Severe Neuropathic Pain Research Articles

Neurological features of Noonan syndrome and related RASopathies: Pain and nerve enlargement characterized by nerve ultrasound.

This study aimed to assess the nature of peripheral nervous system (PNS) involvement in three patients with Noonan syndrome (NS) or NS with multiple lentigines (NSML) as a related RASopathy, presenting primary with intractable neuropathic pain. We studied three unrelated adult patients with severe neuropathic pain and muscle weakness of the limbs. Nerve conduction studies and needle electromyography (EMG) were performed and PNS involvement was assessed by nerve ultrasound imaging, complemented with spinal magnetic resonance imaging (MRI) for the evaluation of proximal nerve segments. Targeted whole-exome sequencing analysis was performed when the diagnosis of NS was suspected. Two patients showed a PTPN11-related dominant and one a LZTR1-related recessive NS or NSML phenotype. The nature of PNS involvement was documented using nerve ultrasound and MRI, showing generalized or multifocal thickening of nerve roots, plexuses and peripheral nerves in all three patients. Nerve imaging using ultrasound and MRI aids in further detailing the nature of neuropathic pain and nerve hypertrophy in patients with NS. This study underlines the relevance of nerve ultrasound in neuropathies and pain syndromes. A NS diagnosis should not be overlooked in longstanding, unexplained neuropathic pain syndromes, with or without muscular weakness. Nerve ultrasound studies can help raise the suspicion for this relatively prevalent inherited multisystem disorder, which is still rather unknown among neurologists, particularly when other potential syndromic features are inconspicuous.

Treatment Analysis of Patients Followed up With Postherpetic Neuralgia in Nothern Cyprus.

Background:Postherpetic neuralgia (PHN) is a frequent complication of herpes zoster (HZ). Treatment of this chronic pain syndrome and results are often not clear. Tricyclic antidepressants, gabapentinoids and potent opioids are first-line treatments and are highly effective, but their use is limited due to adverse effects that may occur in elderly patients with significant medical comorbidities or interaction due to multiple drug use. There are no head-to-head comparisons of non medical treatments. Dry needling appears comparable to conventional physical therapy for treating PHN.Objective:Our aim is to determine the incidence of PHN in our population and to compare the treatments in patients with postherpetic neuralgia.Methods:A search for HZ and PHN was conducted in a general practice research database, comprising 2 general practices (dermatologist and physiatrist) and representing 5600 people. We analyzed a retrospective 37 case with PNH of 170 herpes zoster patient admmited to the dermatology and physical therapy and rehabilitation outpatient clinic between October 2018 and October 2020. Dry needling and physical therapy methods applied in addition to medical treatment in PHN treatment were compared.Results:In patients with postherpetic neuralgia, both dry needling therapy group and physical therapy group LANSS scores decreased significantly in the first week and in the third week compared to baseline. Dry needling therapy group has also similar results in VAS scores in the first and third week. But in physical therapy group, the VAS score did not show a significant decrease in the first week compared to the baseline, but it decreased significantly in the third week.Conclusion:PHN is a complex, difficult to treat and severe neuropathic pain that affects patients’ daily function and quality of life. Various agents and methods are available to relieve the symptoms of PHN. This study shows as both physical therapy and dry needling therapy are effective treatment for postherpetic nevralgia..

Abstract No. : ABS2262: Ultrasound guided continuous stellate ganglion block in peripheral vascular disease of upper limb - A case series

Background and Aims:Stellate ganglion block relieves pain and improves perfusion in peripheral vascular disease(PVD) of upper limbs. Single shot stellate ganglion block often provides only short-term relief and repeated blocks are associated with tissue or neural damage and infections. Non-availability/affordability limits the use of thermal radiofrequency nerve ablation of the stellate ganglion.We report our experience of managing 46 cases of PVD of upper limb with continuous stellate ganglion block(CSGB).Methods:Six cases of PVD of left upper limb who presented with severe ischemic neuropathic pain and blackish discoloration of fingers were treated with ultrasound guided CSGB with infusion of 0.125% of bupivacaine at 5ml per hour for 5 days. All patients were assessed for intensity of pain using numerical rating scale (NRS), change of colour and peripheral pulsations before the procedure and 2, 4, 12 and 24 weeks after the procedure.Results:All the patients reported significant reduction in NRS scores, improvement in skin colour, healing of gangrenous lesions and return of peripheral pulsations at follow up visits.Conclusion:Continuous catheter infusion not only provides more sustained pain relief and emerges as a cost effective option in improving perfusion and aid wound healing.

