Cellular and molecular mechanisms involved in the analgesic effects of botulinum neurotoxin: A literature review.

Botulinum neurotoxins (BoNTs), derived from Clostridium botulinum, have been employed to treat a range of central and peripheral neurological disease. Some studies indicate that BoNT may be beneficial for pain conditions as well. It has been hypothesized that BoNTs may exert their analgesic effects by preventing the release of pain-related neurotransmitters and neuroinflammatory agents from sensory nerve endings, suppressing glial activation, and inhibiting the transmission of pain-related receptors to the neuronal cell membrane. In addition, there is evidence to suggest that the central analgesic effects of BoNTs are mediated through their retrograde axonal transport. The purpose of this review is to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions. Most of the studies reviewed in this article were conducted using BoNT/A. The PubMed database was searched from 1995 to December 2022 to identify relevant literature.

Spatiotemporal analysis of speckle dynamics to track invisible needle in ultrasound sequences using convolutional neural networks: a phantom study.

PURPOSE: Accurate needle placement into the target point is critical for ultrasound interventions like biopsies and epidural injections. However, aligning the needle to the thin plane of the transducer is a challenging issue as it leads to the decay of visibility by the naked eye. Therefore, we have developed a CNN-based framework to track the needle using the spatiotemporal features of the speckle dynamics. METHODS: There are three key techniques to optimize the network for our application. First, we used Gunnar-Farneback (GF) as a traditional motion field estimation technique to augment the model input with the spatiotemporal features extracted from the stack of consecutive frames. We also designed an efficient network based on the state-of-the-art Yolo framework (nYolo). Lastly, the Assisted Excitation (AE) module was added at the neck of the network to handle the imbalance problem. RESULTS: Fourteen freehand ultrasound sequences were collected by inserting an injection needle steeply into the Ultrasound Compatible Lumbar Epidural Simulator and Femoral Vascular Access Ezono test phantoms. We divided the dataset into two sub-categories. In the second category, in which the situation is more challenging and the needle is totally invisible, the angle and tip localization error were 2.43 ± 1.14° and 2.3 ± 1.76 mm using Yolov3+GF+AE and 2.08 ± 1.18° and 2.12 ± 1.43 mm using nYolo+GF+AE. CONCLUSION: The proposed method has the potential to track the needle in a more reliable operation compared to other state-of-the-art methods and can accurately localize it in 2D B-mode US images in real time, allowing it to be used in current ultrasound intervention procedures.

Bier block as a successful management of a patient with intractable complex regional pain syndrome (CRPS) type 1: A case report.

Bier block was successful in the pain management of complex regional pain syndrome (CRPS) type 1.

Preliminary study of analgesic effect of bumetanide on neuropathic pain in patients with spinal cord injury.

BACKGROUND/OBJECTIVE: The current study evaluated the analgesic effects of bumetanide as an adjunctive treatment in managing neuropathic pain following spinal cord injury. The peripheral expression level of Na-K-Cl-cotransporter-1 (NKCC1) and K-Cl-cotransporter-2 (KCC2) genes in polymorphonuclear lymphocytes (PMLs) assessed as a possible biomarker indicating central underlying mechanisms. METHODS: This open-label, single-arm, pilot trial of bumetanide (2 mg/day) is an add-on treatment conducted in 14 SCI patients for 19 weeks. The whole duration consisted of three phases: pre-treatment (1 month), titration (3 weeks), and active treatment (4 months). Ultimately, nine patients completed the study. The primary outcome variables were the endpoint pain score measured by the numeric rating scale (NRS), and the short-form McGill Pain Questionnaire. Secondary endpoints included the Short-Form Health Survey that measures the quality of life. Blood samples were collected and used for determining the expression of NKCC1 and KCC2 genes in transcription and translation levels. RESULTS: Bumetanide treatment significantly reduced average pain intensity according to the NRS and the short form of the McGill Pain Questionnaire scores. The baseline expression of KCC2 protein was low between groups and increased significantly following treatment (P < 0.05). Through the current study, pain improvement accompanied by the more significant mean change from the baseline for the overall quality of life. CONCLUSION: These data might be a piece of preliminary evidence for the analgesic effect of bumetanide on neuropathic pain and could support the potential role of the upregulation of KCC2 protein and involvement of GABAergic disinhibition in producing neuropathic pain.

The Influence of Chronic Pain on Number Sense and Numeric Rating Scale: A prospective Cohort Study.

