Effective Pain Treatment Research Articles

Is transcutaneous electrical nerve stimulation an effective treatment for low back pain?

Eisenhower Army Medical Center, Fort Gordon, GA The corresponding author is Jason Lanham; [email protected] The authors have no conflicts of interest to disclose. The opinions and assertions contained herein are those of the authors and are not to be construed as official or as reflecting the views of the U.S. Army Medical Department, the Army at large, or the Department of Defense.

Bibliometric Analysis of Research Trends on Tuina Manipulation for Neck Pain Treatment Over the Past 10 Years.

Tuina is an effective treatment for neck pain (NP). However, there has been no bibliometric analysis of the global application and emerging trends of tuina performed for NP. Therefore, this study aimed to provide an overview of the current state and future trends in the field. Articles about tuina for NP, published from January 1, 2013, to January 1, 2023, were searched in the Web of Science Core Collection database. CiteSpace (6.1.R6) and VOSviewer (1.6.18) software were used to analyze annual trends in literature posts, countries, institutions, authors, cited references, and knowledge graphs of keyword co-occurrence, clustering, and burst using standard bibliometric indicators. The final analysis comprised 505 valid documents. The results demonstrate that the number of articles in the field of tuina therapy for NP has gradually increased over the years, showing the most active countries, institutions, journals, and authors. There were 323 keywords in the field, 322 research authors, and 292 research institutions, with the USA having the most publications (n = 140). The most published institution is Vrije University Amsterdam, and the most published journal is the Cochrane Database of Systematic Reviews. Peter R Blanpied is the most influential and most-cited author. Interventions (dry needling, massage therapy, and muscle energy techniques), common treatment sites for NP (upper trapezius), and complications (cervicogenic headache) are the top three frontiers mentioned in the field of tuina research for NP. The bibliometric study showed the current status and trends in clinical research on treating patients with NP using tuina, which may help researchers identify topics of interest and scope for future research in this field.

ID: 210977 Human Perception of Sensing Evoked Compound Action Potential During Spinal Cord Stimulation

Spinal cord stimulation (SCS) is an effective chronic pain treatment, which relies on programming based on patients’ perception of stimulation. Stimulation efficacy changes as the spinal cord moves. Therefore, sensing evoked compound action potential (ECAP) and adjusting stimulation based on ECAP may provide a way to maintain therapy effectiveness [1,2,3,4]. Here, we quantify the ECAP response-dose curves with patients’ perception to understand how to utilize ECAP during potential stimulation adjustment.

ID: 223284 An Objective Analysis of Functional Changes With Spinal Cord Stimulation (SCS)

Introduction: Spinal cord stimulation is an effective treatment for pain of the trunk and extremities as supported by several decades of experience and multiple studies. The current “gold-standard” to indicate therapeutic benefit and enable insurance coverage is achieving at least a 50% reduction in pain during the trial. Some centers choose 5-7day trials and in others extended trials are required to confirm benefit. In addition, previous patient reports suggest a reduction in efficacy over time and the development of “tolerance”. Accumulating evidence suggests a significant relationship between pain level and functional performance.

Case Report: Lower Extremity Paresthesia and Pain with Diabetic Polyneuropathy Combated with Complex Korean Medical Treatment

