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.

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.

Dental Treatment Using Quantum Mechanics for Knee Joint Pain

In clinical practice, dentists sometimes encounter phenomena that cannot be explained by modern western medical concepts;for example, the patient’s medical symptoms improve by bringing medicines or dentures close to the body. Although it seems difficult to completely elucidate the mechanism through modern western medicine, it can be explained using quantum mechanics. The quantum, the smallest unit of matter composition, exhibits wave-particle duality. The fact that symptoms can be improved simply by bringing dentures or medicines closer to the body indicates that the waves emitted by dentures or medicines interfere with the pathological waves emitted by the pathological site. Thus, the pathological waves are deformed and lead to a change in symptoms. In this way, quantum theory can explain phenomena that are difficult to elucidate in conventional medicine, which are encountered in clinical practice. So far, the author has presented a case of difficulty in raising the upper limb where the symptoms improved without the need for dentures in the mouth by adjusting the dentures outside the mouth. This time, the author would like to introduce a case which the patient’s knee pain improved by adjusting the dentures outside the mouth.

Recent Situation of Acupuncture and Moxibustion in the Treatment of Stomach Pain with Deficiency and Cold of Spleen and Stomach

Stomachache is one of the most common diseases of digestive system, among which stomach pain of deficiency cold of spleen and stomach is the most common. Acupuncture and moxibustion therapy as an external treatment of traditional Chinese medicine for relieving stomach pain due to deficiency of spleen and stomach, has the advantages of convenient operation, small adverse reactions and remarkable curative effect, which is easy for patients to accept. In this paper, acupuncture and moxibustion therapy such as moxibustion and warm acupuncture therapy for stomach pain of spleen and stomach deficiency cold type is summarized to provide evidence-based basis for clinical treatment of stomach pain of spleen and stomach deficiency cold type.

Research trends in exercise therapy for the treatment of pain in postmenopausal osteoporosis over the past decade:A bibliometric analysis

BACKGROUND Postmenopausal osteoporosis(PMOP)is the most common form of primary osteoporosis among women,and the associated pain often drives patients to seek clinical intervention.Numerous studies have highlighted the unique clinical benefits of exercise therapy(ET)in alleviating PMOP-related pain.However,bibliometric analyses examining collaboration,development trends,and research frontiers in the field of ET for PMOP pain remain scarce.AIM To explore the research trends in ET for pain treatment in PMOP patients over the past decade.METHODS All scholarly works were meticulously sourced from the Science Citation Index-Expanded within the prominent Web of Science Core Collection.Utilizing the capabilities of CiteSpace 6.2.R5,we conducted a thorough analysis of publications,authors,frequently cited scholars,contributing nations,institutions,journals of significant citation,comprehensive references,and pivotal keywords.Additionally,our examination explored keyword cooccurrences,detailed timelines,and periods of heightened citation activity.This comprehensive search,from 2014 through 2023,was completed within a single day,on October 11,2023.RESULTS In total,2914 articles were ultimately included in the analysis.There was a rapid increase in annual publication output in 2015,followed by stable growth in subsequent years.Boninger,Michael L,is the most prolific author,whereas Ware JE has the most citations.The United States’global influence is significant,surpassing all other nations.The University of California System and Harvard University are the most influential academic institutions.J Bone Joint Surg Am is the most influential journal in this field.“Spinal cord injury”is the keyword that has garnered the most attention from researchers.The developmental pattern in this field is characterized by interdisciplinary fusion,with different disciplines converging to drive progress.CONCLUSION The academic development of the field of ET for pain in PMOP has matured and stabilized.Clinical management and rehabilitation strategies,along with the mechanisms underlying the relationship between ET and bone resorption analgesia,continue to be the current and future focal points of research in this field.

