Central Pain Research Articles

A vagus nerve dominant tetra-synaptic ascending pathway for gastric pain processing.

Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS-LPB-PVT-PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS-LPB-PVT-PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain.

Active Neurodynamic Technique at Home in Patients with Knee Osteoarthritis: An Open Single Arm Clinical Trial

Background and Objectives: Knee osteoarthritis (KO) stands as the third leading cause of disability among the elderly, causing pain, reduced quality of life, and decreased functionality. The objective of this study is to assess the effects of an active neurodynamic technique programme at home on pain, quality of life, and function among individuals with KO. Materials and Methods: Thirty-five participants (69.7% women) aged ≥50 years with KO (Kellgren–Lawrence grades I–II) performed a femoral nerve mobilization programme at home for 6–8 weeks (20 repetitions per day). Pain intensity, using the numerical rating scale (NRS), pressure pain thresholds (PPTs), central sensitization inventory (CSI), temporal assessment, pain modulation, Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 12-item Short Form Survey questionnaire (SF-12) were collected before, after the intervention, and at one, three, six, and twelve months. Results: Participants improved significantly in pain (p < 0.05), with the improvement maintained throughout the follow-up in the NRS and for at least one month in the PPT. There were also statistically significant (p < 0.05) improvements in all subscales of the KOOS, which were maintained throughout the follow-up. Improvements were also found in the CSI and CPM. Conclusions: A home-based active neurodynamic programme for the femoral nerve has been demonstrated to yield positive effects on pain and function in patients with KO.

Abstract 4135303: Acute Pericarditis Secondary to Secukinumab Therapy

Background: Pericarditis is the most common pericardial disease worldwide and has a high recurrence rate of 15-30%. It is primarily idiopathic but can arise from infectious and non-infectious causes; drug related cases are rare. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody used for treating psoriasis, has been identified through the FDA Adverse Event Reporting System as potentially inducing pericarditis, though literature is scant. We report a case of acute pericarditis related to secukinumab use. Case presentation: A 28-year-old male with history of psoriasis on secukinumab therapy presented with sharp, central chest pain, and progressive shortness of breath for 3 weeks. He was evaluated for similar chest pain 3 weeks prior; CT chest showed small pericardial effusion and he was managed with analgesics without improvement. This admission, he had tachycardia, and ECG showed sinus rhythm with diffuse ST elevation and PR depression (Figure 1A). Troponin I levels were normal and inflammatory markers were elevated. Transthoracic echocardiogram (TTE) revealed a large pericardial effusion without tamponade physiology (Figure 1B). CT chest confirmed large pericardial effusion, increased in size compared to CT done 3 weeks prior (Figure 2). He was diagnosed with pericarditis and started on ibuprofen and colchicine which improved his symptoms. Search for viral etiology including testing for COVID, influenza A and B, RSV, hepatitis and HIV were negative. Immunological workup for ANA and rheumatoid factor was negative. Thus, secukinumab was thought to be the likely culprit. Follow-up TTE in 3 months showed resolution of pericardial effusion. Conclusion: This case underscores the importance of considering medication-induced pericarditis in patients presenting with typical symptoms, especially when on treatment with drugs like secukinumab. Given the growing evidence from pharmacovigilance databases and the severe potential outcomes of untreated pericarditis, clinicians should maintain vigilance for such adverse effects. Further research is warranted to clarify the mechanisms by which secukinumab may contribute to pericardial inflammation in order to optimize management strategies in affected patients.

New ways to repurpose salmeterol in an animal model of fibromyalgia.

