice were then generated by crossing the GlyT2-P2A-iCre mice with fluorescent reporter mice. Patch-clamp whole-cell recordings were used to analyze the dynamic synaptic inputs to glycinergic neurons in GlyT2-iCre-tdTomato mice. The distribution of GlyT2-tdTomato neurons in the spinal dorsal horn was examined by the immunohistochemistry method. The firing pattern and morphological features of GlyT2-tdTomato neurons were also examined by electrophysiological recordings and intracellular injection of biocitin.
The GlyT2-P2A-iCre and GlyT2-tdTomato mice were successfully constructed. GlyT2-tdTomato fluorescence was colocalized extensively with immunoreactivity of glycine, GlyT2 and Pax2 in somata, confirming the selective expression of the transgene in glycinergic neurons. GlyT2-tdTomato neurons were mainly distributed in spinal lamina IIi through IV. The firing pattern and morphological properties of GlyT2-tdTomato neurons met the features of tonic central or islet type of spinal inhibitory interneurons. The majority (72.1%) of the recorded GlyT2-tdTomato neurons received primary inputs from Aβ fibers.
The present study indicated that spinal GlyT2-positive glycinergic neurons mainly received primary afferent Aβ fiber inputs; the GlyT2-P2A-iCre and GlyT2-tdTomato mice provided a useful animal model to further investigate the function of the GlyT2+-PKCγ+ feedforward inhibitory circuit in both physiological and pathological conditions.
Pharmacological modulation of brain activation to non-noxious stimulation in a cynomolgus macaque model of peripheral nerve injury.Molecular Pain
In vivo neuroimaging could be utilized as a noninvasive tool for elaborating the CNS mechanism of chronic pain and for elaborating mechanisms of po...
Systemic gene expression profiles according to pain types in individuals with chronic spinal cord injury.Molecular Pain
Pain affects most individuals with traumatic spinal cord injury (SCI). Major pain types after SCI are neuropathic or nociceptive, often experienced...
The analgesic efficacy of liposomal bupivacaine compared with bupivacaine hydrochloride for the prevention of postoperative pain: a systematic review and meta-analysis with trial sequential analysis.Regional Anesthesia and Pain Medicine
Liposomal bupivacaine (LB) is a prolonged release formulation of conventional bupivacaine designed for prolonging local or peripheral regional single injection anesthesia. To this day, the benefit of the new substance on relevant end points is discussed controversial.
The objective was to determine whether there is a difference in postoperative pain scores and morphine consumption between patients treated with LB and bupivacaine hydrochloride in a systematic review and meta-analysis.
Randomized controlled trials (RCT) were identified in Embase, CENTRAL, MEDLINE and Web of Science up to May 2020. Risk of bias was assessed using Cochrane methodology. Primary end points were the mean pain score difference and the relative morphine equivalent (MEQ) consumption expressed as the ratio of means (ROM) 24 and 72 hours postoperatively.
23 RCTs including 1867 patients were eligible for meta-analysis. The mean pain score difference at 24 hours postoperatively was significantly lower in the LB group, at -0.37 (95% CI -0.56 to -0.19). The relative MEQ consumption after 24 hours was also significantly lower in the LB group, at 0.85 (0.82 to 0.89). At 72 hours, the pain score difference was not significant at -0.25 (-0.71 to 0.20) and the MEQ ratio was 0.85 (0.77 to 0.95).
The beneficial effect on pain scores and opioid consumption was small but not clinically relevant, despite statistical significance. The effect was stable among all studies, indicating that it is independent of the application modality.
Invasive placebos in research on peripheral nerve blocks: a follow-up study.Regional Anesthesia and Pain Medicine
The Serious Harm and Morbidity "SHAM" grading system has previously been proposed to categorize the risks associated with the use of invasive placebos in peripheral nerve block research. SHAM grades range from 0 (no potential complications, eg, using standard analgesia techniques as a comparator) through to 4 (risk of major complications, eg, performing a sub-Tenon's block and injecting normal saline). A study in 2011 found that 52% of studies of peripheral nerve blocks had SHAM grades of 3 or more.