BACKGROUND: Several studies have demonstrated an association between chronic pain and impairment of cognitive capabilities. Since the number sense is one of the cognitive ability involved in the evaluation of pain intensity using some pain measurement tools, impairment of number sense may impact pain assessment. Therefore, the validity of number-based pain assessment tools should be re-evaluated. OBJECTIVES: This study aimed to determine whether number sense is altered in chronic and acute pain patients compared to healthy subjects. METHODS: Overall, 150 participants were recruited and divided into the three groups of controls, chronic and acute pain patients. Pain intensity was evaluated using numeric and verbal rating scales as pain assessment tools. Number sense was assessed using number naming, number marking, and line bisection tasks. Deviation from correct answers was measured for each task. RESULTS: Patients with chronic pain (migraine headache) had higher pain intensity scores than acute pain subjects. Chronic pain patients showed significant deviation from the expected responses compared to controls in the line bisection task. CONCLUSIONS: Chronic pain patients may have impaired number sense and may differently use number-based pain assessment tools in comparison with healthy individuals.

Predicting Factors of Pain Duration in Patients with Chronic Pain: A Large Population-based Study.

BACKGROUND: Chronic pain is the third main problem of global health and the most common cause of long-term disabilities. The duration that patients suffer from chronic pain is directly proportional to the extent of the suffering and to the amount of health care resources allocated to this problem. There is no research that has studied the risk factors associated with the long pain duration in chronic pain patients. METHODS: We investigated the potential risk factors associated with long pain duration in a population with diverse pain conditions in a cross-sectional study. We used a questionnaire that included a number of potential risk factors including sex, age, marital status, household condition, number of children, employment, education, body mass index (BMI), pain intensity, and the level of anxiety/depression. The data were analyzed by univariable and multivariable linear regression models. RESULTS: We recruited 780 patients. The analyses showed that age and abnormal BMI had a positive correlation with pain duration. CONCLUSIONS: The risk factors that might be associated with longer pain duration include older age and abnormal BMI.

Spinal pain relief procedures with the assistance of the MRI-updated statistical shape model.

BACKGROUND: Updating the statistical shape model (SSM) used in image guidance systems for the treatment of back pain using pre-op computed tomography (CT) and intra-op ultrasound (US) is challenging due to the scarce availability of pre-op images and the low resolution of the two imaging modalities. METHODS: A new approach is proposed here to update SSMs based on the sparse representation of the preoperative MRI images of patients as well as CT images, followed by displaying the injection needle and 3D tracking view of the patients' spine. RESULTS: The statistical analysis shows that updating the SSM using the patients' available MRI images (in more than 95% of the cases) instead of CT images (in less than 5%) will help maintain the required accuracy of needle injection based on the evaluation of injection in different parts of the phantom. CONCLUSION: The results show that using the proposed model helps reduce the dosage and processing time significantly while maintaining the precision required for the pain procedures.

The Efficacy of Sphenopalatine Ganglion Block and Radiofrequency Denervation in the Treatment of Cluster Headache: A Case Series.

BACKGROUND: Cluster headache is a variant of primary neurovascular headaches. some patients with cluster headache are not responsive to medical treatment and may benefit from interventional modalities, including sphenopalatine ganglion block and denervation. OBJECTIVES: Our purpose was to evaluate the efficacy of sphenopalatine ganglion block/denervation in the treatment of cluster headache. METHODS: In this study, we performed the sphenopalatine ganglion block for patients with cluster headaches, intractable to medical therapy, who were referred to our pain clinic between 2014 and 2018. We registered the following information for all patients: demographic data, pain relief, and pain intensity. First, we conducted a prognostic C-arm-guided sphenopalatine ganglion block. If there was at least 50% pain relief within the first 5 h, then we denervated the ganglion by radiofrequency ablation. The main outcome of the study (dependent variable) was pain relief. We followed the patients for 6 months. RESULTS: Among 23 enrolled patients, 19 consented to interventional treatment. Fifteen out of 19 patients (79%) had an acceptable response to the prognostic block. Ultimately, 11 patients underwent ganglion denervation, and 4 patients did not consent for ganglion ablation. Pain relief at intervals of 48 h, and 1, 3, and 6 months after ganglion denervation was 77, 59, 50, and 31 percent, respectively. CONCLUSIONS: Sphenopalatine ganglion conventional radiofrequency denervation can effectively decrease the pain intensity of the patients with cluster headache for at least several months.

Superior Hypogastric Plexus Block in the Lateral Position: A Case Report.

