Relief Of Chronic Pain Research Articles

AB205. SOH22ABS234. Patient positions and ultrasound guided chronic pain interventions

Background: Image guidance is commonly used in chronic pain intervention procedures. Guidance modalities include fluoroscopy, CT, magnetic resonance imaging (MRI) and ultrasound. Ultrasound guidance is growing in popularity due to absence of radiation, absence of dye injections, decreased cost and spectrum of utility. Another potential benefit is more comfortable patient positioning, reduction in stress for patients regarding positioning and intervention and reduced procedure time. This benefit of ultrasound-guided injections for single and multi-source have not been studied. The aim of this study was to examine these potential benefits of ultrasound guided chronic pain relief procedures.

Sustained endosomal release of a neurokinin-1 receptor antagonist from nanostars provides long-lasting relief of chronic pain

Soft polymer nanoparticles designed to disassemble and release an antagonist of the neurokinin 1 receptor (NK1R) in endosomes provide efficacious yet transient relief from chronic pain. These micellar nanoparticles are unstable and rapidly release cargo, which may limit the duration of analgesia. We examined the efficacy of stable star polymer nanostars containing the NK1R antagonist aprepitant-amine for the treatment of chronic pain in mice. Nanostars continually released cargo for 24 h, trafficked through the endosomal system, and disrupted NK1R endosomal signaling. After intrathecal injection, nanostars accumulated in endosomes of spinal neurons. Nanostar-aprepitant reversed mechanical, thermal and cold allodynia and normalized nociceptive behavior more efficaciously than free aprepitant in preclinical models of neuropathic and inflammatory pain. Analgesia was maintained for >10 h. The sustained endosomal delivery of antagonists from slow-release nanostars provides effective and long-lasting reversal of chronic pain.

MANAGEMENT TACTICS OF PATIENTS WITH HYPERPLASTIC SYNDROME AND ANEMIA

Abstract. The study of this clinical case made it possible to demonstrate the effectiveness of the management tactics of a patient with hyperplastic syndrome and anemia using hormone therapy with Buserelin- Long (an agonist of Hh-RG) for six months, followed by an operative stage (uterine artery embolization). The patient had relief of chronic pelvic pain by the third month of treatment with Buserelin -Long. In the future, the patient did not have a resumption of pain syndrome. During the control examination of the patient six months after the start of treatment, positive dynamics in the treatment of the hyperplastic process was revealed, expressed in a decrease in the size of intramural myomatous nodes, the absence of recurrence of the endometrial hyperplastic process, relief of pain and abnormal uterine bleeding. At the initial treatment of the patient, clinical and laboratory data were revealed confirming her chronic posthemorrhagic iron deficiency anemia. The indicators of clinical and biochemical blood tests reached the limits of reference values during the control examination after 6 months of Buserelin –Long therapy, which indicates the effectiveness of this management tactic in patients with hyperplastic syndrome and anemia. No adverse reactions were detected during treatment. The patient noted the good tolerability of the drug as well as the rapid and effective relief of the manifestations of the disease. Thus, based on the study of this clinical case, we can conclude about the effectiveness of the proposed management tactics for a patient with hyperplastic syndrome and anemia and recommend the use of this type of therapy in patients with similar pathology.

Botulinum toxin type a combined with transcranial direct current stimulation reverses the chronic pain induced by osteoarthritis in rats

Osteoarthritis (OA) is the most common cause to lead to chronic pain. Sensitization of pain pathways including central sensitization and peripheral sensitization has been regarded as a major cause of OA pain refractory to treatment. Addressing peripheral sensitization or central sensitization alone may not adequately treat OA pain. In our previous studies, botulinum toxin type A (BoNT/A) has been shown to reduce peripheral sensitization for analgesic effects. In addition, transcranial direct current stimulation (tDCS) has also been suggested to reduce central sensitization for analgesia. The present study was designed to investigate whether BoNT/A in combination with tDCS has better analgesic effects than isolated treatment to alleviate OA-induced chronic pain in rats. The Von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. The expression level of N-methyl-D-aspartate receptor-2B (NMDAR2B) was evaluated in midbrain periaqueductal gray (PAG) by Western blot the Immunohistochemistry staining after different treatments. The results showed that the combined treatment of BoNT/A and tDCS better improved the pain-related behaviors and significantly increased the expression level of NMDAR2B protein in PAG than each isolated treatment. These results suggested that the combined treatments for relief of chronic pain were more obvious than each isolated treatment. The combination of BoNT/A and tDCS may relieve pain by increasing N-methyl-D-aspartate (NMDA) receptors in the PAG, and then the descending inhibitory systems were activated to modulate peripheral and central sensitization.