We repeated the original study by allocating SHAM grades to randomized controlled studies of peripheral nerve blocks published in English over a 22-month period. Documentation was made of the number of study participants, age, number of controls, body region, adverse events due to invasive placebos and any discussion regarding the ethics of using invasive placebos. We compared the proportion of studies with SHAM grades of 3 or more with the original study.
In this current study, 114 studies fulfilled the inclusion criteria, 5 pediatric and 109 adult. The SHAM grade was ≥3 in 38 studies (33.3%), with 1494 patients in these control groups collectively. Several studies discussed their reasons for choosing a non-invasive placebo. No pediatric studies had a SHAM grade of ≥3.
The use of invasive placebos that may be associated with serious risks in peripheral nerve block research has decreased in contemporary peripheral nerve block research.
Neonatal and early childhood outcomes following maternal anesthesia for cesarean section: a population-based cohort study.Regional Anesthesia and Pain Medicine
The fetus is vulnerable to maternal drug exposure. We determined associations of exposure to spinal, epidural, or general anesthesia on neonatal and childhood development outcomes during the first 1000 days of life.
Population-based study of all singleton, cesarean livebirths of 24+0 to 43+6 weeks gestation between January 2007 and December 2016 in Scotland, stratified by urgency with follow-up to age 2 years. Models were adjusted for: maternal age, weight, ethnicity, socioeconomic status, smoking, drug-use, induction, parity, previous cesarean or abortion, pre-eclampsia, gestation, birth weight, and sex.
140 866 mothers underwent cesarean section (41.2% (57,971/140,866) elective, 58.8% (82,895/140,866) emergency) with general anesthesia used in 3.2% (1877/57,971) elective and 9.8% (8158/82,895) of emergency cases. In elective cases, general anesthesia versus spinal was associated with: neonatal resuscitation (crude event rate 16.2% vs 1.9% (adjusted RR 8.20, 95% CI 7.20 to 9.33), Apgar <7 at 5 min (4.6% vs 0.4% (adjRR 11.44, 95% CI 8.88 to 14.75)), and neonatal admission (8.6% vs 4.9% (adjRR 1.65, 95% CI 1.40 to 1.94)). Associations were similar in emergencies; resuscitation (32.2% vs 12.3% (adjRR 2.40, 95% CI 2.30 to 2.50)), Apgar <7 (12.6% vs 2.8% (adjRR 3.87, 95% CI 3.56 to 4.20), and admission (31.6% vs 19.9% (adjRR 1.20, 95% CI 1.15 to 1.25). There was a weak association between general anesthesia in emergency cases and having ≥1 concern noted in developmental assessment at 2 years (21.0% vs 16.5% (adjRR 1.08, 95% CI 1.01 to 1.16)).
General anesthesia for cesarean section, irrespective of urgency, is associated with neonatal resuscitation, low Apgar, and neonatal unit admission. Associations were strongest in non-urgent cases and at term. Further evaluation of long-term outcomes is warranted.
Chronic Pain: What Does It Mean? A Review on the Use of the Term Chronic Pain in Clinical Practice.Journal of Pain
Chronic pain is nowadays used as an umbrella term referring to a wide range of clinical conditions, such as fibromyalgia, migraine, or long-standin...
Prevalence of Fibromyalgia in Pharmacy Professionals and Students: A Cross-Sectional Study.Journal of Pain
The prevalence of fibromyalgia (FM) in pharmacy students and professionals is unknown. This study identifies the prevalence of FM in pharmacy students and professionals using three screening tools and factors associated with its development. Furthermore, this study assesses the level of agreement between the tools and the magnitude of the participants' responses to each item in the screening tools.
This was a cross-sectional survey conducted on members of the Saudi Pharmaceutical Society using an online questionnaire. The participants were asked to fill three questionnaires: the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ), Fibromyalgia Rapid Screening Tool (FiRST) and Fibromyalgia Survey Questionnaire (FSQ). Demographic data and factors affecting FM in pharmacy students and professionals were collected and analysed.