Background: Diabetic polyneuropathy is the most common complication in diabetics, occurring in 50% of all cases. About 10-20% of all diabetics are accompanied by neurological pain, showing a tendency to increase with age. Clinical aspects are very diverse, from mild abnormalities on nerve conduction tests to severe abnormalities in all sensory, motor, and autonomic nerves; however, sensory symptoms usually precede motor symptoms. Patients typically express sensory symptoms, such as positive and negative symptoms, which decrease the quality of life and have marked clinical implications, such as increased morbidity and mortality. Although Western medical drugs, such as tricyclic antidepressants, anticonvulsants, and narcotic analgesics, are used for diabetic polyneuropathy, a standard treatment has not been established.Case report: A 65-year-old male with paresthesia and pain due to diabetic polyneuropathy was treated with <i>Uchashinki-hwan</i>, acupuncture, electroacupuncture, moxibustion, and Jungsongouhyul pharmacopuncture for 10 days. We used the Toronto Clinical Neuropathy Scoring System, EuroQol-5 Dimension, and Visual Analog Scale to evaluate symptoms. Subsequently, the Neuropathy Scoring System, EuroQol-5 Dimension, and subjective discomfort improved.Conclusion: The present case report suggests that combined Korean medicine treatment might be an effective treatment for paresthesia and pain with diabetic polyneuropathy. Several follow-up studies should be conducted to clarify the effectiveness of the treatment.

RNA-Seq Reveals Sex Differences in Gene Expression during Peripheral Neuropathic Inflammation and in Pain Relief from a COX-2 Inhibiting Theranostic Nanoemulsion.

Given decades of neuroinflammatory pain research focused only on males, there is an urgent need to better understand neuroinflammatory pain in females. This, paired with the fact that currently there is no long-term effective treatment for neuropathic pain furthers the need to evaluate how neuropathic pain develops in both sexes and how it can be relieved. Here we show that chronic constriction injury of the sciatic nerve caused comparable levels of mechanical allodynia in both sexes. Using a COX-2 inhibiting theranostic nanoemulsion with increased drug loading, both sexes achieved similar reduction in mechanical hypersensitivity. Given that both sexes have improved pain behavior, we specifically explored differential gene expression between sexes in the dorsal root ganglia (DRG) during pain and relief. Total RNA from the DRG revealed a sexually dimorphic expression for injury and relief caused by COX-2 inhibition. Of note, both males and females experience increased expression of activating transcription factor 3 (Atf3), however, only the female DRG shows decreased expression following drug treatment. Alternatively, S100A8 and S100A9 expression appear to play a sex specific role in relief in males. The sex differences in RNA expression reveal that comparable behavior does not necessitate the same gene expression.

Machine Learning in Spinal Cord Stimulation for Chronic Pain.

Spinal cord stimulation (SCS) is an effective treatment for chronic neuropathic pain. The success of SCS is dependent on candidate selection, response to trialing, and programming optimization. Owing to the subjective nature of these variables, machine learning (ML) offers a powerful tool to augment these processes. Here we explore what work has been done using data analytics and applications of ML in SCS. In addition, we discuss aspects of SCS which have narrowly been influenced by ML and propose the need for further exploration. ML has demonstrated a potential to complement SCS to an extent ranging from assistance with candidate selection to replacing invasive and costly aspects of the surgery. The clinical application of ML in SCS shows promise for improving patient outcomes, reducing costs of treatment, limiting invasiveness, and resulting in a better quality of life for the patient.

Increasing the Passive Range of Joint Motion in Stroke Patients Using Botulinum Toxin: The Role of Pain Relief.

By blocking the release of neurotransmitters, botulinum toxin A (BoNT-A) is an effective treatment for muscle over-activity and pain in stroke patients. BoNT-A has also been reported to increase passive range of motion (p-ROM), the decrease of which is mainly due to muscle shortening (i.e., muscle contracture). Although the mechanism of action of BoNT-A on p-ROM is far from understood, pain relief may be hypothesized to play a role. To test this hypothesis, a retrospective investigation of p-ROM and pain was conducted in post-stroke patients treated with BoNT-A for upper limb hypertonia. Among 70 stroke patients enrolled in the study, muscle tone (Modified Ashworth Scale), pathological postures, p-ROM, and pain during p-ROM assessment (Numeric Rating Scale, NRS) were investigated in elbow flexors (48 patients) and in finger flexors (64 patients), just before and 3-6 weeks after BoNT-A treatment. Before BoNT-A treatment, pathological postures of elbow flexion were found in all patients but one. A decreased elbow p-ROM was found in 18 patients (38%). Patients with decreased p-ROM had higher pain-NRS scores (5.08 ± 1.96, with a pain score ≥8 in 11% of cases) than patients with normal p-ROM (0.57 ± 1.36) (p < 0.001). Similarly, pathological postures of finger flexion were found in all patients but two. A decreased finger p-ROM was found in 14 patients (22%). Pain was more intense in the 14 patients with decreased p-ROM (8.43 ± 1.74, with a pain score ≥ 8 in 86% of cases) than in the 50 patients with normal p-ROM (0.98 ± 1.89) (p < 0.001). After BoNT-A treatment, muscle tone, pathological postures, and pain decreased in both elbow and finger flexors. In contrast, p-ROM increased only in finger flexors. The study discusses that pain plays a pivotal role in the increase in p-ROM observed after BoNT-A treatment.

