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The Journal of Headache and Pain Jan 2024Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which... (Review)
Review
BACKGROUND
Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways.
METHODS
A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review.
RESULTS
We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development.
CONCLUSIONS
Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.
Topics: Animals; Mechanotransduction, Cellular; Pain; Migraine Disorders; Nociception
PubMed: 38221631
DOI: 10.1186/s10194-023-01710-1 -
Headache May 2023To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology. (Review)
Review
OBJECTIVE
To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology.
BACKGROUND
The features of migraine attacks, including characteristics, duration, frequency, and prevalence, are sex-dependent with variability across a lifetime, indicating the involvement of the hypothalamus-pituitary-gonadal axis. Prolactin is a key regulator of this axis, and a new line of evidence implicates prolactin signaling in sex-related differences in pain perception.
METHODS
In this systematic review, we searched PubMed and EMBASE for the terms prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain, and trigeminal pain pathway to find preclinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.
RESULTS
Of a total of 15 preclinical articles selected, 11 were both ex vivo and in vivo, 3 were ex vivo, and 1 was an in vivo study. The main findings were that prolactin receptors are distributed in the trigeminal pain pathway, and prolactin induced migraine-like behavior in rodents. Moreover, prolactin signaling has a crucial role in calcitonin gene-related peptide (CGRP) release, a key molecule in migraine pathogenesis, and prolactin gene deletion attenuated CGRP-induced migraine-like behavior.
CONCLUSION
Preclinical data indicate a key role of prolactin and its receptors in mechanisms causing migraine. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify the influences of prolactin in migraine-attack initiation.
Topics: Humans; Calcitonin Gene-Related Peptide; Headache; Migraine Disorders; Pain; Prolactin; Animals; Mice; Rats
PubMed: 36752584
DOI: 10.1111/head.14412 -
Frontiers in Human Neuroscience 2023Deep brain stimulation (DBS) has shown promise in effectively treating chronic pain. This study aimed to assess the efficacy of DBS in this context.
BACKGROUND
Deep brain stimulation (DBS) has shown promise in effectively treating chronic pain. This study aimed to assess the efficacy of DBS in this context.
METHODS
We conducted a systematic literature search using PubMed, Scopus, and Web of Science, following the PRISMA guidelines. A well-constructed search strategy was utilized. Our literature search identified two groups of subjects: one group underwent DBS specifically for chronic pain treatment (DBS-P), while the second group received DBS for other indications (DBS-O), such as Parkinson's disease or dystonia, with pain perception investigated as a secondary outcome in this population. Meta-analysis was performed using R version 4.2.3 software. Heterogeneity was assessed using the tau^2 and I^2 indices, and Cochran's -test was conducted.
RESULTS
The analysis included 966 patients in 43 original research studies with chronic pain who underwent DBS (340 for DBS-P and 625 for DBS-O). Subgroup analysis revealed that DBS-P exhibited a significant effect on chronic pain relief, with a standardized mean difference (SMD) of 1.65 and a 95% confidence interval (CI) of [1.31; 2.00]. Significant heterogeneity was observed among the studies, with an I^2 value of 85.8%. However, no significant difference was found between DBS-P and DBS-O subgroups. Subgroup analyses based on study design, age, pain diseases, and brain targets demonstrated varying levels of evidence for the effectiveness of DBS across different subgroups. Additionally, meta-regression analyses showed no significant relationship between age or pain duration and DBS effectiveness for chronic pain.
CONCLUSION
These findings significantly contribute to the expanding body of knowledge regarding the utility of DBS in the management of chronic pain. The study underscores the importance of conducting further research to enhance treatment outcomes and elucidate patient-specific factors that are associated with treatment response.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=428442, identifier CRD42023428442.
PubMed: 38098761
DOI: 10.3389/fnhum.2023.1297894 -
The Cochrane Database of Systematic... Jun 2024Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are available to control postburn pruritus; however, it remains unclear how effective these are.
OBJECTIVES
To assess the effects of interventions for treating postburn pruritus in any care setting.
