Treatment Of Pain Research Articles

A pilot study of precision treatment for patients with lung cancer pain by Longteng Tongluo recipe using serum genomics.

To investigate the efficacy of Longteng Tongluo recipe (, LTTL) combined with three-step analgesia for the treatment of lung cancer pain, and the changes in serum miRNA expressions before- and after treatment with LTTL and its correlation with lung cancer pain. The possible mechanism underlying LTTL effects on the treatment of lung cancer pain was conducted. The pilot study was conducted at the oncology ward of the Yueyang Hospital and the Longhua Hospital between March 2018 and October 2019. A prospective, single-blind, placebo controlled, randomized clinical trial of LTTL or placebo combined with three-step analgesia treatments were administered to 24 cancer pain patients diagnosed with lung cancer. Analgesic efficacy was investigated as the primary outcome. Equivalent morphine consumption and numerical rating scale (NRS) scores were used as the secondary outcome. In the present study, we utilized deep sequencing techniques to compare the differential miRNA expressions in serum samples obtained from two groups: the lung cancer pain treatment group (LTTL + three-step analgesia) and the control group (placebo + three-step analgesia). Next, we employed the target prediction database to investigate the target genes for differential miRNA expressions and Gene Ontology (GO) analysis along with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to examine the roles and the major biochemical and signaling pathways related to the differentially expressed target genes, respectively. LTTL treatment significantly reduces the NRS score (P = 0.021) as compared to those before treatment, along with significant reductions in the total morphine equivalent consumption (P = 0.007) and the average daily equivalent morphine consumption (P = 0.003) as opposed to the control group. The expressions of 31 miRNAs differed considerably between the two groups of patients (≥ 2 times up-modulated or down-regulated between these groups, P<0.05). For instance, the miRNAs expression levels for patients before treatment (has-miR-2110 and has-miR-7d-3p) were significantly enhanced as compared to the healthy people, after LTTL treatment, the expressions of miR-2110 and miR-7d-3p in patients with lung cancer pain reduced significantly. Studies show that the above two miRNAs were significantly associated with lung cancer pain, which could mediate lung cancer pain. Furthermore, we identified 355 genes as potential targets of the 31 differentially expressed miRNAs. Pathway enrichment analyses using KEGG and GO analysis indicated that these target genes may play a crucial role in the development and modulation of lung cancer pain. LTTL demonstrated a discernible impact on alleviating lung cancer pain and its mechanism of action may be related to the downregulation of has-miR-2110 and has-miR-7d-3p expressions. This pilot study provides support for further exploration of LTTL in patients with lung cancer pain.

Central Neuropathic Pain

ABSTRACT OBJECTIVE This article provides an approach to the assessment, diagnosis, and treatment of central neuropathic pain. LATEST DEVELOPMENTS Recent studies of the pathophysiology of central neuropathic pain, including evidence of changes in the expression of voltage-gated sodium channels and N-methyl-d-aspartate (NMDA) receptors, may provide the basis for new therapies. Other areas of current research include the role of cannabinoid-receptor activity and microglial cell activation in various animal models of central neuropathic pain. New observations regarding changes in primary afferent neuronal activity in central neuropathic pain and the preliminary observation that peripheral nerve blocks may relieve pain due to central neuropathic etiologies provide new insights into both the mechanism and treatment of central neuropathic pain. ESSENTIAL POINTS In the patient populations treated by neurologists, central neuropathic pain develops most frequently following spinal cord injury, multiple sclerosis, or stroke. A multimodal, individualized approach to the management of central neuropathic pain is necessary to optimize pain relief and may require multiple treatment trials to achieve the best outcome.

Chronic Pain Psychology in Neurology Practice

ABSTRACT OBJECTIVE This article reviews the latest literature regarding chronic pain epidemiology and describes pain-specific psychological factors associated with the development and maintenance of chronic pain, mental health conditions that co-occur with chronic pain, and advances in the psychobehavioral treatment of chronic pain, including established treatments (ie, cognitive behavioral therapy [CBT], acceptance and commitment therapy, and mindfulness-based stress reduction) and emerging treatments (ie, pain reprocessing therapy). LATEST DEVELOPMENTS In addition to CBT and acceptance and commitment therapy for pain, numerous other psychological treatment modalities have been integrated into chronic pain management, including mindfulness-based stress reduction, mindfulness meditation, chronic pain self-management, relaxation response, pain neuroscience education, biofeedback, hypnosis, and, more recently, integrative psychological treatment for centralized pain. This article gives an overview of these methods and contextualizes their use within the standard psychological treatment of chronic pain. ESSENTIAL POINTS Guided by the biopsychosocial treatment model, pain psychologists use numerous evidence-based psychological methods to treat patients with chronic pain conditions. Familiarity with the psychological tools available for pain management will aid neurologists and their patients in navigating the psychological aspects of living with chronic pain.