Fibromyalgia (FM) is a syndrome of pervasive chronic pain accompanied by low mood, sleep disorders, and cognitive decline. The dysfunction of central pain processing systems along with neurotransmitter disturbances are possible contributing mechanisms. Genetic polymorphism of the 𝛽2 adrenergic receptors is reported in FM patients. It is reported that chronic β2 agonists administration is effective for neuropathic pain alleviation. No current information, however, exists on their potential to alleviate nociplastic pain, such as FM. Therefore, the purpose of the current study is to examine salmeterol's potential antiallodynic effects in experimentally produced FM and explore some of the possible contributing mechanisms. Thirty rats are allocated into three groups (n = 10): a normal group, a reserpine group that received reserpine (1 mg/kg; s.c.) for 3 days, and a reserpine + salmeterol group that received salmeterol (1 mg/kg; i.p.) for 21 consecutive days following last reserpine injection. Reserpine administration resulted in behavioral and biochemical changes consistent with FM, including thermal and mechanical hyperalgesia, depressive behavior, and motor incoordination. This is coupled with disturbed spinal monoamine levels, depressed cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, disturbed mitochondrial function/dynamics, and compromised blood-nerve barrier integrity. Treatment with salmeterol conceivably reversed these effects. β2 receptor agonists such as salmeterol could be regarded as a promising strategy for the management of FM.

Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder triggered by herpes zoster: a case report and literature review.

This paper presents the case of a 45-year-old woman who developed aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) approximately 6 weeks after a herpes zoster infection. Her initial symptoms included area postrema syndrome, which was marked by persistent nausea, vomiting, and belching. This report also provides a summary of the demographic and clinical features, disease progression, magnetic resonance imaging findings, cerebrospinal fluid analysis, treatment plans, and recovery outcomes of 11 patients-including this case and 10 others reported in the literature since 2008-who developed AQP4 antibody-positive NMOSD following herpes zoster infection. This review aims to improve clinicians' understanding of the characteristics, treatment, and prognosis of this disease. It also highlights the importance for pain management specialists to consider central pain and use the MIDNIGHTS or VINDψCATE mnemonic devices to systematically consider the differential diagnoses of a patient's new pain symptoms.

Do measures of central sensitization relate to movement-evoked pain in people with chronic low back pain? A longitudinal prospective study

BackgroundOne of the most frequent complaints among people with musculoskeletal pain is pain during physical activity, commonly referred to as movement-evoked pain. It is suggested to be associated with quantitative sensory testing measures of central pain process in individuals with musculoskeletal pain. ObjectiveTo investigate the predictive association between movement-evoked pain scores and measures of central sensitization in patients with chronic nonspecific low back pain. The secondary aim was to determine whether changes in movement-evoked pain scores are associated with changes in measures of central sensitization. MethodsIn this longitudinal prospective study, 50 participants with chronic low back pain were included. Pain pressure thresholds, temporal summation of pain, descending pain modulation, and the central sensitization index were assessed as measures of central sensitization. Movement-evoked pain was evaluated using the Back Performance Scale and a 5-minute walk test. ResultsMeasures of central sensitization, specifically pressure pain thresholds and temporal summation, demonstrated predictive associations with movement-evoked pain measures. In response to treatment, improvements in movement-evoked pain were associated with improvements in measures of central sensitization (i.e., pressure pain thresholds and temporal summation) and improved pressure pain thresholds in the plantar toe significantly predict movement-evoked pain measures experienced during the 5-minute walk test. ConclusionsThese results imply that movement-evoked pain is related to processes related to central modulation of pain in patients with nonspecific chronic low back pain.

Promoting multidisciplinary pain management in low- and middle-income countries—challenges and achievements

Abstract The burden of pain in low- and middle income countries (LMICs) is high and expected to rise further with their ageing populations. Multidisciplinary pain management approaches based on the biopsychosocial model of pain have been shown to be effective in reducing pain-related distress and disability, but these approaches are still lacking in many LMICs due to various factors, including low levels of awareness about the role of multidisciplinary pain clinics, lack of prioritisation for pain services, and lack of healthcare professionals trained in pain management. The International Association for the Study of Pain (IASP) has several educational programs to promote multidisciplinary pain management in LMICs, in the form of education grants, pain fellowships, pain camps and, most recently, the development of a Multidisciplinary Pain Centre Toolkit. This article describes the various educational programs, focusing on Southeast Asia, that demonstrate how targeted educational programs which include skills training, follow-up and mentorship, can translate into the formation of new multidisciplinary pain management services in settings with limited resources.

Prescription time trends in patients with high-impact chronic pain: A National Patient Registry Study.