SEARCH METHODS
In September 2022, we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched clinical trials registries and scanned references of relevant publications to identify eligible trials. There were no restrictions with respect to language, publication date, or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that enrolled people with postburn pruritus to compare an intervention for postburn pruritus with any other intervention, placebo or sham intervention, or no intervention.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included 25 RCTs assessing 21 interventions with 1166 randomised participants. These 21 interventions can be grouped into six categories: neuromodulatory agents (such as doxepin, gabapentin, pregabalin, ondansetron), topical therapies (such as CQ-01 hydrogel, silicone gel, enalapril ointment, Provase moisturiser, beeswax and herbal oil cream), physical modalities (such as massage therapy, therapeutic touch, extracorporeal shock wave therapy, enhanced education about silicone gel sheeting), laser scar revision (pulsed dye laser, pulsed high-intensity laser, fractional CO2 laser), electrical stimulation (transcutaneous electrical nerve stimulation, transcranial direct current stimulation), and other therapies (cetirizine/cimetidine combination, lemon balm tea). Most RCTs were conducted at academic hospitals and were at a high risk of performance, attrition, and detection bias. While 24 out of 25 included studies reported change in burn-related pruritus, secondary outcomes such as cost-effectiveness, pain, patient perception, wound healing, and participant health-related quality of life were not reported or were reported incompletely. Neuromodulatory agents versus antihistamines or placebo There is low-certainty evidence that doxepin cream may reduce burn-related pruritus compared with oral antihistamine (mean difference (MD) -2.60 on a 0 to 10 visual analogue scale (VAS), 95% confidence interval (CI) -3.79 to -1.42; 2 studies, 49 participants). A change of 2 points represents a minimal clinically important difference (MCID). Due to very low-certainty evidence, it is uncertain whether doxepin cream impacts the incidence of somnolence as an adverse event compared to oral antihistamine (risk ratio (RR) 0.64, 95% CI 0.32 to 1.25; 1 study, 24 participants). No data were reported on pain in the included study. There is low-certainty evidence that gabapentin may reduce burn-related pruritus compared with cetirizine (MD -2.40 VAS, 95% CI -4.14 to -0.66; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that gabapentin reduces the incidence of somnolence compared to cetirizine (RR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants). No data were reported on pain in the included study. There is low-certainty evidence that pregabalin may result in a reduction in burn-related pruritus intensity compared with cetirizine with pheniramine maleate (MD -0.80 VAS, 95% CI -1.24 to -0.36; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that pregabalin reduces the incidence of somnolence compared to cetirizine (RR 0.04, 95% CI 0.00 to 0.69; 1 study, 40 participants). No data were reported on pain in the included study. There is moderate-certainty evidence that ondansetron probably results in a reduction in burn-related pruritus intensity compared with diphenhydramine (MD -0.76 on a 0 to 10 numeric analogue scale (NAS), 95% CI -1.50 to -0.02; 1 study, 38 participants). A change of 2 points represents a MCID. No data were reported on pain and adverse events in the included study. Topical therapies versus relevant comparators There is moderate-certainty evidence that enalapril ointment probably decreases mean burn-related pruritus compared with placebo control (MD -0.70 on a 0 to 4 scoring table for itching, 95% CI -1.04 to -0.36; 1 study, 60 participants). No data were reported on pain and adverse events in the included study. Physical modalities versus relevant comparators Compared with standard care, there is low-certainty evidence that massage may reduce burn-related pruritus (standardised mean difference (SMD) -0.86, 95% CI -1.45 to -0.27; 2 studies, 166 participants) and pain (SMD -1.32, 95% CI -1.66 to -0.98). These SMDs equate to a 4.60-point reduction in pruritus and a 3.74-point reduction in pain on a 10-point VAS. A change of 2 VAS points in itch represents a MCID. No data were reported on adverse events in the included studies. There is low-certainty evidence that extracorporeal shock wave therapy (ESWT) may reduce burn-related pruritus compared with sham stimulation (SMD -1.20, 95% CI -1.65 to -0.75; 2 studies, 91 participants). This equates to a 5.93-point reduction in pruritus on a 22-point 12-item Pruritus Severity Scale. There is low-certainty evidence that ESWT may reduce pain compared with sham stimulation (MD 2.96 on a 0 to 25 pressure pain threshold (PPT), 95% CI 1.76 to 4.16; 1 study, 45 participants). No data were reported on adverse events in the included studies. Laser scar revision versus untreated or placebo controls There is moderate-certainty evidence that pulsed high-intensity laser probably results in a reduction in burn-related pruritus intensity compared with placebo laser (MD -0.51 on a 0 to 1 Itch Severity Scale (ISS), 95% CI -0.64 to -0.38; 1 study, 49 participants). There is moderate-certainty evidence that pulsed high-intensity laser probably reduces pain compared with placebo laser (MD -3.23 VAS, 95% CI -5.41 to -1.05; 1 study, 49 participants). No data were reported on adverse events in the included studies.