SIRT1: A promising therapeutic target for chronic pain.

Chronic pain remains an unresolved problem. Current treatments have limited efficacy. Thus, novel therapeutic targets are urgently required for the development of more effective analgesics. An increasing number of studies have proved that sirtuin 1 (SIRT1) agonists can relieve chronic pain. In this review, we summarize recent progress in understanding the roles and mechanisms of SIRT1 in mediating chronic pain associated with peripheral nerve injury, chemotherapy‐induced peripheral neuropathy, spinal cord injury, bone cancer, and complete Freund's adjuvant injection. Emerging studies have indicated that SIRT1 activation may exert positive effects on chronic pain relief by regulating inflammation, oxidative stress, and mitochondrial dysfunction. Therefore, SIRT1 agonists may serve as potential therapeutic drugs for chronic pain.

Ilioinguinal and Iliohypogastric Nerve Block for Acute and Chronic Pain Relief After Caesarean Section: A Randomized Controlled Trial.

BackgroundThere is an increasing cesarean section (CS) rate in Egypt. Multiple methods are used to manage pain after CS. ObjectivesThis study aimed to assess the effect of ultrasound-guided bilateral ilioinguinal and iliohypogastric nerve block on pain reduction after CS.MethodsWe classified 64 cases of elective CS into two equal groups. The block group underwent the nerve block, and the control group did not. Postoperative pain, morphine consumption, time to analgesic request, and complications were compared between the two groups. ResultsNo significant difference was detected between the two groups regarding patient characteristics or operation duration. However, pain scores during rest and movement were significantly lower in the block group than in controls, especially within the first 12 hours following the operation. Morphine consumption was significantly lower in the block group (4.53 ± 1.456) in group B vs. (8.87 ± 2.013) in group C with P-value < 0.001. Time to the first rescue analgesia was significantly longer in the intervention group than in the other group (12.25 vs. 3.81 hours). Pruritis and nausea incidence was significantly higher in controls than in the block group. The incidence of chronic postoperative pain was significantly lower in the block group.ConclusionsThe ilioinguinal and iliohypogastric nerve block is efficient and safe for managing postoperative pain following CS. It is associated with significant improvement of acute and chronic pain after such operations.

New perspective of acupuncture analgesia: reward of chronic pain relief and related brain reward circuits

Relief of the chronic pain, as the negative reinforcement of pain, is recognized as a reward and it activates related brain's reward circultries. Brian's reward circuits not only relate to rewards, but also participate in pain process. Currently, the reward effect of acupuncture on chronic pain relief and the mechanism of brain's reward circuits involved in acupuncture analgeisa have not been revealed adequately yet. This paper reviewed the conceptual features of analgesia reward and the new progression of brain's reward circuits and function, expounded the valuable clinical and scientific significance of the researches for the reward effect of acupuncture analgesia and related brain's reward circuits, proposed the ideas and suggestions on many questions in the study of reward effect of acupuncture analgesia and related brain's reward circuits, and then, determined the multi-dimensional characteristis and positive regulation of acupuncture analgesia. Focusing on the reward effect of acupuncture and related brain's reward circuits for chronic pain relief, the research on the regulatory effect of acupuncture analgesia will be conductive to deepen the understanding of acupuncture analgies in clinical practice and innovate a research concept of acupuncture analgeis. Eventually, a new approach can be provided to further elaborate neurobiolgical mechanism of acupuncture analgesia.

Using Essentrics to Improve the Health of Older Adults

Essentrics, like Tai Chi, is a low to moderate impact exercise activity that is suitable for older adults. The exercise may offer the benefits of increased strength, flexibility, functional mobility, enhanced balance and relief for chronic pain.

