Lighting the shades of hidden pain:a role for spinal cord neurons and microglia in vestibulodynia

Vulvodynia,a chronic pain disorder affecting the vulvar region,represents a significant challenge in both diagnosis and treatment within the field of women’s health.This condition is characterized by chronic pain that significantly affects the quality of life of afflicted women.The present perspective paper examines the role of spinal sensitization and microglial activation in vulvodynia.

Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.

Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

Application of virtual reality technology improves the functionality of brain networks in individuals experiencing pain

Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.

Trends in oxycodone and oxycodone-containing analgesics administration for back pain in emergency departments in the USA(2007–2018)

BACKGROUND:To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments(EDs) in the USA from 2007 to 2018.METHODS:Data were gathered from the National Hospital Ambulatory Medical Care Survey(NHAMCS) from 2007 to 2018.The study population included individuals of all ages presenting to USA EDs.The NHAMCS reasons for visit and oxycodone drug ID codes were used to isolate patients with back pain.The main outcome was the proportion of oxycodone and oxycodone-containing analgesics prescribed for back pain in the EDs over the specified time period.RESULTS:There was a relative decrease in the overall administration of oxycodone for back pain in the EDs by 62.3% from 2007(244,000 visits) to 2018(92,000 visits).The proportion of ED patients prescribed with oxycodone-containing analgesics for back pain increased among patients aged 45 years and older(from 43.8% to 57.6%),female patients(from 54.5% to 62.0%),black patients(from 22.5% to 30.4%),and Hispanic/Latino patients(from 9.4% to 19.6%).Oxycodone/acetaminophen was most prescribed and accounted for 90.2% of all oxycodone-containing analgesics in 2007,with a decrease to 68.5% in 2018.Pure oxycodone was the second most prescribed medication,accounting for 6.1% in 2007 and 31.5% in 2018.CONCLUSION:The overall number of oxycodone-containing analgesics decreased significantly from 2007 to 2018.However,that number trended upward in 45-year-old and older,female,black,or Hispanic/Latino patients from 2007 to 2018.The total amount of pure oxycodone increased significantly from 2007 to 2008.

Protocol for lower back pain management: Insights from the French healthcare system

In this editorial we comment on the article published in a recent issue of the World Journal of Clinical Cases.This article described a novel ultrasound-guided lateral recess block approach in treating a patient with lateral recess stenosis.The impact of spinal pain-related disability extends significantly,causing substantial human suffering and medical costs.Each county has its preferred treatment strategies for spinal pain.Here,we explore the lower back pain(LBP)treatment algorithm recommended in France.The treatment algorithm for LBP recommended by the French National Authority for Health emphasizes early patient activity and minimal medication use.It encourages the continuation of daily activities,limits excessive medication and spinal injections,and incorporates psychological assessments and non-pharmacological therapies for chronic cases.However,the algorithm may not aggressively address acute pain in the early stages,potentially delaying relief and increasing the risk of chronicity.Additionally,the recommended infiltrations primarily involve caudal epidural steroid injections,with limited consideration for other injection procedures,such as transforaminal or interlaminar epidural steroid injections.The fixed follow-up timeline may not accommodate patients who do not respond to initial treatment or experience intense pain,potentially delaying the exploration of alternative therapies.Despite these limitations,understanding the strengths and weaknesses of the French approach could inform adaptations in LBP treatment strategies globally,potentially enhancing patient outcomes and satisfaction across diverse healthcare systems.