Combined Programmed Intermittent Bolus and Patient-Controlled Bolus Is a More Favorable Setting for Epidural Pain Relief Than Continuous Infusion.

Epidural analgesia is a suitable and effective treatment for labor pain. However, the preferable modality setting for delivery remains debatable. This study adopted a programmed intermittent epidural bolus (PIEB) setting in conjunction with a patient-controlled epidural analgesia (PCEA) setting to improve the quality of labor analgesia and reduce the number of medical staff. We conducted a prospective observational analysis of primigravida parturients scheduled for spontaneous labor, which required epidural analgesia for painless labor. A total of 483 healthy primigravida parturients with singleton pregnancies were included in this cohort; 135 nulliparous patients were assigned to the continuous infusion setting (CEI) group and 348 to the PIEB + PCEA group. Compared to the CEI setting, the PIEB + PCEA setting significantly reduced the manual rescue by the clinician, extended the time required for the first manual rescue dose, and acclaimed good maternal satisfaction. The use of the CEI mode increased for poor performance requiring more than two rescues with an odds ratio of 2.635 by a binary logistic regression analysis. Using the PIEB + PCEA setting as the maintenance infusion had a longer duration for the first requested manual rescue, fewer manual rescue boluses, excellent satisfaction, and no significant increase in adverse events compared to the CEI setting.

Effectiveness of music therapy within community hospitals: an EMMPIRE retrospective study.

Given the challenges health systems face in providing effective nonpharmacologic treatment for pain and psychological distress, clinical effectiveness studies of evidence-based strategies such as music therapy (MT) are needed. This study examined changes in patient-reported outcomes (PROs) after MT and explored variables associated with pain reduction of ≥2 units on a 0 to 10 numeric rating scale (NRS). A retrospective review was conducted on initial MT interventions provided to adults receiving community hospital care between January 2017 and July 2020. Sessions were included if participants reported pre-session pain, anxiety, and/or stress scores of ≥4 on the NRS. Data analysis included a bootstrap analysis of single-session changes in PROs and a logistic regression exploring variables associated with pain reduction (ie, ≥2 units vs <2 units). Patients (n = 1056; mean age: 63.83 years; 76.1% female; 57.1% White; 41.1% Black/African American) reported clinically significant mean reductions in pain (2.04 units), anxiety (2.80 units), and stress (3.48 units). After adjusting for demographic, clinical, and operational characteristics in the model (c-statistic = 0.668), patients receiving an MT session in which pain management was a goal were 4.32 times more likely (95% confidence interval 2.26, 8.66) to report pain reduction of ≥2 units than patients receiving an MT session in which pain management was not a session goal. This retrospective study supports the clinical effectiveness of MT for symptom management in community hospitals. However, additional research is needed to determine which characteristics of MT interventions and patients influence pain change.

Molecular and Epigenetic Aspects of Opioid Receptors in Drug Addiction and Pain Management in Sport.