831 Pain Networks Connectivity Changes Following the Relief of Prolonged Cancer Pain

INTRODUCTION: The “salience network” is normally engaged in humans’ response to acute internal or environmental stimuli, including pain. It comprises connections between the anterior insula (AI) and dorsal anterior cingulate cortex (dACC), among others. Chronic pain conditions have been associated with abnormally increased functional connectivity (FC) within the salience network in comparison to healthy individuals. METHODS: We prospectively followed patients that underwent cervical cordotomy (n=15) and cingulotomy (n=11) for relief of intractable oncological pain during the years 2016-2019. All patients did resting-state functional Magnetic Resonance Imaging (rsfMRI) before and after the procedures. Clinical data was collected, including pre- and post-operative numeric rating scale (NRS) pain scores. RESULTS: All patients (aged 62±11) reported a significant improvement in their pain from NRS 9±1 to 1±1 in cordotomy (p=0.001) and 2±3 in cingulotomy (p=0.005). By comparing pre- and post-operative rsfMRI scans, we demonstrated a significant decrease in the FC between components of the salience network following both cordotomy (p=0.007) and cingulotomy (p=0.009). In the cordotomy group we found a significant decrease in the connectivity between the thalamus and dACC (p=0.019) and within the sensory-motor cortex (p=0.003). CONCLUSIONS: Surgical interventions along the pain pathways can lead to a sudden relief of chronic pain in parallel to a significant decrease in the functional connectivity within pain related networks.

Success of lateral cervical spinal cord stimulation for the treatment of chronic neuropathic refractory pain.

Background: Spinal cord stimulation (SCS) is traditionally performed by implanting surgical leads along the midline of the spinal cord, over the dorsal columns. Here, we present a patient who successfully underwent lateral cervical SCS to treat chronic refractory neuropathic pain.Methods: A 46-year-old female, with a schwannoma involving the right axillary nerve, presented with a chronic refractory right upper extremity pain syndrome. The tumor was located between the fibers of the teres minor and the posterior deltoid, and measured 2.2 cm in diameter. After 8 months of analgesics, opioids, physiotherapy, and acupuncture, the patient underwent surgery; however, the tumor was unresectable (i.e., due to significant adjacent vascular/neural structures). Three months later, she had a midline C6-C7 laminectomy for placement of a right-sided epidural SCS lead (i.e., containing 16 electrode contacts).Results: Within 4 days following this SCS procedure, the patient’s pain completely resolved; at 10 postoperative months, she still remains pain free.Conclusion: Lateral SCS at the C6-C7 level provided a safe and effective option for the relief of chronic neuropathic pain attributed to an unresectable schwannoma of the right axillary nerve in a 46-year-old female.

The Role of Spinal Cord Stimulation in Reducing Opioid Use in the Setting of Chronic Neuropathic Pain: A Systematic Review.

The aim was to examine research on the impact of spinal cord stimulation (SCS) on the reduction of preimplantation opioid dose and what preimplantation opioid dose is associated with a reduction or discontinuation of opioid use postimplantation. Systematic review of literature from PubMed, Web of Science, and Ovid Medline search of "opioid" and "pain" and "spinal cord stimulator." Inclusion criteria included original research providing data on SCS preimplantation opioid dosing and 12 months postimplantation opioid dosing or that correlated specific preimplantation opioid dose or opioid dose cutoff with significantly increased likelihood of opioid use discontinuation at 12 months postimplantation. Systematic review of the literature yielded 17 studies providing data on pre-SCS and post-SCS implantation dose and 4 providing data on the preimplantation opioid dose that significantly increased likelihood of opioid use discontinuation at 12 months postimplantation. Data from included studies indicated that SCS is an effective tool in reducing opioid dose from preimplantation levels at 12 months postimplantation. Data preliminarily supports the assertion that initiation of SCS at a preimplantation opioid dose of ≤20 to ≤42.5 morphine milligram equivalents increases the likelihood of postimplantation elimination of opioid use. SCS is an effective treatment for many types of chronic pain and can reduce or eliminate chronic opioid use. Preimplantation opioid dose may impact discontinuation of opioid use postimplantation and the effectiveness of SCS in the relief of chronic pain. More research is needed to support and strengthen clinical recommendations for initiation of SCS use at lower daily opioid dose.