INTRODUCTION: Patients with severe visceral abdominal or pelvic pain are sometimes candidates for celiac or superior hypogastric block. These blocks are performed in the prone position that is usually very painful for these patients. We introduce another position for these blocks that can be better tolerated. CASE PRESENTATION: We performed the superior hypogastric plexus block in the lateral position in a patient who was suffering from severe abdominal and pelvic pain. The procedure was done under the guide of C-Arm fluoroscopy. After the procedure, the pain score reduced to 2 out of 10 on the 11-point Numeric Rating Scale and the patient was discharged without any complication. CONCLUSIONS: Superior hypogastric plexus block in the lateral position was safe and effective for a patient with severe abdominal and pelvic pain.

Assessment of Factors Predicting Inadequate Pain Management in Chronic Pain Patients.

BACKGROUND: Inadequate pain management is highly prevalent and is associated with significant costs and socioeconomic problems, which can lead to disparities in patient care. Specific groups are at higher risk of this problem. A few studies have evaluated the predictive risk factors of inadequate pain management. OBJECTIVES: This study evaluated the prevalence and predictive risk factors of inadequate pain management at the primary and secondary care centers with large sample size. METHODS: Patients who had been managed in primary and secondary care clinics were asked to report their personal characteristics, pain intensity, pain duration, and analgesics they were receiving in their first visit at our pain clinic. Zelman pain management index was calculated for each patient by analgesic potency minus mean pain intensity. The negative index showed incongruence between pain intensity and analgesic potency score (pain stronger than medication), indicating inadequate pain management. RESULTS: A negative pain management index was reported in 77% of the 511 recruited patients. Patients with more severe pain were more likely to experience inadequate pain management. A logistic model demonstrated women, people aged 45 - 65 years, illiterates, and obese patients were at higher risks of inadequate pain management. The pain management index was affected by sex and education (via higher pain intensities) and by age and BMI (via lower analgesic potency). CONCLUSIONS: Age, sex, education, and BMI are predictive risk factors of inadequate pain management as a prevalent problem in chronic pain patients.

The effect of stellate ganglion block on the function of arteriovenous fistulas for hemodialysis: A randomized trial.

BACKGROUND AND PURPOSE: The best access for hemodialysis is an autologous arteriovenous fistula (AVF). The most helpful way for vasodilation in the upper limb is stellate ganglion block. We aim to evaluate the effect of stellate ganglion block on outcome of vascular access for dialysis. MATERIALS AND METHODS: Some 105 hemodialysis patients were randomly allocated to three groups: In group 1, stellate ganglion block was performed before fistula surgery. Group 2 had stellate ganglion block after surgery and group 3 was control group without any block. Primary outcome for all groups was functional dialysis, which is defined as successful hemodialysis for 1 month. RESULTS: The three groups were similar in age, gender, and underlying diseases. Stellate ganglion block before operation had a meaningful increase in successful hemodialysis rate, when compared with the other groups (p = 0.02). CONCLUSION: Stellate ganglion block before arteriovenous fistula surgery in the upper limbs improves hemodialysis success rate.

Characteristics of neuropathic pain in individuals with chronic spinal cord injury.

OBJECTIVE: To present the characteristics of neuropathic pain in individuals with chronic spinal cord injury (SCI). METHODS: We recruited all individuals with chronic SCI referred to the Brain and Spine Injury Research center with a diagnosis of neuropathic pain from April 2013 to September 2015 into this historical cohort study. RESULTS: Forty individuals with chronic SCI-induced neuropathic pain entered this study with a mean age of 43.67+/-13.12 years and a majority of who were male (n=30, 75%). Motor vehicle collision (n=25, 62.5%) and fall (n=7, 17.5%) were the most common causes of SCI in our participants. There were 13 (32.5%) cervical, twenty (50%) thoracic, and 7 (17.5%) lumbosacral SCI. The mean `maximal pain intensity`, `overall pain intensity during the past week`, and `the pain intensity at the initial consultation in pain clinic` measured by numerical rating scale (NRS) in this cohort were 8.71+/-1.73, 6.32+/-1.60, and 6.11+/-2.48, respectively. Burning pain was the most frequently used description of pain reported by our participants. Pain intensity significantly decreased after six months of treatment for all three above categories. CONCLUSION: This study provides characteristics of neuropathic pain in a group of individuals with chronic SCI. Further large prospective studies are needed to determine the association between lesion level, completeness of injury, and region of pain.

Validation of the Persian Version of the Brief Pain Inventory (BPI-P) in Chronic Pain Patients.