Opioids are substances derived from opium (natural opioids). In its raw state, opium is a gummy latex extracted from Papaver somniferum. The use of opioids and their negative health consequences among people who use drugs have been studied. Today, opioids are still the most commonly used and effective analgesic treatments for severe pain, but their use and abuse causes detrimental side effects for health, including addiction, thus impacting the user's quality of life and causing overdose. The mesocorticolimbic dopaminergic circuitry represents the brain circuit mediating both natural rewards and the rewarding aspects of nearly all drugs of abuse, including opioids. Hence, understanding how opioids affect the function of dopaminergic circuitry may be useful for better knowledge of the process and to develop effective therapeutic strategies in addiction. The aim of this review was to summarize the main features of opioids and opioid receptors and focus on the molecular and upcoming epigenetic mechanisms leading to opioid addiction. Since synthetic opioids can be effective for pain management, their ability to induce addiction in athletes, with the risk of incurring doping, is also discussed.

Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain.

Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1β in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased β-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic β-endorphin. Refractory animals showed increased TNF-α and decreased IFNγ in the nerve, along with decreased TNF-α and IL-17A in the DRG, maintaining low levels of systemic β-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain.

A standardized anesthetic/analgetic regimen compared to standard anesthetic/analgetic regimen for patients with high-risk factors undergoing open lumbar spine surgery: a prospective comparative single-center study.

The objective of the study is to improve the results of patients undergoing lumbar spine surgery who are at high risk for anesthesia and/or surgical complications. Two independent groups were compared: the study group (SG, n = 40) (standardized neuroanesthetic protocol with multimodal analgesia) and the control group (CG, n = 40) (intravenous anesthesia based on propofol and fentanyl). The data were collected using prospective observation of early and long-term results of lumbar fusion. After 24months, the level of functional state and quality of life were studied. Patients in the SG did not have statistically significant changes in intraoperative hemodynamics; the best indicators of cognitive functions were noted. The effectiveness of the SG compared with the CG was confirmed by a statistically significantly lower amount of perioperative opioid drugs required (p = 0.01) and a minimal level of incisional pain (p < 0.05). An intergroup comparison of the adverse effects of anesthesia revealed a significantly lower number in the SG (n = 4) compared to the CG (n = 16) (p = 0.004). The number of postoperative surgical complications was comparable (p = 0.72). Intergroup comparison showed improved ODI, SF-36, and the Macnab scale at 24months after surgery in the SG compared to the CG (p < 0.05). Long-term clinical results correlated with the level of incisional pain in the first three postoperative days. Our standardized neuroanesthetic protocol ensured effective treatment of postoperative incisional pain, significantly decreased the perioperative use of opioids, reduced adverse anesthesia events, and improved long-term clinical results in patients with high risk factors for anesthetic complications who undergoing open lumbar spine surgery.

Comparison of Tertiary Drug Information Resources With the CDC Guideline for Oxycodone Dosing: Are Patients at Risk?

Background: Inappropriate prescribing of opioids is thought to play a central role in the ongoing opioid health crisis. Tertiary information resources are commonly used by clinicians for obtaining opioid dosing information. To assist health care providers in pain management, the Centers for Disease Control and Prevention (CDC) developed a guideline for prescribing opioids. Objective: To identify discrepancies for dosing information on oxycodone between commonly used tertiary drug information resources and the CDC Guideline. Methods: Searches of the tertiary drug information resources were conducted in the following order: Facts and Comparisons, Lexicomp, Medscape, and Micromedex. The term "oxycodone" was entered in the search box in the tertiary resources' applications. Drug information items retrieved were organized in tabular format. In the Google Chrome version 106.0.5249.119 search box, the term "CDC guideline for opioid dosing" was entered to retrieve current information on the CDC Guideline. Results: Searches produced drug information on oxycodone for available formulations, dosing regimens, recommended dosing, and maximum daily dose (MDD). Searches revealed discrepancies in dosing recommendations for oxycodone among tertiary drug resources and between tertiary drug resources and the CDC Guideline. Conclusions: When considering maximum daily dosing information for oxycodone from the selected tertiary drug information resources, the potential exists for patients to be at risk of addiction, overdose, and perhaps death. Improving the way opioids are prescribed through the CDC Clinical Practice Guideline can ensure patients have access to safer, more effective chronic pain treatment while reducing the number of people who misuse or overdose from inappropriate dosing information.