High-impact chronic pain (HICP), defined as chronic pain with a significant impact on daily function, affects approximately 8% of the Western population. In Denmark, HICP still remains to be described at the population level. Some patients with HICP are referred to the Danish pain centres, where they are registered with a procedural code. We conducted a nationwide registry-based study of all Danish patients registered with a visit to a pain centre from January 2005 to March 2022, to explore time trends in the prescription of analgesics and sedatives in this HICP subpopulation. Furthermore, data on socioeconomics and hospital diagnoses are reported. We used data from the Central Person Registry, the Danish National Patient Registry, the Danish National Prescription Registry, combined with data on socioeconomic information from Statistics Denmark. Data was collected on prescriptions 3 months before the first visit to a pain centre. Prescriptions were stratified into five calendar periods: before 2011, 2011-2013, 2014-2016, 2017-2019, and 2020-2022. We identified 66,577 patients referred to a pain centre. Over 15 years, prescriptions before referral declined for opioids (from 53.2% to 31.7%), NSAIDs (from 28.3% to 23.5%), antidepressants (from 20.5% to 16.8%), anxiolytics (from 12.3% to 3.2%), and sleep medication (from 15.8% to 7.6%). In contrast, prescriptions increased for paracetamol (from 31.1% to 48.9%) and gabapentinoids (from 19.2% to 27.7%). In patients with HICP visiting Danish pain centres, prescriptions before referral decreased for opioids over 15 years, with a simultaneously increased prescription of gabapentinoids (gabapentin and pregabalin). This nationwide study of 66,577 Danish patients with high-impact chronic pain reveals a significant decrease in filled opioid prescriptions over the past 15 years, with a simultaneous rise in gabapentinoid use before referral to pain centres. These findings suggest a shift in clinical practice towards alternative pain management strategies. The study underscores the need for continued research into the long-term effects of these changes and their impact on patient outcomes.

Low ambient temperature and incident myocardial infarction with or without obstructive coronary arteries: a Chinese nationwide study.

Although non-optimum ambient temperature is a major non-traditional risk factor for acute myocardial infarction, there is no prior knowledge on whether non-optimum ambient temperature could differentially affect myocardial infarction with obstructive coronary artery disease (MI-CAD) and myocardial infarction with non-obstructive coronary arteries (MINOCA). Using the Chinese Cardiovascular Association database-Chest Pain Center Registry, a nationwide, time-stratified, case-crossover investigation was conducted from 2015 to 2021. Meteorological data were obtained from an established satellite-based model, and daily exposures were assigned according to the onset of myocardial infarction in each patient. A conditional logistic regression model combined with distributed lag non-linear models (10 days) was used to estimate the exposure-response relationships. A total of 83 784 MINOCA patients and 918 730 MI-CAD patients were included. The risk of MINOCA and MI-CAD associated with low temperature occurred at lag 2 day and lasted to 1 week. Extremely low temperature was associated with a substantially greater odds ratio (OR) of MINOCA [OR 1.58, 95% confidence interval (CI) 1.31-1.90] than MI-CAD (unmatched: OR 1.32, 95% CI 1.23-1.43; equally matched by age and sex: OR 1.25, 95% CI 1.04-1.50), compared with the corresponding reference temperatures (30°C, 35°C, and 30°C). Stronger associations were observed for patients who were aged ≥65 years, female, or resided in the south. There was no significant difference for the impacts of high temperature on MINOCA and MI-CAD. This nationwide study highlights the particular susceptibility of MINOCA patients to ambient low temperature compared with that of MI-CAD patients.