Two hundred ninety-three participants accessed the survey: most of them were Saudi (93.5%) and females (78.8%) with a mean (standard deviation) age of 29 (8) years. Furthermore, 52% of the participants had generalised body pain. The prevalence of FM using FiRST, LFESSQ Pain, LFESSQ with fatigue criteria and FSQ was 27.1%, 34.9%, 50.9% and 68.4%, respectively. Fleiss' kappa coefficient revealed fair agreement among all three screening tools (kappa = 0.350; p < 0.001). After adjusting for significant variables, the resulting adjusted odds ratio of developing FM was 4.86 in people working for 41-45 h weekly (95% confidence interval [CI], 1.32-17.84; p = 0.017), 5.16 in people who frequently wake up during sleep (95% CI, 1.85-14.40; p = 0.002) and 12.99 in people with sleep apnea or other sleeping disorders (95% CI, 2.07-81.68; p = 0.006).
FM was prevalent among pharmacy students and professionals and was much more than data reported on the general population or other healthcare workers. Traditional factors along with higher working hours were identified as significant variables.
P-Selectin Blockade in the Treatment of Painful Vaso-Occlusive Crises in Sickle Cell Disease: A Spotlight on Crizanlizumab.Journal of Pain
Microvascular vaso-occlusion driven pain crisis is the hallmark of sickle cell disease with profound morbidity and increased mortality. Selectins, ...
Antinociceptive Effect of Lodenafil Carbonate in Rodent Models of Inflammatory Pain and Spinal Nerve Ligation-Induced Neuropathic Pain.Journal of Pain
New therapeutic alternatives for pain relief include the use of phosphodiesterase-5 (PDE5) inhibitors, which could prevent the transmission of painful stimuli by neuron hyperpolarization via nitric oxide (NO)/cyclic 3',5'-guanosine monophosphate (cGMP) pathway. The present work investigated the antinociceptive activity of a new PDE5 inhibitor, lodenafil carbonate, in inflammatory and neuropathic pain models.
Although no effect was detected on neurogenic phase of formalin test in mice, oral administration of lodenafil carbonate dose-dependently reduced reactivity in the inflammatory phase (200.6 ± 39.1 to 81.9 ± 18.8 s at 10 μmol/kg, p= 0.0172) and this effect was totally blocked by NO synthase inhibitor, L-Nω-nitroarginine methyl ester (L-NAME). Lodenafil carbonate (10 μmol/kg p.o.) significantly reduced nociceptive response as demonstrated by increased paw withdrawal latency to thermal stimulus (from 6.8 ± 0.7 to 10.6 ± 1.3 s, p= 0.0006) and paw withdrawal threshold to compressive force (from 188.0 ± 14.0 to 252.5 ± 5.3 g, p<0.0001) in carrageenan-induced paw inflammation model. In a spinal nerve ligation-induced neuropathic pain, oral lodenafil carbonate (10 μmol/kg) also reversed thermal hyperalgesia and mechanical allodynia by increasing paw withdrawal latency from 17.9 ± 1.5 to 22.8 ± 1.9 s (p= 0.0062) and paw withdrawal threshold from 26.0 ± 2.8 to 41.4 ± 2.9 g (p= 0.0196). These effects were reinforced by the reduced GFAP (3.4 ± 0.5 to 1.4 ± 0.3%, p= 0.0253) and TNF-alpha (1.1 ± 0.1 to 0.4 ± 0.1%, p= 0.0111) stained area densities as detected by immunofluorescence in ipsilateral dorsal horns.
Lodenafil carbonate demonstrates important analgesic activity by promoting presynaptic hyperpolarization and preventing neuroplastic changes, which may perpetuate chronic pain, thus representing a potential treatment for neuropathic pain.
Transdermal Buprenorphine for Acute Pain in the Clinical Setting: A Narrative Review.Journal of Pain
Transdermal buprenorphine is indicated for chronic pain management, but as its role in the clinical management of acute pain is less clear, this na...