Comparison of the Effectiveness and Tolerability of Nabiximols (THC:CBD) Oromucosal Spray versus Oral Dronabinol (THC) as Add-on Treatment for Severe Neuropathic Pain in Real-World Clinical Practice: Retrospective Analysis of the German Pain e-Registry.

PurposeTo compare the effectiveness and tolerability of add-on treatment with nabiximols (NBX: delta-9-tetrahydrocannabinol: cannabidiol) oromucosal spray or oral dronabinol (DRO: synthetic tetrahydrocannabinol) in patients with severe neuropathic pain poorly responsive to established treatments.MethodsAn analysis was conducted of anonymized, propensity score-matched real-world data from the German Pain e-Registry, using a sequential non-inferiority superiority approach, for adult outpatients with neuropathic pain who had initiated treatment with NBX or DRO between 10 March 2017 and 31 December 2019. The primary effectiveness variable was percent change from baseline in a 9-factor aggregated symptom relief (ASR-9) score, a composite index of nine distinct pain- and health-related parameters assessed using validated patient-reported instruments. Safety was assessed by the incidence of physician-confirmed treatment-related adverse events (TRAEs), and TRAEs leading to discontinuation.ResultsPropensity score-matched data were analyzed for 337 patients treated with NBX and 337 patients treated with DRO. Mean (standard deviation) THC dose over the 24-week evaluation period was 16.6 (6.5) mg for NBX and 17.2 (7.6) mg for DRO (p<0.001). Median (standard error) improvement relative to baseline in the ASR-9 composite score was 55.4% (0.5) for NBX and 40.5% (0.5) for DRO (least squares mean difference, 14.0 (0.7), 95% confidence interval 12.6–15.4; p<0.001), and incidences of TRAEs (21.1 vs 35%) and TRAE-related discontinuations (5.9 vs 14.8%) were significantly lower with NBX than DRO (p<0.001 for both), collectively indicating pre-specified non-inferiority and superiority of NBX. More NBX- than DRO-treated patients discontinued non-cannabinoid background pain medications and rescue analgesics, especially opioid analgesics (p<0.001 for both).ConclusionAdd-on treatment with cannabinoids is effective for treatment of severe neuropathic pain with inadequate response to established treatments. In daily practice, NBX had superior effectiveness and tolerability compared to DRO. The results emphasize the importance of combining CBD with THC in this patient population.

A Fully Implantable Miniaturized Liquid Crystal Polymer (LCP)-Based Spinal Cord Stimulator for Pain Control.

Spinal cord stimulation is a therapy to treat the severe neuropathic pain by suppressing the pain signal via electrical stimulation of the spinal cord. The conventional metal packaged and battery-operated implantable pulse generator (IPG) produces electrical pulses to stimulate the spinal cord. Despite its stable operation after implantation, the implantation site is limited due to its bulky size and heavy weight. Wireless communications including wireless power charging is also restricted, which is mainly attributed to the electromagnetic shielding of the metal package. To overcome these limitations, here, we developed a fully implantable miniaturized spinal cord stimulator based on a biocompatible liquid crystal polymer (LCP). The fabrication of electrode arrays in the LCP substrate and monolithically encapsulating the circuitries using LCP packaging reduces the weight (0.4 g) and the size (the width, length, and thickness are 25.3, 9.3, and 1.9 mm, respectively). An inductive link was utilized to wirelessly transfer the power and the data to implanted circuitries to generate the stimulus pulse. Prior to implantation of the device, operation of the pulse generator was evaluated, and characteristics of stimulation electrode such as an electrochemical impedance spectroscopy (EIS) were measured. The LCP-based spinal cord stimulator was implanted into the spared nerve injury rat model. The degree of pain suppression upon spinal cord stimulation was assessed via the Von Frey test where the mechanical stimulation threshold was evaluated by monitoring the paw withdrawal responses. With no spinal cord stimulation, the mechanical stimulation threshold was observed as 1.47 ± 0.623 g, whereas the stimulation threshold was increased to 12.7 ± 4.00 g after spinal cord stimulation, confirming the efficacy of pain suppression via electrical stimulation of the spinal cord. This LCP-based spinal cord stimulator opens new avenues for the development of a miniaturized but still effective spinal cord stimulator.

The Up-regulation of TNF-α Maintains Trigeminal Neuralgia by Modulating MAPKs Phosphorylation and BKCa Channels in Trigeminal Nucleus Caudalis.