Treating acute low back pain with acupuncture:A randomized controlled study protocol to compare the effectiveness between distal and local acupoints

Objective:To compare the efficacy of using“distal acupoints only”vs.“local acupoints mainly combined with distal acupoints”in cases of acute low back pain(ALBP).Methods: A total of 102 eligible patients aged 18–65 years with ALBP lasting less than 6 weeks will be randomized in a 1:1 ratio to the distal acupoints only group(DPOG)and the local acupoints mainly combined with the distal acupoints group(LPMG).During a 4-week treatment period,patients in the DPOG will receive acupuncture at distal acupoints only(Houxi[SI 3]and Yaotongxue[EX-UE 7])twice a week,while those in the LPMG group will receive acupuncture at local acupoints(mainly Shenshu[BL 23]and Dachangshu[BL 25])combined with distal points(Weizhong[BL 40]).The patients in both groups will be evaluated at every session of treatment,and the follow-up will be performed for 3 months.The primary outcome measure will be the change in ALBP intensity,assessed using visual analogue scale scores before and after treatment.The secondary outcome measure will be the evaluation of functional disability using the Oswestry Disability Index.Discussion: This study compares the DPOG and LPMG to explore the feasibility of the DPOG in the treatment of ALBP.

Prevalence and Factors Associated with Chronic Low Back Pain in the Mining Sector in Burkina Faso

Introduction: Low back pain is nowadays a real public health problem in companies. The objective of the study was to determine the prevalence and factors associated with chronic low back pain among workers of a mining company in Burkina Faso. Material and Methods: This was a descriptive and analytical cross-sectional study with a retrospective collection that took place from August 1, 2021 to March 16, 2022 in a gold mine in Burkina Faso. It focused on mine workers who participated in the 2019 annual medical visit. Results: Out of a total workforce of 880 workers who took part in the annual medical visit in 2019, 165 had chronic common low back pain, i.e. a prevalence of 18.75%. The average age of low back pain workers was 37.21 ± 7.5 years. Among the workers suffering from low back pain, 62 (37.58%) held the position of machine operator. Clinically, mechanical pain was found in 113 low back pain workers (76%) and twenty-nine (17.58%) had radicular pain. Standard radiography of the lumbar spine was abnormal in 129 workers (78.18%. In the univariate analysis, the factors associated with the pathology were sex, level of study, work station and seniority in the position. After a logistic regression, the factors associated with its occurrence were whole-body vibration (Fisher’s test = 12.7541;P = 0.000), male sex (Fisher’s test = 8.363;P = 0.004), and seniority for 4 to 5 years (Chi2 = 4.0234;p = 0.046). Conclusion: The study reveals the existence of chronic low back pain cases among the workers of the mining company. There is a predominance of the pathology in men, workers exposed to vibrations and those with a seniority of 4 to 5 years. It is necessary to establish a policy of prevention of low back pain for the benefit of workers, in particular those exposed to vibrations.

A Study on the Effect of Exercise Intervention on Function and Pain in Patients with Low Back Pain

Lower back pain(LBP)has a relatively high incidence across various age groups,characterized by discomfort in the lumbosacral and iliosacral regions above the gluteal striatum and within the region below the costal margins.Some patients also experience varying degrees of leg pain,with many experiencing prolonged and recurrent symptoms.International consensus confirms that exercise intervention is an effective treatment method for lower back pain,offering safe and efficient physical therapy.Extensive practical experience suggests that Pilates exercises can effectively regulate the strength of muscle tissue in the peripheral region of the spine,improve muscle endurance,and alleviate low back pain caused by muscular factors.This study analyzes the effects of exercise intervention on the function and pain of patients with lower back pain.It explores various exercise modalities,utilizes SPSS26 statistics to gather data,and draws conclusions with the aim of providing theoretical references for exercise interventions in patients with lower back pain.

Comparing role of ATP between acute pain in neuromyelitis optica spectrum disorder and peripheral neuropathic pain

In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.

Investigating epithelial-neuronal signaling contribution in visceral pain through colon organoid-dorsal root ganglion neuron co-cultures

Abdominal pain is a common symptom associated with irritable bowel syndrome and inflammatory bowel diseases(IBDs),affecting about 20%of the global population(Grundy et al.,2019).Current pain therapies are poorly effective on visceral pain of intestinal origin and present several side effects,hence the need to identify novel molecular and cellular targets for drug development.

