重型创伤性脑损伤去骨瓣减压应用改良Paine点穿刺监测脑室内颅内压的优势

目的探讨重型创伤性脑损伤(TBI)开颅去骨瓣减压术(DC)中应用改良Paine点穿刺行脑室内颅内压(ICP)监测探头置入的优势。方法回顾性分析2020年4月-2022年4月嘉兴市第二医院收治的48例重型TBI患者的临床资料。所有患者均行DC联合脑室内ICP监护术,按照ICP监测术式的不同,分为观察组(23例)与对照组(25例),其中观察组行DC切口内改良Paine点穿刺脑室内ICP监测探头置入术,对照组行传统DC对侧切口颅骨钻孔经Kocher点脑室内ICP监测探头置入术。比较两组术前一般资料、手术用时、术后甘露醇使用剂量及持续时间、ICP监测持续时间、术后再出血率、颅内感染率、术后3个月时格拉斯哥预后评分(GOS)。结果两组一般资料、甘露醇使用剂量、甘露醇持续时间和ICP监测持续时间比较差异均无统计学意义(P>0.05);观察组手术用时、术后再出血率、颅内感染率明显少于或低于对照组(P<0.05);两组术后3个月GOS评分比较差异无统计学意义(P>0.05)。结论相较传统的DC对侧切口颅骨钻孔经Kocher点行脑室内ICP监测探头置入术,重型脑外伤DC术中通过切口内改良Paine点穿刺行脑室内ICP监测探头置入术可缩短手术用时,降低术后再出血率、颅内感染率。

Effect of ankle versus thigh tourniquets on post-operative pain in foot and ankle surgery

BACKGROUND Tourniquets are commonly used in elective extremity orthopaedic surgery to reduce blood loss,improve visualization in the surgical field,and to potentially reduce surgical time.There is a lack of consensus in existing guidelines regarding the optimal tourniquet pressure,placement site,and duration of use.There is a paucity of data on the relationship between the site of a tourniquet and postoperative pain in foot and ankle surgery.AIM To explore the relationship between tourniquet site and intensity of post-operative pain scores in patients undergoing elective foot and ankle surgery.METHODS Retrospective analysis of prospectively collected data on 201 patients who underwent foot and ankle surgery in a single institution was undertaken.Intraoperative tourniquet duration,tourniquet pressure and site,and postoperative pain scores using Visual Analogue Score were collected in immediate recovery,at six hours and at 24 h post-op.Scatter plots were used to analyse the data and to assess for the statistical correlation between tourniquet pressure,duration,site,and pain scores using Pearson correlation coefficient.RESULTS All patients who underwent foot and ankle surgery had tourniquet pressure of 250 mmHg for ankle tourniquet and 300 mmHg for thigh.There was no correlation between the site of the tourniquet and pain scores in recovery,at six hours and after 24 h.There was a weak correlation between tourniquet time and Visual Analogue Score immediately post-op(r=0.14,P=0.04)but not at six or 24 h post-operatively.CONCLUSION This study shows that there was no statistically significant correlation between tourniquet pressure,site and postop pain in patients undergoing foot and ankle surgery.The choice of using a tourniquet is based on the surgeon's preference,with the goal of minimizing the duration of its application at the operative site.

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.

Rehabilitation care for pain in elderly knee replacement patients

BACKGROUND Total knee arthroplasty(TKA)is recognized as the most effective surgical intervention for relieving pain and improving joint mobility and deformity in patients with knee osteoarthritis and other synovial diseases.The application of accelerated postoperative rehabilitation(enhanced recovery after surgery)has demonstrated its efficacy in improving patient outcomes,and early postoperative joint function exercise has become a key prognostic factor in knee replacement.The unexpected appearance of limb pain and swelling hindered the patient’s tendency for early mobilization,leading in prolonged hospitalization,delayed functional recovery and negative psychological responses.A retrospective analysis was conducted on a cohort of 116 patients who under-went TKA at our hospital between July 2019 and July 2021.The patients were divided into two groups:A control group(n=58)receiving programmatic nur-sing,and an observed group(n=58)receiving programmed nursing combined with a collaborative nursing model.A pain management team consisting of attending physicians,head nurses,and responsible nurses was established.Outcome measures included visual analogue scale(VAS)scores,activities of daily living(ADL)scale scores,and functional scores.The ADL scores of patients in both groups exhibited a continuous increase.However,there was no statistically significant difference in the ADL scores between the two groups at 48 h and the 7th d post-surgery(P>0.05).Upon reexamination at the 3rd mo,the observation group demonstrated higher ADL scores compared to the control group(67.48±14.69 vs 59.40±16.06,P<0.05).The VAS scores of both groups significantly decreased,with no significant difference observed between the groups at each time point(P>0.05).The functional status of patients in both groups exhibited a gradual increase prior to intervention and at the 1st,2nd,and 3rd month following discharge(P<0.05).There was no statistically significant difference in knee joint function scores between the two groups at the 1st month after discharge(47.52 vs 45.81,P>0.05).However,the knee joint function scores of patients in the observation group were significantly higher than those in the control group at the 2nd(59.38 vs 53.19,P<0.05)and 3rd month(71.92 vs 64.34,P<0.05)following discharge.CONCLUSION The utilization of programmed pain nursing in conjunction with collaborative nursing for out-of-hospital care of TKA patients has demonstrated favorable outcomes,encompassing pain reduction,enhanced prognosis,and improved nursing quality for patients.