AUTHORS' CONCLUSIONS
There is moderate to low-certainty evidence on the effects of 21 interventions. Most studies were small and at a high risk of bias related to blinding and incomplete outcome data. Where there is moderate-certainty evidence, practitioners should consider the applicability of the evidence for their patients.
Topics: Humans; Pruritus; Burns; Randomized Controlled Trials as Topic; Bias; Antipruritics
PubMed: 38837237
DOI: 10.1002/14651858.CD013468.pub2 -
Journal of Occupational Rehabilitation Jun 2021The main objective of this study is to update the evidence related to the effectiveness of exercise and ergonomic interventions in the perception of shoulder pain... (Meta-Analysis)
Meta-Analysis Review
The main objective of this study is to update the evidence related to the effectiveness of exercise and ergonomic interventions in the perception of shoulder pain intensity in workers considering the shoulder pain intensity and the minimum clinically important change in the analysis. The bibliographic search was conducted in seven databases (Cochrane, EMBASE, SciELO, PubMed, PEDro, Web of Science and Scopus) from March to April 2019. The study selection included randomized controlled trials (RCTs) involving workers with shoulder pain who underwent physical exercises, ergonomics, and combined interventions. To analyze the RCTs, the intensity of pain was divided into two subgroups < 3 and ≥ 3 (0-10 points scale). A total of 27 RCTs were included in the qualitative synthesis considering the perception scales of shoulder pain intensity and the PEDro scale score of assessment of RCTs quality and risk of bias. Within these, seven RCTs were included in the quantitative synthesis. The overall effectiveness of interventions was calculated using a meta-analysis method, and the associated measurement used as a mean difference. The meta-analysis revealed that exercise interventions in workers with shoulder pain > 3 presented a minimally clincially important difference (MCID), but with no difference in workers with pain < 3. The interventions with exercise in workers with pain ≥ 3 at baseline reported a beneficial effect in reducing shoulder pain intensity, and a MCID. However, there was no significant difference for workers with pain < 3 and the effects of ergonomic interventions are still uncertain to reduce shoulder pain in workers.
Topics: Ergonomics; Exercise; Humans; Shoulder Pain; Workplace
PubMed: 33006720
DOI: 10.1007/s10926-020-09927-6 -
Journal of Endocrinological... Oct 2022Acromegaly is a rare chronic disease characterized by systemic comorbidity and reduced quality of life. Although achieving biochemical control has always been the... (Review)
Review
PURPOSE
Acromegaly is a rare chronic disease characterized by systemic comorbidity and reduced quality of life. Although achieving biochemical control has always been the primary goal of acromegaly therapy, recent evidence has shown that the traditional assessment does not adequately capture the complexity of symptoms and patients' perception. These findings result in the need to improve a fast decision-making process of the clinician, who should not only take into account biochemical-instrumental criteria, but also patients' symptoms. With the aim of supporting the clinician in the diagnostic and therapeutic decision-making process several disease-specific tools have been developed. The aim of this review is to provide a description of the acromegaly-specific tools, presenting their main features, their application in daily practice, and their efficacy and utility.
METHODS
A systematic search of Medline/PubMed, ISI-Web of Knowledge, and Google Scholar databases was done.
RESULTS
Specific instruments and questionnaires have recently been developed to assist clinicians in the assessment of acromegaly. These are either Patient-Reported Outcome tools, such as Acromegaly Quality of Life Questionnaire (AcroQoL) and Pain Assessment Acromegaly Symptom Questionnaire (PASQ), or Clinician-Reported Outcome tools, such as ACROSCORE, SAGIT and Acromegaly Disease Activity Tool (ACRODAT). Such tools are extremely flexible and, therefore, have been widely adopted by endocrinologists and other professionals, so much so that they have also been included as recommendations in the 2018 international guidelines.
CONCLUSION
Questionnaires and tools are useful in the management of acromegaly patients. They help clinicians evaluate patients' symptoms and could assist in the evaluation of disease activity.