Network-based pharmacology and experimental validation to explore the mechanism of action of the Jiawei Pentongling formula for the treatment of endometriosis-related pain.

To investigate the effects and mechanisms of the Jiawei Pentongling formula (, JWPTL) in treating endometriosis-related pain using network pharmacology study and experimental validation. Active ingredients and relevant targets of JWPTL, as well as genes for endometriosis-related pain, were collected from public databases. Prediction of core targets and pathways of JWPTL against pain associated with endometriosis by protein-protein interaction (PPI) network work, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. The Sprague-Dawley rat endo-metriosis model was constructed using the autologous endosomal transplantation method, and the successfully modeled rats were randomly divided into the model group and the JWPTL group, with 8 rats in each group. Another 8 rats were set up in the sham group. Rats in the JWPTL group used the rectal delivery method with the addition of JWPTL (7.77 g·kg-1·d-1) once a day for 28 d. Rats in the model and sham-operated groups were given equal amounts of saline using the same administration method. The 50% paw withdrawal threshold (PWT) of the rats was measured at different time points. After the intervention, the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) proteins and mRNA in endometriotic tissues was detected by immune-ohistochemistry and reverse transcription-polymerase chain reaction. From GeneCards, Online Mendelian Inheritance in Man and other databases, a total of 964 endometriosis (EMs) -related pain targets were screened, 142 active ingredients of JWPTL, 605 targets, and 221 potential targets were obtained by intersection of Venn diagram; 44 core targets were identified by constructing PPI network. KEGG enrichment analysis showed that JWPTL mainly involves the PI3K-Akt signaling pathway, estrogen signaling pathway, hypoxia inducible factor-1 signaling pathway, tumour necrotizing factor signaling pathway, and other signaling pathways in the treatment of EMs-related pain. Animal experiments showed that JWPTL could up-regulate the mechanical pain threshold and reduce the expression of PI3K and Akt proteins and mRNA in ectopic endometrial tissues of model rats. The present study preliminarily analyzed the pharmacological mechanism of the formula, and molecular docking and animal experiments showed the feasibility of this study, suggesting that the formula may inhibit the release of inflammatory factors and reverse the pain associated with EMs by downregulating the PI3K/Akt signaling pathway.

The Clinical Implications of Transdermal Baclofen in the Management of Mild-Moderate Neuropathic Pain

The pharmacotherapeutic management of chronic pain is a particular challenge for healthcare providers, as patients often require multimodal analgesia and polypharmacy in order to achieve symptomatic relief. Patient adherence, frequent dose titration, patient comorbidities, and individual characteristics can further complicate treatment and limit treatment options at the outpatient level. The therapeutic potential of localized analgesia in the treatment of chronic pain is of particular interest to healthcare providers nationwide, as it provides a necessary alternative to systemic analgesia. Compounding Pharmacies and FDA Outsourcing Facilities aid in this endeavor through endogenous compounding and manufacturing (respectively) of externally-applied pain formulations. This review summarizes the available clinical evidence supporting transdermal baclofen utilization in the symptomatic management of chronic musculoskeletal and/or neuropathic pain. The adjunctive treatment of pain from a localized perspective remains under-investigated, and the role of transdermal analgesics/antispasmodics in chronic pain management remains uncertain.

Predicting the Mechanism of Tiannanxing-shengjiang Drug Pair in Treating Pain Using Network Pharmacology and Molecular Docking Technology.

This study aimed to analyze the potential targets and mechanism of the Tiannanxing-shengjiang drug pair in pain treatment using network pharmacology and molecular docking technology. The active components and target proteins of Tiannanxing-Shengjiang were obtained from the TCMSP database. The pain-related genes were acquired from the DisGeNET database. The common target genes between Tiannanxing-Shengjiang and pain were identified and subjected to the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses on the DAVID website. AutoDockTools and molecular dynamics simulation analysis were used to assess the binding of the components with the target proteins. Ten active components were screened out, such as stigmasterol, β-sitosterol, and dihydrocapsaicin. A total of 63 common targets between the drug and pain were identified. GO analysis showed the targets to be mainly associated with biological processes, such as inflammatory response and forward regulation of the EKR1 and EKR2 cascade. KEGG analysis revealed 53 enriched pathways, including pain-related calcium signaling, cholinergic synaptic signaling, and serotonergic pathway. Five compounds and 7 target proteins showed good binding affinities. These data suggest that Tiannanxing-shengjiang may alleviate pain through specific targets and signaling pathways. The active ingredients in Tiannanxing-shengjiang might alleviate pain by regulating genes, such as CNR1, ESR1, MAPK3, CYP3A4, JUN, and HDAC1 through the signaling pathways, including intracellular calcium ion conduction, cholinergic prominent signaling, and cancer signaling pathway.