Relationship between Kawasaki disease and abdominal pain

This editorial presents an analysis of an article recently published in the World Journal of Clinical Cases.Kawasaki disease(KD)is a well-known pediatric vasculitis characterized by fever,rash,conjunctivitis,oral mucosal changes,and swelling of the extremities.This editorial aims to delve into the intricate relationship between KD and abdominal pain,drawing insights from recent research findings to provide a comprehensive understanding and potential avenues for future investigation.

Meta-analysis of factors influencing anterior knee pain after total knee arthroplasty

BACKGROUND Total knee arthroplasty(TKA)is a mature procedure recommended for correcting knee osteoarthritis deformity,relieving pain,and restoring normal biomechanics.Although TKA is a successful and cost-effective procedure,patient dissatisfaction is as high as 50%.Knee pain after TKA is a significant cause of patient dissatisfaction;the most common location for residual pain is the anterior region.Between 4%and 40%of patients have anterior knee pain(AKP).AIM To investigate the effect of various TKA procedures on postoperative AKP.METHODS We searched PubMed,EMBASE,and Cochrane from January 2000 to September 2022.Randomized controlled trials with one intervention in the experimental group and no corresponding intervention(or other interventions)in the control group were collected.Two researchers independently read the title and abstract of the studies,preliminarily screened the articles,and read the full text in detail according to the selection criteria.Conflicts were resolved by consultation with a third researcher.And relevant data from the included studies were extracted and analyzed using Review Manager 5.4 software.RESULTS There were 25 randomized controlled trials;13 were comparative studies with or without patellar resurfacing.The meta-analysis showed no significant difference between the experimental and control groups(P=0.61).Six studies were comparative studies of circumpatellar denervation vs non-denervation,divided into three subgroups for meta-analysis.The two-subgroup meta-analysis showed no significant difference between the experimental and the control groups(P=0.31,P=0.50).One subgroup meta-analysis showed a significant difference between the experimental and control groups(P=0.001).Two studies compared fixed-bearing TKA and mobile-bearing TKA;the results meta-analysis showed no significant difference between the experimental and control groups(P=0.630).Two studies compared lateral retinacular release vs non-release;the meta-analysis showed a significant difference between the experimental and control groups(P=0.002);two other studies compared other factors.CONCLUSION Patellar resurfacing,mobile-bearing TKA,and fixed-bearing TKA do not reduce the incidence of AKP.Lateral retinacular release can reduce AKP;however,whether circumpatellar denervation can reduce AKP is controversial.

Effect of information-motivation-behavioral skills model based perioperative nursing on pain in patients with gallstones

BACKGROUND The incidence of cholecystolithiasis is on the rise.Use of information,motivation,and behavioral skills can play a positive role in promoting changes in individual health behaviors.However,reports on the effects of information-motivationbehavioral(IMB)skills model based high-quality nursing as a perioperative nursing intervention for patients with gallstones are nonexistent.AIM To explore the application of IMB skills model based high-quality nursing in patients with gallstones.METHODS Two hundred and sixteen patients with cholecystolithiasis treated at our hospital from January 2022 to January 2023 were enrolled and divided into a control,highquality,and combined nursing groups,with 72 patients in each group.The control,high-quality,and combination groups received conventional,high-quality,and IMB skills model based perioperative nursing services,respectively.Differences in clinical indicators,stress levels,degree of pain,emotional state,and quality of life were observed,and complications and nursing satisfaction among the three groups were evaluated.RESULTS After nursing,the time to recovery of gastrointestinal function in the high-quality and combined nursing groups was significantly shorter than that of the control group,with the recovery of gastrointestinal function being the fastest in the combined nursing group(P<0.05).After nursing intervention,cortisol and norepinephrine levels in the high-quality and combined nursing groups were closer to normal than those of the control group 24 h after surgery,with the combined nursing group having the closest to normal levels(P<0.05).After 3 and 7 d of intervention,the patients’pain significantly improved,which was more prominent in the highquality and combination groups.Meanwhile,the pain score in the combination group was significantly lower than those of the control and high-quality nursing groups(P<0.05).After nursing intervention,the emotional states of all patients improved,and the scores of patients in the combination group were significantly lower than those of the control and high-quality nursing groups.The quality of life of patients in the high-quality and combined nursing groups significantly improved after nursing intervention compared to that of the control group,with the combined nursing group having the highest quality of life score.After intervention,the incidence of complications in the high-quality and combination groups was significantly lower than that of the control group(P<0.05),but the difference between the combination and high-quality nursing groups was not significant.Nursing satisfaction of patients in the high-quality and combination groups was significantly higher than that of the control group,with the nursing satisfaction being the highest in the combination group(P<0.05).CONCLUSION IMB skills model based nursing can improve surgical stress levels,degrees of pain,emotional state,quality of life,and nursing satisfaction of patients with gallstones and reduce the incidence of complications.