Topics: Acromegaly; Comorbidity; Databases, Factual; Humans; Quality of Life; Surveys and Questionnaires
PubMed: 35322391
DOI: 10.1007/s40618-022-01782-x -
Neuroscience and Biobehavioral Reviews Mar 2023Pain-induced gamma-band oscillations (GBOs) are one of the most promising biomarkers of the pain experience. Although GBOs reliably encode pain perception across... (Meta-Analysis)
Meta-Analysis Review
Pain-induced gamma-band oscillations (GBOs) are one of the most promising biomarkers of the pain experience. Although GBOs reliably encode pain perception across different individuals and species, considerable heterogeneity could be observed in the characteristics and functions of GBOs. However, such heterogeneity of GBOs and its underlying sources have rarely been detailed previously. Here, we conducted a systematic review and meta-analysis to characterize the temporal, frequential, and spatial characteristics of GBOs and summarize the functional significance of distinct GBOs. We found that GBO heterogeneity was mainly related to pain types, with a higher frequency (∼66 Hz) GBOs at the sensorimotor cortex elicited by phasic pain and a lower frequency (∼55 Hz) GBOs at the prefrontal cortex associated with tonic and chronic pains. Positive correlations between GBO magnitudes and pain intensity were observed in healthy participants. Notably, the characteristics and functions of GBOs seemed to be phylogenetically conserved across humans and rodents. Altogether, we provided a comprehensive description of heterogeneous GBOs in pain and nociception, laying the foundation for clinical applications of GBOs.
Topics: Animals; Humans; Nociception; Rodentia; Electroencephalography; Pain Perception; Chronic Pain
PubMed: 36682424
DOI: 10.1016/j.neubiorev.2023.105062 -
Frontiers in Pain Research (Lausanne,... 2022The anesthetic management of fetal operative procedures (FOP) is a highly debated topic. Literature on fetal pain perception and response to external stimuli is rapidly... (Review)
Review
OBJECTIVE
The anesthetic management of fetal operative procedures (FOP) is a highly debated topic. Literature on fetal pain perception and response to external stimuli is rapidly expanding. Nonetheless, there is no consensus on the fetal consciousness nor on the instruments to measure pain levels. As a result, no guidelines or clinical recommendations on anesthesia modality during FOP are available. This systematic literature review aimed to collect the available knowledge on the most common fetal interventions, and summarize the reported outcomes for each anesthetic approach. Additional aim was to provide an overall evaluation of the most commonly used anesthetic agents.
METHODS
Two systematic literature searches were performed in Embase, Medline, Web of Science Core Collection and Cochrane Central Register of Controlled Trials up to December 2021. To best cover the available evidence, one literature search was mostly focused on fetal surgical procedures; while anesthesia during FOP was the main target for the second search. The following fetal procedures were included: fetal transfusion, laser ablation of placental anastomosis, twin-reversed arterial perfusion treatment, fetoscopic endoluminal tracheal occlusion, thoraco-amniotic shunt, vesico-amniotic shunt, myelomeningocele repair, resection of sacrococcygeal teratoma, ligation of amniotic bands, balloon valvuloplasty/septoplasty, ex-utero intrapartum treatment, and ovarian cyst resection/aspiration. Yielded articles were screened against the same inclusion criteria. Studies reporting anesthesia details and procedures' outcomes were considered. Descriptive statistical analysis was performed and findings were reported in a narrative manner.
RESULTS
The literature searches yielded 1,679 articles, with 429 being selected for full-text evaluation. A total of 168 articles were included. Overall, no significant differences were found among procedures performed under maternal anesthesia or maternal-fetal anesthesia. Procedures requiring invasive fetal manipulation resulted to be more effective when performed under maternal anesthesia only. Based on the available data, a wide range of anesthetic agents are currently deployed and no consistency has been found neither between centers nor procedures.
CONCLUSIONS
This systematic review shows great variance in the anesthetic management during FOP. Further studies, systematically reporting intraoperative fetal monitoring and fetal hormonal responses to external stimuli, are necessary to identify the best anesthetic approach. Additional investigations on pain pathways and fetal pain perception are advisable.
PubMed: 36246050
DOI: 10.3389/fpain.2022.935427 -
Journal of Pain and Symptom Management Jan 2022The Dyspnoea-12 (D-12) and Multidimensional Dyspnea Profile (MDP) were specifically developed for assessment of multiple sensations of breathlessness. (Review)
Review
CONTEXT
The Dyspnoea-12 (D-12) and Multidimensional Dyspnea Profile (MDP) were specifically developed for assessment of multiple sensations of breathlessness.