Multiple modulatory roles of serotonin in chronic pain and injury-related anxiety.

Chronic pain is long-lasting pain that often persists during chronic diseases or after recovery from disease or injury. It often causes serious side effects, such as insomnia, anxiety, or depression which negatively impacts the patient's overall quality of life. Serotonin (5-HT) in the central nervous system (CNS) has been recognized as an important neurotransmitter and neuromodulator which regulates various physiological functions, such as pain sensation, cognition, and emotions-especially anxiety and depression. Its widespread and diverse receptors underlie the functional complexity of 5-HT in the CNS. Recent studies found that both chronic pain and anxiety are associated with synaptic plasticity in the anterior cingulate cortex (ACC), the insular cortex (IC), and the spinal cord. 5-HT exerts multiple modulations of synaptic transmission and plasticity in the ACC and the spinal cord, including activation, inhibition, and biphasic actions. In this review, we will discuss the multiple actions of the 5-HT system in both chronic pain and injury-related anxiety, and the synaptic mechanisms behind them. It is likely that the specific 5-HT receptors would be new promising therapeutic targets for the effective treatment of chronic pain and injury-related anxiety in the future.

Histochemical analysis of the biphasic properties of formalin pain-induced behavior

The formalin test has been established as a method for evaluating mouse models of pain. Although there have been numerous reports of formalin-pain-induced behavior, few reports of a detailed histochemical analysis of the central nervous system focus on behavioral biphasic properties.To investigate the alternation of spinal neuronal activity with formalin-induced pain, we performed immunofluorescent staining with c-Fos antibodies as neuronal activity markers using acute pain model mice induced by 2% formalin stimulation. As a result, phase-specific expression patterns were observed. In the spinal dorsal horn region, there were many neural activities in the deep region (layers V−VII) in the behavioral first phase and those in the surface region (layers I−III) in the behavioral second phase. Furthermore, we conducted comparative studies using low concentrations (0.25%) of formalin and capsaicin, which did not show distinct behavioral biphasic properties. Neural activity was observed only in the spinal dorsal horn surface region for both stimuli.Our study suggested that the histochemical biphasic nature of formalin-induced pain was attributable to the activity of the deep region of the spinal cord. In the future, treatment strategies focusing on the deep region neuron will lead to the development of effective treatments for allodynia and intractable chronic pain.

Clinical assessment and risk stratification for prehospital use of methoxyflurane versus standard analgesia in adult patients with trauma pain.

Oligoanalgesia, the undertreatment of trauma-related pain using standard analgesics in prehospital and emergency departments, has been extensively documented as one of the major challenges affecting the effective treatment of trauma-related pain. When administered in low doses, methoxyflurane has been highlighted by numerous medical works of literature to provide an effective, nonopioid, nonnarcotic treatment alternative to standard analgesics for prehospital and emergency department use. Low-dose methoxyflurane has been associated with fast-pain relief in adult patients manifesting moderate-to-severe pain symptoms. This systematic review and meta-analysis aimed to assess the clinical implication of low-dose methoxyflurane use in prehospital and emergency departments in adult patients with moderate-to-severe trauma-related pain. Moreover, the review aimed at assessing the risk stratification associated with using low-dose methoxyflurane in prehospital and emergency departments. The systematic review and meta-analysis performed a comprehensive search for pertinent literature assessing the implications and risks of using low-dose methoxyflurane in adult patients exhibiting moderate-to-severe trauma-related pain in prehospital settings. A comparison between the use of low-dose methoxyflurane and standard-of-care analgesics, placebo, in prehospital settings was reported in four clinically conducted randomized controlled trials (RCTs). These RCTs included the STOP! trial, InMEDIATE, MEDIATA, and the PenASAP trials. A meta-analysis comparing the time taken to achieve first pain relief on initial treatment of patients with moderate-to-severe trauma-related pain favored the use of low-dose methoxyflurane to the standard-of-care analgesics (mean difference = -6.63, 95% confidence interval = -7.37, -5.09) on time taken to establish effective pain relief. Low-dose methoxyflurane has been associated with superior and faster pain relief in prehospital and emergency departments in adult patients exhibiting moderate-to-severe trauma-related pain compared to other standard analgesics.