Non-surgical spinal cord infarction: case series & long-term follow-up of functional outcome

IntroductionSpinal cord infarction is a rare but often devastating disorder. The pathogenesis of most non-surgical cases involves atherothrombosis and treatment with anticoagulation and antiplatelet agents may be indicated. Functional recovery in most cases is poor. We describe five cases of spinal cord infarction and provide details on their functional outcomes after long-term (>10 years) follow-up.Case presentationA 28-year-old female presented at 16 weeks gestation with chest and back pain and paraesthesia in her fingers. Magnetic resonance imaging on admission revealed a spinal cord lesion extending from C5-T8. She was treated with anticoagulation and rehabilitation. Six years following presentation she was able to return to work. A 42-year-old male experiencing central chest pain and leg weakness was initially diagnosed as having acute coronary syndrome. Following discharge, he was re-admitted with urinary retention and leg weakness. Magnetic resonance imaging revealed a spinal cord lesion extending from T4 to T7. He was treated with anticoagulation, and eight months following presentation he regained full muscle strength but required intermittent self-catherisation. Three further cases are described.DiscussionThe aetiology of non-surgical spinal cord infarction is not always evident, but is commonly associated with atherothrombosis. There are often delays in making a diagnosis, but early recognition and prompt treatment of spinal cord infarction is essential. Long-term functional outcomes are often poor and typically reflect the severity of initial presentation. This case series is unique as it has one of the longest follow-up periods described in the literature.

Bedside Neuromodulation of Persistent Pain and Allodynia with Caloric Vestibular Stimulation.

Caloric vestibular stimulation (CVS) is a well-established neurological diagnostic technique that also induces many phenomenological modulations, including reductions in phantom limb pain (PLP), spinal cord injury pain (SCIP), and central post-stroke pain. We aimed to assess in a variety of persistent pain (PP) conditions (i) short-term pain modulation by CVS relative to a forehead ice pack cold-arousal control procedure and (ii) the duration and repeatability of CVS modulations. The tolerability of CVS was also assessed and has been reported separately. We conducted a convenience-based non-randomised single-blinded placebo-controlled study. Thirty-eight PP patients were assessed (PLP, n = 8; SCIP, n = 12; complex regional pain syndrome, CRPS, n = 14; non-specific PP, n = 4). Patients underwent 1-3 separate-day sessions of iced-water right-ear CVS. All but four also underwent the ice pack procedure. Analyses used patient-reported numerical rating scale pain intensity (NRS-PI) scores for pain and allodynia. Across all groups, NRS-PI for pain was significantly lower within 30 min post-CVS than post-ice pack (p < 0.01). Average reductions were 24.8% (CVS) and 6.4% (ice pack). CRPS appeared most responsive to CVS, while PLP and SCIP responses were less than expected from previous reports. The strongest CVS pain reductions lasted hours to over three weeks. CVS also induced substantial reductions in allodynia in three of nine allodynic CRPS patients, lasting 24 h to 1 month. As reported elsewhere, only one patient experienced emesis and CVS was widely rated by patients as a tolerable PP management intervention. Although these results require interpretative caution, CVS was found to modulate pain relative to an ice pack control. CVS also modulated allodynia in some cases. CVS should be examined for pain management efficacy using randomised controlled trials.

Ostial left main disease tackled with a percutaneous coronary intervention using a second-generation drug-eluting stent: A case report

Abstract: The hospital emergency admitted a middle-aged male who had previously undergone stenting in the left anterior descending (LAD) and right coronary arteries due to severe central chest pain radiating to both arms. A two-dimensional color Doppler echocardiogram showed septal hypokinesia, and coronary angiography showed a 70% ostial left main (LM) stenosis. The LAD coronary artery had a patent stent, but the mid-right coronary artery had a totally occluded stent. The chest pain increased during coronary angiography, and the patient consented to percutaneous coronary intervention (PCI) with a second-generation drug-eluting stent. The patient was discharged in a stable condition. The evolution and the current approach of PCI compared to coronary artery bypass grafting surgery for LM coronary disease based on randomized trials are discussed.

Low-dose methadone added to another opioid for cancer pain: a multicentre prospective study