Evaluation of the Effectiveness and Efficiency of Extracorporeal Shock Wave Combined with Rehabilitation Training in the Treatment of Muscle Articulation Chronic Pain

Objective: To analyze the effect of combined extracorporeal shock wave and rehabilitation training treatment in patients with muscle articulation chronic pain (MACP). Methods: Ninety-seven MACP patients admitted to our hospital from September 2021 to September 2023 were randomly selected and were divided into Group A (control group, 46 cases, rehabilitation training treatment) and Group B (observation group, 51 cases, extracorporeal shock wave with rehabilitation training treatment), and outcomes of the two groups were compared. Results: The treatment efficiency, post-treatment clinical indexes (upper and lower limb function scores, activities of daily living (ADL) scores, visual analog scale (VAS) scores), and short-form 36 (SF-36) scores of Group B were better than those of Group A (P < 0.05). Conclusion: Combined extracorporeal shock wave and rehabilitation training treatment for MACP patients improved their limb function, daily activities, quality of life, and reduced pain.

Clinical efficacy of magnetic vibration magnetoelectric therapy in the treatment of chronic prostatitischronic pelvic pain syndrome

BACKGROUND The prominent symptoms of chronic pelvic pain syndrome(CPPS)are urogenital pain,lower urinary tract symptoms,psychological problems,and sexual dysfunction.Traditional pharmacological treatments have poor efficacy and more untoward reaction and complications.Magnetic vibration magnetoelectric therapy is a non-invasive form of physiotherapy.Nevertheless,its effectiveness in improving urinary discomfort and relieving pain in patients requires further exploration.AIM To investigate the clinical efficacy of the magnetic vibration magnetoelectric therapy instrument in the treatment of chronic prostatitis(CP)/CPPS.METHODS Seventy patients with CP/CPPS were collected from the outpatient clinic and ward of the Department of Male Medicine,Jiangsu Province Hospital of Traditional Chinese Medicine,and were treated with magnetic vibration magnetoelectric therapy once a day for a period of 14 d.National Institutes of healthchronic prostatitis symptom index(NIH-CPSI),international index of erectile function 5(IIEF-5),premature ejaculation diagnostic tool(PEDT),generalized anxiety disorder(GAD),patient health questionnaire,the pain catastrophizing scale(PCS)and traditional Chinese medicine syndrome(TCMS)scores were performed before and after treatment.RESULTS The total effective rate of treatment was 58.5%,and the total NIH-CPSI score,pain symptoms,voiding symptoms,quality of life,IIEF-5,PEDT,GAD,PCS and TCMS scores all decreased significantly(P<0.05).CONCLUSION Magnetic vibration magnetotherapy is effective in improving urinary discomfort,relieving pain,improving quality of life,improving sexual dysfunction and relieving negative emotions such as anxiety in patients with CP/CPPS.

Research Progress of Traditional Chinese Medicine External Treatment for Cancer Pain

Cancer pain,as a common complication in patients with malignant tumors,is regarded as the fifth vital sign.The involvement of traditional Chinese medicine(TCM)in the treatment of malignant tumors has become a distinctive feature of oncology treatment in China.It is also an important component of cancer pain management.TCM analgesic treatments include various methods,such as internal medicine and external therapies.External analgesic therapies,in particular,are significant methods in TCM pain management and offer both local treatment and systemic regulation.These methods are simple,easy to perform,and non-invasive.They can enhance pain relief effects while reducing the difficulty of oral medication intake and avoiding adverse gastrointestinal reactions,providing new perspectives and approaches for cancer pain treatment with broad development prospects.This article provides a review of the external TCM therapies for cancer pain to share with peers in the field.

Clinical Observation of Chinese Medicinal Prescriptions for Swelling and Pain in The Postoperative Treatment of Mixed Hemorrhoids

Objective:To observe the clinical effect of traditional Chinese medicine(TCM)on reducing swelling and pain in patients with mixed hemorrhoids.Methods:Sixty patients with mixed hemorrhoids who were admitted to the Hospital of Traditional Chinese Medicine of Qiqihar from January 2023 to January 2024 were selected and divided into two groups.The treatment group(n=30)was treated with mixed hemorrhoid ligation combined with traditional Chinese swelling and pain medicine,and the control group(n=30)was only treated with mixed hemorrhoid ligation.The pain level,edema score,and prognosis of the two groups after the intervention were analyzed.The clinical efficacy was used as the evaluation criterion to compare the clinical effects of different treatment options.Results:After the treatment,the pain score,edema score,and prognostic wound score of the treatment group were all lower than those of the control group(P 0.05).The total clinical effectiveness of the treatment group(100%)was higher than that of the control group(76.67%),(χ^(2)=4.2857,P<0.05).Conclusion:The application of traditional Chinese swelling and pain medicine in treating patients with mixed hemorrhoids effectively reduced the patient’s pain,reduced the degree of wound edema,promoted wound healing,and improved the patient’s prognosis.The curative effect was significant and had a positive impact.