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

High-risk factors for delirium in severely ill patients and the application of emotional nursing combined with pain nursing

BACKGROUND Delirium is a neuropsychiatric syndrome characterized by acute disturbances of consciousness with rapid onset,rapid progression,obvious fluctuations,and preventable,reversible,and other characteristics.Patients with delirium in the intensive care unit(ICU)are often missed or misdiagnosed and do not receive adequate attention.AIM To analyze the risk factors for delirium in ICU patients and explore the applica-tion of emotional nursing with pain nursing in the management of delirium.METHODS General data of 301 critically ill patients were retrospectively collected,including histories(cardiovascular and cerebrovascular diseases,hypertension,smoking,alcoholism,and diabetes),age,sex,diagnosis,whether surgery was performed,and patient origin(emergency/clinic).Additionally,the duration of sedation,Richmond Agitation Sedation Scale score,combined emotional and pain care,ven-tilator use duration,vasoactive drug use,drainage tube retention,ICU stay du-ration,C-reactive protein,procalcitonin,white blood cell count,body tempe-rature,Acute Physiology and Chronic Health Evaluation II(APACHE II)score,and Sequential Organ Failure Assessment score were recorded within 24 h after ICU admission.Patients were assessed for delirium according to confusion assessment method for the ICU,and univariate and multivariate logistic regre-ssion analyses were performed to identify the risk factors for delirium in the patients.RESULTS Univariate logistic regression analysis was performed on the 24 potential risk factors associated with delirium in ICU patients.The results showed that 16 risk factors were closely related to delirium,including combined emotional and pain care,history of diabetes,and patient origin.Multivariate logistic regression analysis revealed that no combined emotional and pain care,history of diabetes,emergency source,surgery,long stay in the ICU,smoking history,and high APACHE II score were independent risk factors for de-lirium in ICU patients.CONCLUSION Patients with diabetes and/or smoking history,postoperative patients,patients with a high APACHE II score,and those with emergency ICU admission need emotional and pain care,flexible visiting modes,and early intervention to reduce delirium incidence.

Phrenic nerve block: the key to managing acute biliary pain?

Over the past two decades,the USA has witnessed a steep rise in the incidence of acute cholecystitis(AC),[1]even among children,[2]with over 200,000 cases annually.[3]Patients with AC often present to the emergency department(ED)experiencing severe distress,with most describing their pain level as“intolerable.”[4]Furthermore,there is usually a considerable delay before surgery,with a median time from diagnosis of AC to surgery of 28.5 h,[5]and a substantial percentage of patients wait as long as 10 d.[6]Prolonged delays before surgery lead to increased opioid use,which is associated with extended hospital stays and higher rates of readmission after cholecystectomy.[7]Furthermore,opioids can lead to vomiting,respiratory depression,delirium,and ultimately addiction.[8]We propose a novel regional anesthesia technique for managing AC:right phrenic nerve blockade.This method could offer improved pain control and a more favorable risk profile in selected patients when compared to current ED practices.

Differences between the healthcare systems of Quebec and France for the treatment of pain due to spinal disorders

In Quebec,Canada,the public healthcare system offers free medical services.However,patients with spinal pain often encounter long waiting times for specialist appointments and limited physiotherapy coverage.In contrast,private clinics provide expedited care but are relatively scarce and entail out-of-pocket expenses.Once a patient with pain caused by a spinal disorder meets a pain medicine specialist,spinal intervention is quickly performed when indicated,and patients are provided lifestyle advice.Transforaminal epidural steroid injections are frequently administered to patients with radicular pain,and steroid injections are administered on a facet joint to control low back or neck pain.Additionally,medial branch blocks are performed prior to thermocoagulation.France’s universal healthcare system ensures accessibility at controlled costs.It emphasizes physical activity and provides free physical therapy services.However,certain interventions,such as transforaminal and interlaminar epidural injections,are not routinely used in France owing to limited therapeutic efficacy and safety concerns.This underutilization may be a potential cause of chronic pain for many patients.By examining the differences,strengths,and weaknesses of these two systems,valuable insights can be gained for the enhancement of global spinal pain management strategies,ultimately leading to improved patient outcomes and satisfaction.