OBJECTIVES
This systematic review aimed to identify the use and measurement properties of the D-12 and MDP across populations, settings and languages.
METHODS
Electronic databases were searched for primary studies (2008-2020) reporting use of the D-12 or MDP in adults. Two independent reviewers completed screening and data extraction. Study and participant characteristics, instrument use, reported scores and minimal clinical important differences (MCID) were evaluated. Data on internal consistency (Cronbach's α) and test-retest reliability (intraclass correlation coefficient, ICC) were pooled using random effects models between settings and languages.
RESULTS
A total 75 publications reported use of D-12 (n = 35), MDP (n = 37) or both (n = 3), reflecting 16 chronic conditions. Synthesis confirmed two factor structure, internal consistency (Cronbach's α mean, 95% CI: D-12 Total = 0.93, 0.91-0.94; MDP Immediate Perception [IP] = 0.88, 0.85-0.90; MDP Emotional Response [ER] = 0.86, 0.82-0.89) and 14 day test-rest reliability (ICC: D-12 Total = 0.91, 0.88-0.94; MDP IP = 0.85, 0.70-0.93; MDP ER = 0.84, 0.73-0.90) across settings and languages. MCID estimates for clinical interventions ranged between -3 and -6 points (D-12 Total) with small variability in scores over 2 weeks (D-12 Total 2.8 (95% CI: 2.0 to 3.7), MDP-A1 0.8 (0.6 to 1.1) and six months (D-12 Total 2.9 (2.0 to 3.7), MDP-A1 0.8 (0.6 to 1.1)).
CONCLUSION
D-12 and MDP are widely used, reliable, valid and responsive across various chronic conditions, settings and languages, and could be considered standard instruments for measuring dimensions of breathlessness in international trials.
Topics: Adult; Dyspnea; Emotions; Humans; Language; Psychometrics; Reproducibility of Results; Surveys and Questionnaires
PubMed: 34273524
DOI: 10.1016/j.jpainsymman.2021.06.023 -
Clinical Oral Investigations Dec 2023To assess whether in animals or patients with ≥ 1 tooth extracted, hyaluronic acid (HyA) application results in superior healing and/or improved complication... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess whether in animals or patients with ≥ 1 tooth extracted, hyaluronic acid (HyA) application results in superior healing and/or improved complication management compared to any other treatment or no treatment.
MATERIALS AND METHODS
Three databases were searched until April 2022. The most relevant eligibility criteria were (1) local application of HyA as adjunct to tooth extraction or as treatment of alveolar osteitis, and (2) reporting of clinical, radiographic, histological, or patient-reported data. New bone formation and/or quality were considered main outcome parameters in preclinical studies, while pain, swelling, and trismus were defined as main outcome parameters in clinical studies.
RESULTS
Five preclinical and 22 clinical studies (1062 patients at final evaluation) were included. In preclinical trials, HyA was applied into the extraction socket. Although a positive effect of HyA was seen in all individual studies on bone formation, this effect was not confirmed by meta-analysis. In clinical studies, HyA was applied into the extraction socket or used as spray or mouthwash. HyA application after non-surgical extraction of normally erupted teeth may have a positive effect on soft tissue healing. Based on meta-analyses, HyA application after surgical removal of lower third molars (LM3) resulted in significant reduction in pain perception 7 days postoperatively compared to either no additional wound manipulation or the application of a placebo/carrier. Early post-operative pain, trismus, and extent of swelling were unaffected.
CONCLUSIONS
HyA application may have a positive effect in pain reduction after LM3 removal, but not after extraction of normally erupted teeth.
CLINICAL RELEVANCE
HyA application may have a positive effect in pain reduction after surgical LM3 removal, but it does not seem to have any impact on other complications or after extraction of normally erupted teeth. Furthermore, it seems not to reduce post-extraction alveolar ridge modeling, even though preclinical studies show enhanced bone formation.
Topics: Humans; Animals; Tooth Socket; Hyaluronic Acid; Trismus; Dry Socket; Tooth Extraction; Molar, Third; Pain
PubMed: 37963982
DOI: 10.1007/s00784-023-05227-4