New pharmacological perspectives and therapeutic options for opioids: Differences matter.

Opioids remain the major drug class for the treatment of acute, chronic and cancer pain, but have major harmful effects such as dependence and opioid-induced ventilatory impairment. Although no new typical opioids have come onto the market in the past almost 50 years, a plethora of new innovative formulations has been developed to meet the clinical need. This review is intended to shed light on new understanding of the molecular pharmacology of opioids, which has arisen largely due to the genomic revolution, and what new drugs may become available in the coming years. Atypical opioids have and are being developed which not only target the mu opioid receptor but other targets in the pain pathway. Biased mu agonists have been developed but remain 'unbiased' clinically. The contribution of drugs targeting non-mu opioid receptors either alone or as heterodimers shows potential promise but remains understudied. That gene splice variants of the mu opioid receptor produce multiple receptor isoforms in different brain regions, and may change with pain chronicity and phenotype, presents new challenges but also opportunities for precision pain medicine. Finally, that opioids also have pro-inflammatory effects not aligned with mu opioid receptor binding affinity implicates a fresh understanding of their role in chronic pain, whether cancer or non-cancer. Hopefully, a new understanding of opioid analgesic drug action may lead to new drug development and better precision medicine in acute and chronic pain relief with less patient harm.

Dimethyl itaconate inhibits neuroinflammation to alleviate chronic pain in mice

The metabolite itaconate has both anti-inflammatory and immunomodulatory effects. However, its influence on chronic pain is unclear. Here, we demonstrated that intraperitoneal injection of the itaconate derivative dimethyl itaconate (DI) alleviated chronic pain symptoms, such as allodynia and hyperalgesia, in spinal nerve ligation (SNL) and inflammatory pain models. Moreover, intraperitoneal DI reduced the secretion of inflammatory cytokines (i.e., interleukin-1β, tumour necrosis factor-alpha) in dorsal root ganglion (DRG), spinal cord and hind paw tissues, suppressed the activation of macrophages in the DRG and glial cells in the spinal dorsal horn and decreased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the DRG and spinal cord. DI boosted nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) levels in the DRG and spinal cord of SNL mice. Intraperitoneal administration of the Nrf2 inhibitor ML385 abolished the analgesic effect of DI and decreased the expression of Nrf2 in the DRG and spinal cord. Similarly, administration of DI potently reversed the lipopolysaccharide (LPS)-induced inflammatory effect in microglia. Reduction of endogenous itaconate levels by pretreatment with immune-responsive gene 1 (IRG1) siRNA blocked Nrf2 expression, which impaired the analgesic and anti-inflammatory effects of DI in vitro. Therefore, our findings revealed for the first time that intraperitoneal DI elicited anti-inflammatory effect and sustained chronic pain relief, which may be regarded as a promising therapeutic agent for chronic pain treatment.

Makatoxin-3, a thermostable Nav1.7 agonist from Buthus martensii Karsch (BmK) scorpion elicits non-narcotic analgesia in inflammatory pain models