Pain perception enhancement in consecutive secondeye phacoemulsification cataract surgeries under topical anesthesia

Cataract is the main cause of visual impairment and blindness worldwide while the only effective cure for cataract is still surgery.Consecutive phacoemulsification under topical anesthesia has been the routine procedure for cataract surgery.However,patients often grumbled that they felt more painful during the second-eye surgery compared to the first-eye surgery.The intraoperative pain experience has negative influence on satisfaction and willingness for second-eye cataract surgery of patients with bilateral cataracts.Intraoperative ocular pain is a complicated process induced by the nociceptors activation in the peripheral nervous system.Immunological,neuropsychological,and pharmacological factors work together in the enhancement of intraoperative pain.Accumulating published literatures have focused on the pain enhancement during the secondeye phacoemulsification surgeries.In this review,we searched PubMed database for articles associated with pain perception differences between consecutive cataract surgeries published up to Feb.1,2024.We summarized the recent research progress in mechanisms and interventions for pain perception enhancement in consecutive secondeye phacoemulsification cataract surgeries.This review aimed to provide novel insights into strategies for improving patients’intraoperative experience in second-eye cataract surgeries.

Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

Use of artificial intelligence in the field of pain medicine

In this editorial we comment on the article“Potential and limitations of ChatGPT and generative artificial intelligence in medial safety education”published in the recent issue of the World Journal of Clinical Cases.This article described the usefulness of artificial intelligence(AI)in medial safety education.Herein,we focus specifically on the use of AI in the field of pain medicine.AI technology has emerged as a powerful tool,and is expected to play an important role in the healthcare sector and significantly contribute to pain medicine as further developments are made.AI may have several applications in pain medicine.First,AI can assist in selecting testing methods to identify causes of pain and improve diagnostic accuracy.Entry of a patient’s symptoms into the algorithm can prompt it to suggest necessary tests and possible diagnoses.Based on the latest medical information and recent research results,AI can support doctors in making accurate diagnoses and setting up an effective treatment plan.Second,AI assists in interpreting medical images.For neural and musculoskeletal disorders,imaging tests are of vital importance.AI can analyze a variety of imaging data,including that from radiography,computed tomography,and magnetic resonance imaging,to identify specific patterns,allowing quick and accurate image interpretation.Third,AI can predict the outcomes of pain treatments,contributing to setting up the optimal treatment plan.By predicting individual patient responses to treatment,AI algorithms can assist doctors in establishing a treatment plan tailored to each patient,further enhancing treatment effectiveness.For efficient utilization of AI in the pain medicine field,it is crucial to enhance the accuracy of AI decision-making by using more medical data,while issues related to the protection of patient personal information and responsibility for AI decisions will have to be addressed.In the future,AI technology is expected to be innovatively applied in the field of pain medicine.The advancement of AI is anticipated to have a positive impact on the entire medical field by providing patients with accurate and effective medical services.

Chronic venous insufficiency, could it be one of the missing pieces in the puzzle of treating pain?

Pain is a common complaint among patients seeking medical care.If left un-treated,pain can become chronic,significantly affecting patients’quality of life.An accurate diagnosis of the underlying cause of pain is crucial for effective treatment.Chronic venous insufficiency(CVI)is frequently overlooked by pain physicians.Moreover,many pain physicians lack sufficient knowledge about CVI.CVI is a common condition resulting from malfunctioning or damaged valves in lower limb veins.Symptoms of CVI,ranging from mild to severe,include pain,heaviness,fatigue,itching,swelling,skin color changes,and ulcers in the lower limbs.Recently,it has become more widely known that these symptoms can be attributed to CVI.Even slight or mild CVI can cause related symptoms.Pain physicians primarily consider neuromusculoskeletal disorders when assessing patients with leg pain,and often neglect the possibility of CVI.In clinical practice,when pain physicians encounter patients with unresolved leg pain,they must assess whether the patients exhibit symptoms of CVI and conduct tests to differ-entiate CVI from other potential causes.