Radiofrequency Ablation for Chronic Lumbar Zygapophyseal Joint Pain Using a V-Shaped Active Tip Needle: An Observational Retrospective Study.

Lumbar zygapophyseal joint dysfunction represents one of the major sources of chronic low back pain. Radiofrequency ablation (RFA) using a V-shaped active tip needle may offer a larger lesion of the medial branch nerves, improving clinical outcome. The aim of our study is to evaluate the efficacy and the feasibility of RFA using V-shaped active tip needles. This is a single-center observational retrospective study. Clinical records were screened and analyzed if they met the following inclusion criteria: adult patients (>18 years), diagnosis of chronic lumbar zygapophyseal joint pain, failure of conservative treatments, ability to provide informed consent for data analysis and publication. Exclusion criteria: lumbar pain not related to zygapophyseal joints, previous spinal/lumbar surgery, incomplete data, absence or withdrawal of informed consent. The primary outcome of the study was a change in pain intensity at follow-up. The secondary outcomes were the evaluation of quality-of-life improvement, the occurrence of adverse events and the impact on post-procedural analgesic consumption. For these purposes, pre- and post-treatment numeric rating scale (NRS), neuropathic pain 4 questions (DN4), EuroQoL - EQ-5D-3L, EQ-VAS, EQ-index and North American Spine Society (NASS) index were retrieved and analysed. Sixty-four patients were included. 7.8% of patients at 1-month (CI95% 0.026, 0.173), 37.5% at 3-month (CI95% 0.257, 0.505), 40.6% at 6-month (CI95% 0.285, 0.536) and 35.9% at 9-month (CI95% 0.243, 0.489) follow-up reported a reduction of more than 80% in NRS Statistical analysis indicated a significant change in NRS, DN4, EQ-index and EQ-5D-VAS (p-value <0.001) at the different time-points. RFA using a V-shaped active tip needle might be a feasible and effective treatment for chronic lumbar zygapophyseal joint pain.

Pain treatment options for osteoarthritis.

Osteoarthritis is one of the most common diseases of the joints and spine and is characterized by degenerative changes starting in the cartilage. Joint changes cause pain, stiffness, swelling, and a loss of normal joint function. Several international recommendations address the choice of treatment methods for osteoarthritis. However, because there is still no effective causal treatment leading to a remission of the disease, this is a complex issue. Even the possibilities of effective but safe treatment of pain, which is the most common problem accompanying osteoarthritis, are very limited. All current international recommendations for the treatment of osteoarthritis agree on the crucial role of non-pharmacological treatment and the choice of a comprehensive approach to the treatment of osteoarthritis. Pharmacological treatment includes non-opioid analgesics, opioids, symptomatic slow-acting osteoarthritis drugs, or intra-articular corticosteroids. A new trend is to maximize the potential of existing analgesics by combining them. Using drugs from different classes with complementary mechanisms of action provides a better opportunity for effective analgesia at reduced doses of individual agents. The use of fixed combinations is also advantageous.

Response to Arendt-Nielsen et al. (Methodology considerations for the paper by Hosted et al. 2023).

Response to Arendt-Nielsen et al. (Methodology considerations for the paper by Hosted et al. 2023).