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.

Clinical Efficacy of Pentoxifylline Combined with Thioctic Acid in the Treatment of Painful Diabetic Peripheral Neuropathy

Objective:To observe the efficacy of pentoxifylline+thioctic acid in the treatment of patients with painful diabetic peripheral neuropathy(PDPN).Methods:70 patients with PDPN admitted from October 2019 to October 2022 were selected and randomly grouped,with pentoxifylline+thioctic acid treatment in Group A and thioctic acid treatment in Group B,and the treatment efficacy was compared.Results:The treatment efficacy in Group A was higher than that of Group B,P<0.05;the points of each symptom of PDPN in Group A were lower than that of Group B,P<0.05;the C-reactive protein and electromyography indexes of PDPN patients in Group A were better than that of Group B,P<0.05.Conclusion:PDPN patients treated with pentoxifylline+thioctic acid can optimize nerve function,inhibit inflammation progression,and reduce PDPN symptoms,which is an efficient and feasible treatment option.

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.

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.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

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.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

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。

Pathophysiology, diagnosis, and treatment of discogenic low back pain

Discogenic low back pain is a serious medical and social problem, and accounts for 26%-42% of the patients with chronic low back pain. Recent studies found that the pathologic features of discs obtained from the patients with discogenic low back pain were the formation of the zones of vascularized granulation tissue, with extensive innervation in fissures extending from the outer part of the annulus into the nucleus pulposus. Studies suggested that the degeneration of the painful disc might originate from the injury and subsequent repair of annulus fibrosus. Growth factors such as basic fibroblast growth factor, transforming growth factor β1, and connective tissue growth factor, macrophages and mast cells might play a key role in the repair of the injured annulus fibrosus and subsequent disc degeneration. Although there exist controversies about the role of discography as a diagnostic test, provocation discography still is the only available means by which to identify a painful disc. A recent study has classified discogenic low back pain into two types that were annular disruption-induced low back pain and internal endplate disruption-induced low back pain, which have been fully supported by clinical and theoretical bases. Current treatment options for discogenic back pain range from medicinal anti-inflammation strategy to invasive procedures including spine fusion and recently spinal arthroplasty. However, these treatments are limited to relieving symptoms, with no attempt to restore the disc's structure. Recently, there has been a growing interest in developing strategies that aim to repair or regenerate the degenerated disc biologically.

Diabetic neuropathic pain:Physiopathology and treatment

Diabetic neuropathy is a common complication of both type 1 and type 2 diabetes,which affects over 90% of the diabetic patients.Although pain is one of the main symptoms of diabetic neuropathy,its pathophysiological mechanisms are not yet fully known.It is widely accepted that the toxic effects of hyperglycemia play an important role in the development of this complication,but several other hypotheses have been postulated.The management of diabetic neuropathic pain consists basically in excluding other causes of painful peripheral neuropathy,improving glycemic control as a prophylactic therapy and using medications to alleviate pain.First line drugs for pain relief include anticonvulsants,such as pregabalin and gabapentin and antidepressants,especial y those that act to inhibit the reuptake of serotonin and noradrenaline.In addition,there is experimental and clinical evidence that opioids can be helpful in pain control,mainly if associated with first line drugs.Other agents,including for topical application,such as capsaicin cream and lidocaine patches,have also been proposed to be useful as adjuvants in the control of diabetic neuropathic pain,but the clinical evidence is insufficient to support their use.In conclusion,a better understanding of the mechanisms underlying diabetic neuropathic pain will contribute to the search of new therapies,but also to the improvement of the guidelines to optimize pain control with the drugs currently available.