CONTEXT: Chronic pain needs to be evaluated with a standard instrument. The Brief Pain Inventory (BPI) is a pain assessment tool that has been validated in many languages. OBJECTIVES: The aim of the present study was to develop the Persian version of the Brief Pain Inventory (BPI-P) and also to evaluate the psychometric properties of the BPI-P in the Iranian population. METHODS: The BPI-P was translated from the original version of BPI using standard procedure. The Persian version of the BPI and 12-item Short-Form Health Survey (SF-12) were completed by 201 patients with chronic pain who were referred to a tertiary pain care clinic from 2013 to 2015. The performance status of the patients was evaluated by physicians using Eastern Cooperative Oncology Group performance test. RESULTS: Factor analysis of the BPI-P identified two scales: pain intensity and pain interference with life. These two factors explained 68.4% of the variance. Coefficient alpha values for BPI-P items ranging from 0.87 to 0.91 showed good internal consistency of the factors. The high intraclass correlation coefficients for the items of the questionnaire confirmed the test-retest reliability for the BPI-P. Patients with higher scores in Eastern Cooperative Oncology Group performance test reported higher levels of pain intensity and pain interference with life. Pain intensity in BPI-P correlated with physical functioning, bodily pain, mental health, and vitality of the SF-12 questionnaire, whereas pain interference was associated with general health, bodily pain, mental health, vitality, and social functioning. CONCLUSION: The present study demonstrated that the Persian version of the BPI could be a valid and reliable instrument for pain assessment in Persian-speaking patients.

Paracetamol 325 mg/tramadol 37.5 mg effect on pain during needle electromyography: a double-blind crossover clinical trial.

Needle insertion during electromyography (EMG) may cause varying levels of pain that could lead to inaccurate assessment and premature termination of the procedure. The aim of this study is to compare paracetamol 325 mg/tramadol 37.5 mg with placebo in relieving pain before EMG. This is a randomized, crossover, placebo-controlled, double-blind clinical trial; forty-four healthy individuals, including 27 males with a mean age of 35.3 years (range 18-59 years), entered this study. The needles were inserted unilaterally 2 h after administration of two analgesic tablets of paracetamol 325 mg/tramadol 37.5 mg or two placebo tablets. The pain was scored through a 100-mm visual analog scale (VAS) immediately and 2 h after the procedure. The side effects were also recorded. Within a week, the procedure was repeated on the other upper limb, changing the treatment and placebo. The immediate and 2-h VAS scores were notably lower after administration of treatment compared to placebo (immediate pain: 17.5 ± 12.8 vs. 32.1 ± 16.0, P < 0.001; and 2-h pain: 1.6 ± 5.6 vs. 5.8 ± 7.9, P = 0. 002). There was a higher prevalence of side effects when treatment was used (48 vs. 9 %, P < 0.001). Although most symptoms were mild, transient and resolved without medical interventions, on one occasion a volunteer experienced brief loss of consciousness and one subject had severe vertigo that required hospitalization and fluid therapy. Paracetamol 325 mg/tramadol 37.5 mg administration prior to EMG could effectively alleviate pain. Further application of this medication in patients with neuromuscular disorders would warrant additional clinical trials, particularly considering the adverse events.

A comparison of metoclopramide and lidocaine for preventing pain on injection of diazepam.

UNLABELLED: We compared the ability of metoclopramide with IV lidocaine pretreatment to abolish pain from a diazepam injection. In a randomized, prospective, double-blinded, placebo-controlled clinical trial, 159 patients (ASA physical status I and II), aged 20-70 yr old, were allocated to one of three groups. Placebo and study drugs were injected IV immediately before 0.1 mg/kg of diazepam into a dorsal hand vein. Patients in Groups 1, 2, and 3 received 2 mL of placebo, 2 mL of lidocaine 1%, and 2 mL of metoclopramide (10 mg), respectively. The patient's response was graded using a 4-point scale. Any score other than 0 represented pain on injection. We observed that the incidence of pain on diazepam injection was 83% in the placebo group, which was decreased to 70% and 39% in patients pretreated with metoclopramide and lidocaine, respectively. Although there was no significant difference in the incidence of pain in Groups 1 and 3 (P > 0.05), Group 3 showed significantly less patients with severe pain scores than Group 1 as diazepam was injected (P < 0.000). Group 2 showed a significantly less frequent incidence of pain than the saline (P < 0.000) and the metoclopramide (P < 0.002) groups as diazepam was injected. The intensity of pain in Group 2 was significantly less than Group 3 (P = 0.012). The intensity of diazepam injection pain was intense with placebo as compared with other groups (P < 0.000). Metoclopramide, rather than lidocaine pretreatment, may be a reasonable analgesic alternative for painful injections. IMPLICATIONS: Metoclopramide, rather than lidocaine pretreatment, may be a reasonable analgesic alternative to decrease pain from a diazepam injection, especially when there is a medical condition in which lidocaine should be used very cautiously.