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.

Analysis of factors impacting postoperative pain and quality of life in patients with mixed hemorrhoids:A retrospective study

BACKGROUND Hemorrhoids are among the most common and frequently encountered chronic anorectal diseases in anorectal surgery.They are venous clusters formed by con-gestion,expansion,and flexion of the venous plexus in the lower part of the rec-tum.Mixed hemorrhoids bleed easily and recurrently,and this can result in severe anemia.Hence,they may have a negative effect on the health of the patient and surgical treatment is required.Milligan-Morgan hemorrhoidectomy has been widely used since 1937 for the treatment of grade III and IV hemorrhoids.How-ever,most patients experience different degrees of postoperative pain that may cause anxiety.with mixed hemorrhoids post-surgery.METHODS The clinical data of patients with mixed hemorrhoids who underwent Milligan-Morgan hemorrhoidectomy were collected retrospectively.The basic character-istics of the enrolled patients with mixed hemorrhoids were recorded,and based on the Goligher clinical grading system,the hemorrhoids were classified as grades III or IV.The endpoint of this study was the disappearance of pain in all patients.Quantitative data were presented as mean±SD,such as age,pain score,and QoL score.Student’s t-test was used to compare the groups.RESULTS A total of 164 patients were enrolled.The distribution of the visual analog scale pain scores of all patients at 3,7,14 and 28 d after surgery showed that post-surgery pain was significantly reduced with the passage of time.Fourteen days after the operation,the pain had completely disappeared in some patients.Twenty-eight days after the surgery,none of the patients experienced any pain.Comparing the World Health Or-ganization Quality of Life-BREF self-reporting questionnaire scores of patients between 14 and 28 d after surgery,we observed that the quality-of-life scores of the patients post-surgery had significantly improved.There were six items that were compared at 14-and 28-d post-surgery.The mean QoL score 28 d after surgery(4.79±0.46)was higher than that at 14 d post-surgery(3.79±0.57).The mean health condition score 28 d after surgery(4.80±0.41)was also higher than that at 14 d post-surgery(4.01±0.62).The mean physical health score 28 d after surgery(32.10±2.96)was significantly higher than that at 14 d post-surgery(23.41±2.85).The mean psychological health score 28 d after surgery(27.22±1.62)was significantly higher than that at 14 d post-surgery(21.37±1.70).The mean social relations score 28 d after surgery(12.21±1.59)was significantly higher than that at 14 d post-surgery(6.32±1.66).The mean surrounding environment score 28 d after surgery(37.13±2.88)was significantly higher than that at 14 d post-surgery(28.42±2.86).The differences in quality-of-life scores at day 14 and day 28 post-surgery were ob-served to be statistically significant(P<0.001).CONCLUSION Milligan-Morgan hemorrhoidectomy can significantly improve the postoperative QoL of patients.Age,sex,and the number of surgical resections were important factors influencing Milligan-Morgan hemorrhoidectomy.

Genetic Evidence for Causal Association Between Hypertension and Chronic Pain:A Bidirectional Two-Sample Mendelian Randomization Study

Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed.In the present study,Mendelian randomization(MR)was employed to examine the potential causal relationship between hypertension and risk of chronic pain.Methods The study data were derived from the pooled dataset of the genome-wide association study(GWAS),enabling the evaluation of the causal effects of hypertension on various types of chronic pain including chronic headache as well as chest,abdominal,joint,back,limb,and multisite chronic pain.We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting(IVW),MR-Egger,weighted median,and weighted mode,quantified by odds ratio(OR).Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache(OR=1.007,95%CI:1.003-1.011,P=0.002)and limb pain(OR=1.219,95%CI:1.033-1.439,P=0.019).No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR(P>0.05).In addition,there was no potential causal association between secondary hypertension and chronic pain(P>0.05).Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain,and no causal relationship was found between secondary hypertension and chronic pain.These findings offer theoretical underpinnings for future research on managing hypertension and chronic pain.