ContextThe use of methadone for cancer pain management is gaining wider acceptance. However, switching to methadone treatment can still pose challenges. Consequently, there is ongoing development of its use in low doses in combination with other opioids, despite a lack of clinical evidence regarding its efficacy and safety.ObjectivesThis study aimed to evaluate the efficacy and tolerability of low-dose methadone in combination with another opioid in patients with moderate-to-severe cancer-related pain in a clinical setting.Patients and methodsThis was a prospective, open-label study conducted in 19 pain and/or palliative care centres treating patients with cancer-related pain. Pain intensity, patients' global impression of change, and adverse effects were assessed on day 7 and day 14. The main outcome measure was the proportion of responders.ResultsThe study included 92 patients. The daily dose of methadone was 3 [3–6] mg at baseline, 9 [4–10] mg on day 7 and 10 [6–15] mg on day 14. The NRS pain ratings significantly decreased from 7 [6–8] at baseline to 5 [3–6] on visit 2 (p < .0001) and 4 [3–6] on visit 3 (p < .0001). Similarly, the VRS pain ratings decreased from 3 [3–3] at baseline to 2 [2–3] on visit 2 (p = 0.026) and 2 [1–3] (p < 0.001) on visit 3. At Visits 1 and 2, half of the patients were considered Responders. Of those responders, 73.5% were High-Responders at Visit 1 and 58.7% were High-Responders at Visit 2. No adverse events related to the risk of QT prolongation, overdose, or drug interactions were reported.ConclusionFor patients experiencing moderate to severe cancer-related pain despite initial opioid treatment, our study found that low-dose methadone, when used in combination with another opioid, was both safe and effective. This supports the use of methadone as an adjunct to opioid-based treatment for cancer pain.

Interpretation of a clinical practice guideline on the management of chronic pain associated with temporomandibular joint disorders

Temporomandibular disorders (TMD) are a heterogeneous group of diseases that affect the temporomandibular joint, chewing muscle system, dental occlusion, and even various structures throughout the body, with significant characteristics of biological-psychological-social pattern. TMD related chronic pain, as the most important clinical symptom, can result in negative emotions seriously affecting patients' quality of life and physical and mental health. Although a variety of therapies have been previously reported to treat TMD related chronic pain, there is a lack of widely recognized therapies. Professor Jason W Busse (from Michael G DeGroote National Pain Centre, McMaster University, Hamilton ON, Canada) took the lead and collaborated with multiple internationally renowned schools/hospitals of stomatology to develop an international consensus on the management of chronic pain associated with TMD, a clinical practice guideline, which took two years and was published in December 15th, 2023 in a global top journal of clinical research The British Medical Journal. This clinical practice guideline explored the comparative effectiveness of available therapies for chronic pain associated with TMD, conditionally recommended the specific intervention for different treatment or pain relief, proposed a comprehensive, agreed, and standardized clinical practice guideline. This present article describes the methodology and key elements of the clinical practice guideline to help clinicians fully understand and appropriately apply this guidance, which could provide the references for clinical practice of TMD associated chronic pain in China.

The role of environmental sensitivity, traumatic experiences, defense mechanisms and mental pain on central sensitivity: testing a path analysis model in chronic headache on quality of life.

Central pain sensitivity (CS) is defined as an increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold inputs. The main aim of this paper is to investigate if and how specific psychological constructs are related with CS burden in patients with chronic headache (CH). Specifically, research question 1 explores the association of temperament, personality, childhood adversities, defense mechanisms and mental pain with CS burden. Research question 2 aims to test the role of the best predictors of CS burden in affecting the quality of life (QoL) using path analysis. A total of 508 women with CH completed a psycho-diagnostic survey. Results showed that higher levels of low sensory threshold (β = 0.200), bodily threat traumatic experiences (β = 0.156), neurotic defenses (β = 0.109) and mental pain (β = 0.343) emerged as the best predictors of higher CS burden. The model presented demonstrated a satisfactory fit (GFI = 0.984; NFI = 0.966; CFI = 0.979; RMSEA = 0.056 [95% CI 0.028-0.085]) with large and medium effect sizes on physical (-0.654) and psychological QoL (-0.246). The study showed a key role of psychological dimensions in CS burden levels and their relationships with QoL in CH patients. From a clinical perspective, these results suggest the importance of evaluating the level of CS burden during the clinical assessment for chronic pain conditions such as CH, since it may contribute to guide patients to tailored psychological and medical treatments, thereby saving time and costs on diagnostic procedures for chronic pain.

Effect of continuous improvement of standardized construction of China Chest Pain Center on treatment time and mortality of acute ST-segment elevation myocardial infarction: A population-based study.