Ethnopharmacological relevanceChronic pain management represents a serious healthcare problem worldwide. The use of opioid analgesics for pain has always been hampered by their side effects; in particular, the addictive liability associated with chronic use. Finding a morphine replacement has been a long-standing goal in the field of analgesia. In traditional Chinese medicine, processed Buthus martensii Karsch (BmK) scorpion has been used as a painkiller to treat chronic inflammatory arthritis and spondylitis, so called “Scorpio-analgesia”. However, the molecular basis and the underline mechanism for the Scorpio-analgesia are still unclear. Aim of the studyThe study aims to investigate the molecular basis of “Scorpio analgesia” and identify novel analgesics from BmK scorpion. Materials and methodsIn this study, the analgesic abilities were determined using formalin-, acetic acid- and complete Freund's adjuvant-induced pain models. The effect of BmK venom and processed BmK venom on Nav1.7 were detected by whole-cell voltage-clamp recordings on HEK293-hNav1.7 stable cell line. Action potentials in Dorsal root ganglion (DRG) neurons induced by Makatoxin-3-R58A were recorded in current-clamp mode. The content of Makatoxin-3 was detected using competitive enzyme-linked immunosorbent assay based on the Makatoxin-3 antibody. High performance liquid chromatography, western blot and circular dichroism spectroscopy were used to analysis the stability of Makatoxin-3. ResultsHere we demonstrate that Makatoxin-3, an α-like toxin in BmK scorpion venom targeting Nav1.7 is the critical component in Scorpio-analgesia. The analgesic effect of Makatoxin-3 could not be reversed by naloxone and is more potent than Nav1.7-selective inhibitors and non-steroidal anti-inflammatory drugs in inflammatory models. Moreover, a R58A mutant of Makatoxin-3 is capable of eliciting analgesia effect without inducing pain response. ConclusionsThis study advances ion channel biology and proposes Nav1.7 agonists, rather than the presumed Nav1.7-only blockers, for non-narcotic relief of chronic pain.

The changing cannabis culture among older Americans: high hopes for chronic pain relief

Older adults in the U.S. are increasingly using cannabis. Theoretical perspectives of scholars who have explained cannabis use include subcultural theory, normalization thesis, and the age-period-cohort paradigm. Our study examined what influences older adults’ cannabis use, and perceived outcomes of cannabis use. From April 2018 to January 2019, we conducted 12 focus groups with 82 adults aged 60 and older in Illinois, where medical cannabis was legally available beginning in 2014. We used an inductive thematic analysis to code and theme the focus group transcripts and compared the results to concepts and arguments of the three theoretical perspectives. We found four themes: cultural experiences influence older adults’ choice to use cannabis; medical culture and systems impact cannabis use; participants have to navigate a costly and time-consuming state system to use medical cannabis, and; participants experience positive outcomes when using cannabis. Although elements of the three theories can be identified in our findings, subcultural influences of baby boomer counterculture were only relevant for a subset of participants, while normalization of medical cannabis use was not supported by a state system separated from traditional medicine. Medical culture, physical age effects, and prior opioid use were very important in explaining older adults’ cannabis use.

Suprascapular Nerve Block (SSNB) improves the outcome in exercise based management of Primary Adhesive Capsulitis (PAC): A prospective randomized comparative study.

Increased pain and associated stiffness hinders the advantages of exercise and process of recovery in primary adhesive capsulitis. We hypothesized that suprascapular nerve block may positively affect the outcome due to its role in pain relief of acute or chronic shoulder pain. We compared the effect of suprascapular nerve block and exercise with only exercise on the recovery of primary adhesive capsulitis. A total of 96 patients of both sexes presenting with primary adhesive capsulitis were divided by computer randomization in two equal groups (n = 48). Group A received exercise only and Group B received suprascapular nerve block followed by exercise. Oral paracetamol was given for analgesia as desired. Patients were followed up at 4, 8, 16, and 24 weeks. Pain was assessed by visual analog scale; functional outcome by Shoulder Pain and Disability Index and range of movement by goniometer. The pain scores and Shoulder Pain and Disability Index scores were significantly lower at all observation points of 4, 8,16, and 24 weeks in Group B than Group A (P < 0.05). The range of movement in all the ranges of forward flexion, extension, internal and external rotation, and abduction at all observation points was significantly higher in Group-B (P < 0.05) compared to Group A. The consumption of analgesics was significantly more in Group A than Group B at 4 and 8 weeks (P = 0.020 and P = 0.044) but comparable at 12 and 24 weeks (P = 0.145 and P = 0.237 respectively). Combining SSNB with exercise is more effective in treatment of primary adhesive capsulitis than exercise alone and reduces the use of analgesics. SSNB it is effective and safe to use in primary adhesive capsulitis.