Application of buried auricular point combined with Wenjing Sanhan prescription in arteriosclerosis obliterans patients with resting pain

BACKGROUND Research on the combined use of ear acupoint embedding beans and warming meridians with cold-dispersing formulas for alleviating resting pain in patients with arteriosclerosis obliterans(ASO)remains limited.AIM To explore the therapeutic efficacy of auricular point embedding beans combined with Wenjing Sanhan prescription in alleviating resting pain in patients with lower-limb ASO.METHODS A total of 100 patients with ASO experiencing resting pain who were treated at our hospital from January 2022 to January 2023 were enrolled.They were randomly allocated into two groups using a double-blind approach.The control group was treated using a warming meridian with a cold-dispersing formula,while the study group received additional treatment with ear acupoint embedding beans.The clinical efficacy,ankle-brachial artery pressure ratio,hemorheological indicators,and traditional Chinese medicine symptom scores were compared between the two groups.RESULTS The clinical efficacy rate in the study group was significantly higher(94.00%)than that in the control group(72.00%,P<0.05).Moreover,the ankle-brachial artery pressure ratio was significantly higher in the study group after treatment(P<0.05).Hemorheological parameters,including whole blood viscosity,plasma viscosity(1.83±0.11)mPa/s,fibrinogen levels(3.30±0.21)g/L,platelet adhesion rate(49.87%±10.51%),and erythrocyte aggregation index(1.79±0)were improved in the study group compared to the control group.In addition,the scores for decreased skin temperature(1.41±0.26),intermittent claudication(1.30±0.20),and resting pain(1.23±0.31)were significantly lower in the study group than those in the control group(all P<0.05).The level of oxidative stress in the study group also exhibited significant improvement(P<0.05),and the levels of inflammatory factors were considerably lower than those in the control group.CONCLUSION The combination of ear point embedding beans and Wenjing Sanhan prescription demonstrates promising clinical efficacy in alleviating resting pain associated with ASO.

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.

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.

Acute abdominal pain from ovarian endometriosis

Endometriosis is a common,estrogen-dependent,inflammatory,gynecologic disease process in which normal endometrial tissue is abnormally present outside the uterine cavity.[1]Endometriosis is a common cause of chronic pain,dyspareunia,dysmenorrhea,and infertility.Most commonly,endometriosis is found within the pelvis,specifically on the ovaries.Because of rupture,bleeding,infection,or torsion,ovarian endometriosis(OMA)may cause acute abdominal pain,which is similar to acute abdominal pain caused by other reasons and is not easy to diagnose.[2,3]Determining the clinical and pathological features of OMA is crucial for accurate assessment,diagnosis,and treatment.

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.

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.

Commentary on“Synchronized activity of sensory neurons initiates cortical synchrony in a model of neuropathic pain”

In pat i e nt s,a s well as in animal mod e l s,hypersensitivity to external stimuli(hyperalgesia and allodynia)or spontaneous pain is often the first,and the most disabling,symptom of neuropathy(Davis et al.,2020).The increased activity of sensitive neurons drives pain development,making ion channel modulation a fundamental target for current pharmacotherapy as well as one of the most investigated by the R&D departments of pharmaceutical companies(Bennett et al.,2019).

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.

Percutaneous cervical cordotomy for managing refractory pain in a patient with a Pancoast tumor:A case report

BACKGROUND According to the World Health Organization analgesic ladder,cancer-related pain generally begins with pharmacotherapy in a stepwise approach.Nevertheless,some patients continue to experience poorly controlled pain despite medications,particularly when considering adverse effects and self-care quality.Percutaneous cervical cordotomy is an alternative interventional procedure for unremitting unilateral intractable cancer-related pain.CASE SUMMARY The patient was diagnosed with lung cancer with destruction of the brachial plexus and ribs.For 2 mo,the patient experienced progressive severe weakness and pain in the right upper extremity.Notably,the pain intensity reached an extreme level,particularly when lying supine,even under heavy sedation.This heightened pain response posed a significant challenge;as a result,the patient was unable to undergo further evaluation through magnetic resonance imaging.Ultimately,he underwent percutaneous cervical cordotomy for symptom relief,resulting in complete resolution of right arm pain.After a 3-mo follow-up,the pain did not recur,and only a flurbiprofen local patch was required for mild scapular tightness.CONCLUSION Cordotomy,under careful patient selection,appears to enhance the quality of life of patients with unilateral cancerrelated pain.

Brain regulates weight bearing bone through PGE2 skeletal interoception: implication of ankle osteoarthritis and pain

Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.