Recent advances in acupuncture for pain relief.

Acupuncture therapy has achieved global expansion and shown promise for health promotion and treatment of acute/chronic pain. To present an update on the existing evidence base for research and clinical practice supporting acupuncture analgesia. This Clinical Update elaborates on the 2023 International Association for the Study of Pain Global Year for Integrative Pain Care "Factsheet Acupuncture for Pain Relief" and reviews best evidence and practice. Acupuncture is supported by a large research evidence base and growing utilization. Mechanisms of acupuncture analgesia include local physiological response at the needling site, suppression of nociceptive signaling at spinal and supraspinal levels, and peripheral/central release of endogenous opioids and other biochemical mediators. Acupuncture also produces pain relief by modulating specific brain networks, integral for sensory, affective, and cognitive processing, as demonstrated by neuroimaging research. Importantly, acupuncture does not just manage pain symptoms but may target the sources that drive pain, such as inflammation, partially by modulating autonomic pathways. Contextual factors are important for acupuncture analgesia, which is a complex multifaceted intervention. In clinical practice, historical records and many providers believe that acupuncture efficacy depends on specific acupoints used, the technique of needle placement and stimulation, and the person who delivers the procedure. Clinical research has supported the safety and effectiveness of acupuncture for various pain disorders, including acupuncture as a complementary/integrative therapy with other pain interventions. Although the quality of supportive evidence is heterogeneous, acupuncture's potential cost-effectiveness and low risk profile under standardized techniques suggest consideration as a neuromodulatory and practical nonpharmacological pain therapy.

Pronociceptive role of spinal Cav2.3 (R-type) calcium channels in a mouse model of postoperative pain.

More than 80% of patients may experience acute pain after a surgical procedure, and this is often refractory to pharmacological intervention. The identification of new targets to treat postoperative pain is necessary. There is an association of polymorphisms in the Cav2.3 gene with postoperative pain and opioid consumption. Our study aimed to identify Cav2.3 as a potential target to treat postoperative pain and to reduce opioid-related side effects. A plantar incision model was established in adult male and female C57BL/6 mice. Cav2.3 expression was detected by qPCR and suppressed by siRNA treatment. The antinociceptive efficacy and safety of a Cav2.3 blocker-alone or together with morphine-was also assessed after surgery. Paw incision in female and male mice caused acute nociception and increased Cav2.3 mRNA expression in the spinal cord but not in the incised tissue. Intrathecal treatment with siRNA against Cav2.3, but not with a scrambled siRNA, prevented the development of surgery-induced nociception in both male and female mice, with female mice experiencing long-lasting effects. High doses of i.t. SNX-482, a Cav2.3 channel blocker, or morphine injected alone, reversed postoperative nociception but also induced side effects. A combination of lower doses of morphine and SNX-482 mediated a long-lasting reversal of postsurgical pain in female and male mice. Our results demonstrate that Cav2.3 has a pronociceptive role in the induction of postoperative pain, indicating that it is a potential target for the development of therapeutic approaches for the treatment of postoperative pain.

ID: 334966 Pulsed Radiofrequency Treatment for Chronic Pain: Real-World Outcomes In Europe

ID: 334966 Pulsed Radiofrequency Treatment for Chronic Pain: Real-World Outcomes In Europe

Out-of-Hospital Intranasal Ketamine as an Adjunct to Fentanyl for the Treatment of Acute Traumatic Pain: A Randomized Clinical Trial

ObjectiveTo evaluate if prehospital administration of fentanyl and intranasal ketamine, compared to fentanyl alone, improves early pain control after injury. MethodsWe conducted a prehospital randomized, placebo-controlled, blinded, parallel group clinical trial from October 2017 to December 2021. Participants were male, aged 18-65 years, receiving fentanyl to treat acute traumatic pain prior to hospital arrival, treated by an urban fire-based EMS agency, and transported to the region’s only adult Level I Trauma Center. Participants randomly received 50mg intranasal ketamine or placebo. The primary outcome was the proportion with a minimum two-point reduction in self-described pain on the Verbal Numerical Rating Scale thirty minutes after study drug administration assessed by 95% confidence interval overlap. Secondary outcomes were side effects, pain ratings, and additional pain medications through the first three hours of care. ResultsIn the 192 enrolled, 89 (46%) were White, 36 [27, 53] (median [IQR]) years old, with 103 receiving ketamine and 89 receiving placebo. There was no difference in the proportion experiencing improved pain 30-minutes after treatment (46/103 [44.7%] ketamine vs. 32/89 [36.0%] placebo, difference in proportions 8.7% [95% CI -5.1% to 22.5%]. p=0.22) or at any timepoint through three hours. There was no difference in secondary outcomes or side effects. ConclusionsIn our sample, we did not detect an analgesic benefit of adding 50mg intranasal ketamine to fentanyl in prehospital trauma patients.