Successful Pain Relief of Chronic Myofascial Pain Using Trigger Point Injection and Fascia Hydrorelease with Local Anesthetics Capable of Exerting a Vasoconstrictive Action : Two Case Reports

Successful Pain Relief of Chronic Myofascial Pain Using Trigger Point Injection and Fascia Hydrorelease with Local Anesthetics Capable of Exerting a Vasoconstrictive Action : Two Case Reports

Role of erector spinae plane block in end-of-life care for a patient with advanced abdominal malignancy

Celiac plexus block (CPB) is the most commonly used intervention in patients suffering from pain related to upper abdominal malignancies. Placing a CPB requires a patient to be placed in a prone position on the operating room table which becomes difficult in many patients with advanced disease and therefore makes it more challenging for the interventional pain physician, simultaneously risky for the patient. In such cases, a more superficial minimally invasive intervention is desirable. The erector spinae plane block (ESPB) is one such intervention that has been used in a large variety of settings and can be used in the abovementioned cases. So far, no reports have emphasized the role of this field block for chronic cancer pain relief in a patient with advanced and progressive malignancy nearing the end of life. We present such a case with end-stage carcinoma gallbladder, in which ESPB was used effectively for providing pain relief during her final days.

The Use of Medical Marijuana for the Relief of Chronic Pain

Medical cannabis is safer and more effective than opioids, reducing harm to users and improving and increasing their quality of life.

A Quality-of-Life Evaluation Study Assessing Health-Related Quality of Life in Patients Receiving Medicinal Cannabis (the QUEST Initiative): Protocol for a Longitudinal Observational Study.

BackgroundEvidence supports several countries introducing legislation to allow cannabis-based medicine as an adjunctive treatment for the symptomatic relief of chronic pain, chemotherapy-induced nausea, spasticity in multiple sclerosis (MS), epileptic seizures, depression, and anxiety. However, clinical trial participants do not represent the entire spectrum of disease and health status seen in patients currently accessing medicinal cannabis in practice.ObjectiveThis study aims to collect real-world data to evaluate health-related quality of life in patients prescribed medicinal cannabis oil and describe any differences over time, from before starting therapy to after 3 and 12 months of therapy.MethodsAdult patients newly prescribed medicinal cannabis oil by authorized prescribers and under the Special Access Schemes across Australia will be screened for eligibility and invited to participate. A sample size of 2142 is required, with a 3-month follow-up. All participants will complete the EuroQol 5-Dimension; European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30; Depression, Anxiety, and Stress Scale-21; Patients’ Global Impression of Change; Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form (SF) version 1.0: Sleep Disturbance 8b; and PROMIS SF Fatigue 13a questionnaires. Patients with chronic pain conditions will also complete the PROMIS SF version 1.0: Pain Intensity 3a and PROMIS SF version 1.0: Pain Interference 8a. Patients with movement disorders will also complete Quality of Life in Neurological Disorders (Neuro-QoL) SF version 1.0: Upper Extremity Function (Fine Motor and Activities of Daily Living) and if chorea is indicated, the Neuro-QoL SF version 2.0: Huntington’s Disease health-related Quality of LIFE-Chorea 6a. All questionnaires will be administered at baseline, 2 weeks (titration), monthly up to 3 months, and then every 2 months up to 1 year.ResultsRecruitment commenced in November 2020. By June 2021, 1095 patients were screened for the study by 69 physicians in centers across 6 Australian states: Australian Capital Territory, New South Wales, Queensland, South Australia, Victoria, and Western Australia. Of the patients screened, 833 (39% of the target sample size) provided consent and completed baseline questionnaires. Results are expected to be published in 2022. Results of this study will show whether patient-reported outcomes improve in patients accessing prescribed medicinal cannabis from baseline to 3 months and whether any changes are maintained over a 12-month period. This study will also identify differences in improvements in patient-reported outcomes among patients with different chronic conditions (eg, chronic pain, MS, epilepsy, Parkinson disease, or cancer).ConclusionsThis protocol contains detailed methods that will be used across multiple sites in Australia. The findings from this study have the potential to be integral to treatment assessment and recommendations for patients with chronic pain and other health indicators for accessing medicinal cannabis.Trial RegistrationAustralian New Zealand Clinical Trials Registry: ANZCTRN12621000063819; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380807&isReview=trueInternational Registered Report Identifier (IRRID)DERR1-10.2196/32327