Standardized construction of China Chest Pain Center improves outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI). A total 778 patients with a definite diagnosis of STEMI who underwent percutaneous coronary intervention (PCI) in our hospital from March 2017 to November 2022 were selected. Among them, 194 patients admitted from March 2017 to December 2019 were included as the pre-continuous improvement period (control group), and 584 patients admitted from January 2020 to November 2022 were included as the continuous improvement period (study group). Major quality control indicators were compared between the 2 groups. In continuous improvement period, the time of electrocardiograph (ECG) diagnosis, time of dual antiplatelet drug administration, troponin I return time, catheter activation time, and door to wire (D2W) were all significantly shorter than those in the pre-continuous improvement period (P < .05). The reperfusion rate of patients in the continuous improvement period was 98.12%, which was significantly higher than that in the pre-continuous improvement period (92.78%; P < .001). The mortality rate of STEMI patients in continuous improvement period was 3.42%, lower than 4.64% in the pre-continuous improvement period with no statistical difference (P = .439). Age, previous history of coronary artery disease, and high Killip class (Killip III-IV) were derived as independent risk factors for death by logistic regression analysis (OR＞1, P < .05). Continuous improvement of the chest pain center can effectively shorten the treatment time of STEMI patients, improve the reperfusion rate, and improve myocardial blood supply by restoring TIMI blood flow as early as possible.

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.

Usefulness of Mirogabalin in Central Neuropathic Pain After Stroke: Post Hoc Analysis of a Phase3 Study by Stroke Type and Location.

Central post-stroke pain (CPSP) is a common type of central neuropathic pain (CNeP) that can occur following the onset of stroke. The oral gabapentinoid mirogabalin besylate (mirogabalin) is a selective α2δ ligand that is effective for the treatment of CNeP, including CPSP. However, it is unknown whether the analgesic effect of mirogabalin on CPSP varies in patients with different background factors. This was a post hoc subgroup analysis of a multinational, open-label, long-term phase3 study of mirogabalin for the treatment of CNeP conducted between March 2019 and December 2020. Data from patients with CPSP were stratified by type of stroke (ischemic or hemorrhagic), stroke location (thalamus, putamen, brainstem, or other), presence/absence of motor weakness, median time since stroke (≥ 59 or < 59months), and median duration of CPSP (≥ 55.5 or < 55.5months). Efficacy was assessed with the short-form McGill Pain Questionnaire (SF-MPQ), and treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were recorded. This subanalysis included all 94 patients with CPSP from the phase3 study; all were Japanese, and the mean age was 65.3years. The least squares mean change [95% confidence interval] in SF-MPQ visual analog scale (VAS) score from baseline at week52 (last observation carried forward) was - 17.0 [- 22.1, - 11.9] mm. Among the subgroups, least squares mean changes in SF-MPQ VAS scores were not different. Most TEAEs were mild or moderate; severe TEAEs occurred in six patients (6.4%). Somnolence (25.5%), peripheral edema (13.8%), dizziness (11.7%), and weight gain (6.4%) were the most common ADRs, and the types and frequencies of ADRs were similar among subgroups. Mirogabalin was generally effective and well tolerated in patients with CPSP, regardless of background factors such as stroke type or location, presence/absence of motor weakness, time since stroke, and duration of CPSP. Trial registration number NCT03901352.

Peripheral Neuropathic Pain.

This article synthesizes current knowledge on neuropathic pain, with a brief review of mechanisms, diagnostic approaches, and treatment strategies to help neurologists provide effective and individualized care for patients with this complex condition. The most promising developments in peripheral neuropathic pain are related to the molecular biology of the peripheral nervous system. Systematic molecular and genetic analyses of peripheral nerve terminals and dorsal root ganglia have advanced our understanding of the genetics of function and disease of peripheral nerves, as well as their physiology and clinical manifestations. Peripheral neuropathic pain, similar to central neuropathic pain, is primarily influenced by the biology and pathophysiology of the underlying structures, peripheral sensory nerves, and their central pathways. The clinical course is widely variable in sensory symptoms and intensities, natural history, and response to treatments.

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.