Sodium aescinate alleviates neuropathic pain through suppressing OGT-mediated O-GlcNAc modification of TLR3 to inactivate MAPK signaling pathway

Neuropathic pain results from damage to nerves or the brain, and is characterized by symptoms such as allodynia, spontaneous pain, and hyperalgesia. The causes of this type of pain are intricate, which can make it difficult to treat. Sodium aescinate (SA), a natural extract from horse chestnut tree seeds, has been shown to act as a neuroprotector by inhibiting microglia activation. This study aims to explore the therapeutic potential of SA for neuropathic pain and the molecular mechanisms regulated by SA treatment. Through in vivo animal models and experiments, we found that SA treatment significantly reduced mechanical allodynia and heat hyperalgesia in neuropathic pain models. Additionally, SA inhibited O-GlcNAc-transferase (OGT)-induced O-GlcNAcylation (O-GlcNAc) modification in neuropathic pain mice. OGT overexpression could impede the therapeutic effects of SA on neuropathic pain. Further investigation revealed that Toll-like receptor 3 (TLR3), stabilized by OGT-induced O-GlcNAc modification, could activate the Mitogen activated protein kinase (MAPK) signaling pathway. Further in vivo experiments demonstrated that TLR3-mediated p38 mitogen-activated protein kinase (p38MAPK) activation is involved in SA-mediated relief of neuropathic pain. In conclusion, this study uncovers a novel molecular pathway deactivated by SA treatment in neuropathic pain.

Antidepressants for pain management in adults with chronic pain: a network meta-analysis.

Chronic pain is common and costly. Antidepressants are prescribed to reduce pain. However, there has not been a network meta-analysis examining all antidepressants across all chronic pain conditions, so effectiveness and safety for most antidepressants for pain conditions remain unknown. To assess the efficacy and safety of antidepressants for chronic pain (except headache) in adults. Our primary outcomes were as follows: substantial pain relief (50%), pain intensity, mood and adverse events. Our secondary outcomes were as follows: moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change, serious adverse events and withdrawal. This was a systematic review with a network meta-analysis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, AMED and PsycINFO databases for randomised controlled trials of antidepressants for chronic pain conditions up until 4 January 2022. The review was registered in PROSPERO (CRD42020171855), and the protocol was published in the Cochrane Library (https://doi.org/10.1002/14651858.CD014682). We analysed trials from all settings. We included trials in which participants had chronic pain, defined as longer than 3 months, from any condition excluding headache. We included all antidepressants. Our primary outcome was substantial pain relief, defined as a reduction ˃ 50%. We also measured pain intensity, mood and adverse events. Secondary measures included moderate pain relief (above 30% reduction), physical function, sleep, quality of life, Global Impression of Change, serious adverse events, and withdrawal from trial. We identified 176 studies with a total of 28,664 participants. Most studies were placebo-controlled (n = 83) and parallel armed (n = 141). The most common pain conditions examined were fibromyalgia (59 studies), neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of randomised controlled trials was 10 weeks. Most studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. Standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that for duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. The evidence for antidepressants other than duloxetine is poor. For duloxetine, it is not clear whether the effect applies to groups with both pain and low mood, since these groups were excluded from trials. There is also insufficient evidence on long-term outcomes and on adverse effects. There is only reliable evidence for duloxetine in the treatment of chronic pain. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Data for all other antidepressants were of low certainty. However, the findings should not be read as an encouragement to prescribe antidepressants where other non-pharmacological intervention could be equally effective, especially in the absence of good evidence on side effects and safety. There is a need for large, methodologically sound trials testing the effectiveness of antidepressants for chronic pain. These trials should examine long-term outcomes (> 6 months) and include people with low mood. There should also be better reporting of adverse events, tolerance of drugs, and long-term compliance. This study is registered as PROSPERO CRD42020171855. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128782) and is published in full in Health Technology Assessment; Vol. 28, No. 62. See the NIHR Funding and Awards website for further award information.

ID: 336602 Topiramate-Induced Hearing Loss in Treatment of Chronic Low Back Pain: A Case Study

ID: 336602 Topiramate-Induced Hearing Loss in Treatment of Chronic Low Back Pain: A Case Study

ID: 319034 Real-World Outcomes Following 60-day PNS for the Treatment of Chronic Pain in a Medicare-Eligible Cohort

ID: 319034 Real-World Outcomes Following 60-day PNS for the Treatment of Chronic Pain in a Medicare-Eligible Cohort

Outcome measures and their importance for effective equine back pain rehabilitation

Effective rehabilitation for equine back pain is required due to the frequency of dysfunction effecting performance and welfare. Reliable and valid measures should be used establish a baseline in pain and dysfunction levels, and used to monitor change during rehabilitation, as well as support future research assessing the efficacy of treatment interventions. Such measures are collectively known as outcome measures and can include specific objective markers of impairments such as reduced range of motion, or pain on palpation. The aim of this narrative review is to discuss the options and tools available to use as outcome measures in relation to the treatment and rehabilitation of back pain in the horse. In this paper outcome measures critically discussed relate to conformation and standing posture, muscle dimensions, palpation, range of motion, objective gait analysis, functional analysis, owner reported outcome measures and pain scales. Recommendations are made to assist with selection of a suitable outcome measure. In conclusion, complex laboratory-based analysis systems are available to be gold-standard truly objective systems, although realism for clinical practitioners working in the field limits their use. There is a requirement for new outcome measures that are not subject to observer bias nor time or financially consuming, however it is possible to use those available currently with assist in clinical decision making for the benefit of the horse.

Discovery of a novel KV7.2/7.3 channels agonist for the treatment of neuropathic pain

Discovery of a novel KV7.2/7.3 channels agonist for the treatment of neuropathic pain

Pediatric Pain

ABSTRACT OBJECTIVE This article reviews pain disorders encountered in pediatric neurology practice and provides current information regarding the assessment and treatment of pediatric chronic pain. LATEST DEVELOPMENTS Data about pediatric pain management remain sparse, owing to a dearth of controlled trials and longitudinal studies in these patients. However, the field of pain management and understanding of central and peripheral pain processing has expanded to allow more effective treatment of a broad group of children and adolescents with pain associated with neurologic disease. Neuroimaging visualizes sensory and nonsensory systems, and genetic markers of sensitivity and disease may guide specific therapy. The concept of central sensitization in chronic pain disorders has supported the development of multidisciplinary paradigms for the comprehensive care of these patients. ESSENTIAL POINTS Pain involves sensory activation and central nervous system modulation in pediatric patients. Pediatric neurologists should be prepared to define, investigate, and treat pain disorders in this complex patient population. Appropriate interventions during childhood may attenuate or prevent chronic pain later in life. Current interventions include behavioral, physical, and pharmacologic approaches, as well as potential noninvasive tools for neuromodulation. Research is progressing in sensory measurement, neuroimaging, genetics, and neuroinflammation to guide future targeted therapies.

ID: 344560 Spinal cord stimulation as a dual-purpose treatment for Spinal Cord Injury, Pain and Functional Restoration

ID: 344560 Spinal cord stimulation as a dual-purpose treatment for Spinal Cord Injury, Pain and Functional Restoration

Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.

Humans have long been combating chronic pain. In clinical practice, opioids are firstchoice analgesics, but long-term use of these drugs can lead to serious adverse reactions. Finding new, safe and effective pain relievers that are useful treatments for chronic pain is an urgent medical need. Based on accumulating evidence from numerous studies, excess reactive oxygen species (ROS) contribute to the development and maintenance of chronic pain. Some antioxidants are potentially beneficial analgesics in the clinic, but ROS-dependent pathways are completely inhibited only by scavenging ROS directly targeting cellular or subcellular sites. Unfortunately, current antioxidant treatments do not achieve this effect. Furthermore, some antioxidants interfere with physiological redox signaling pathways and fail to reverse oxidative damage. Therefore, the key upstream processes and mechanisms of ROS production that lead to chronic pain in vivo must be identified to discover potential therapeutic targets related to the pathways that control ROS production in vivo. In this review, we summarize the sites and pathways involved in analgesia based on the three main mechanisms by which ROS are generated in vivo, discuss the preclinical evidence for the therapeutic potential of targeting these pathways in chronic pain, note the shortcomings of current research and highlight possible future research directions to provide new targets and evidence for the development of clinical analgesics.

Modified lumbar-sacral Esp block for the treatment of low back pain

Modified lumbar-sacral Esp block for the treatment of low back pain