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous available medical interventions, the therapeutic effects are not ideal. To control the pain attacks, the need for more contemporary drugs continues to be a real challenge. Our previous study reported that Ca2+-activated K+ channels (BKCa) channels modulated by mitogen-activated protein kinases (MAPKs) in the trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some research studies demonstrated that inflammatory cytokine tumor necrosis factor alpha (TNF-α) could promote neuropathic pain. Meanwhile, the trigeminal nucleus caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is responsible for processing sensory and pain signals from the peripheral orofacial area. Thus, this study is aimed to further investigate whether TNF-α and MAPKs phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BKCa channels. The results showed that TNF-α of the TNC region is upregulated significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) rats model, which displayed persistent facial mechanical allodynia. The normal rats with target injection of exogenous TNF-α to the fourth brain ventricle behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold decreased clearly. Meanwhile, the exogenous TNF-α increased the action potential frequency and reduced the BKCa currents of TNC neurons significantly, which could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI model rats, respectively. Taken together, our work suggests that the upregulation of TNF-α in the TNC region would cause the increase of MAPKs phosphorylation and then the negative regulation of BKCa channels, resulting in the TN.

Extracellular ATP and cAMP signaling promote Piezo2-dependent mechanical allodynia after trigeminal nerve compression injury.

Trigeminal neuralgia (TN) is a type of severe paroxysmal neuropathic pain commonly triggered by mild mechanical stimulation in the orofacial area. Piezo2, a mechanically gated ion channel that mediates tactile allodynia in neuropathic pain, can be potentiated by a cyclic adenosine monophosphate (cAMP)-dependent signaling pathway that involves the exchange protein directly activated by cAMP 1 (Epac1). To study whether Piezo2-mediated mechanotransduction contributes to peripheral sensitization in a rat model of TN after trigeminal nerve compression injury, the expression of Piezo2 and activation of cAMP signal-related molecules in the trigeminal ganglion (TG) were detected. Changes in purinergic P2 receptors in the TG were also studied by RNA-seq. The expression of Piezo2, cAMP, and Epac1 in the TG of the TN animals increased after chronic compression of the trigeminal nerve root (CCT) for 21days, but Piezo2 knockdown by shRNA in the TG attenuated orofacial mechanical allodynia. Purinergic P2 receptors P2X4, P2X7, P2Y1, and P2Y2 were significantly up-regulated after CCT injury. In vitro, Piezo2 expression in TG neurons was significantly increased by exogenous adenosine 5'-triphosphate (ATP) and Ca2+ ionophore ionomycin. ATP pre-treated TG neurons displayed elevated [Ca2+ ]i and faster increase in responding to blockage of Na+ /Ca2+ exchanger by KB-R7943. Furthermore, mechanical stimulation of cultured TG neurons led to sustained elevation in [Ca2+ ]i in ATP pre-treated TG neurons, which is much less in naïve TG neurons, or is significantly reduced by Piezo2 inhibitor GsMTx4. These results indicated a pivotal role of Piezo2 in peripheral mechanical allodynia in the rat CCT model. Extracellular ATP, Ca2+ influx, and the cAMP-to-Epac1 signaling pathway synergistically contribute to the pathogenesis and the persistence of mechanical allodynia.

Improvement of pain management in a comprehensive cancer center: a comparison of two cross-sectional studies 8years apart.

In 2011, a multidisciplinary palliative team (MPT) was established at Rigshospitalet (DK) and a cross-sectional study in inpatients was carried out at the Departments of Oncology and Hematology. High symptom burden, high prevalence of pain (64%), and insufficient analgesic treatment were demonstrated. In 2019, a similar study was carried out. This study compares prevalence of symptoms including pain and analyzes analgesic treatment of adult in-patients in a comprehensive cancer center. Two cross-sectional studies (May-Jun 2011; Feb-Sep 2019). malignant diseases, age ≥ 18 y, able to understand Danish. EORTC QLQ-C30 and Brief Pain Inventory (BPI) were applied. A total of 134 and 183 inpatients were included in 2011 and 2019, respectively. Differences in the two populations were seen; in 2019 more patients had advanced disease (P = 0.0096), lower performance status (P = 0.0028), and a palliative treatment plan (P = 0.0034). The prevalence of impairments and symptoms was high and similar in the 2years with exception of severe pain (P = 0.0143) and neuropathic pain (P < 0.0001) which increased in 2019. Moreover, pain relief significantly improved, and significantly fewer patients with pain were left untreated. Significant increase in opioid and adjuvant analgesic prescription in 2019. An overall unchanged high symptom burden was observed. However, improvement of pain management was observed in 2019. The establishment of a MPT may possibly have contributed to improved pain management.

Multimodal Spinal Cord Mapping during Spinal Cord Stimulator Placement: Technical Note

ABSTRACT Spinal cord stimulation is used to treat patients with severe neuropathic pain and other forms of debilitating back pain. Spinal cord stimulators (SCS) can either be placed under sedation or general anesthesia (GA). This study evaluated the utility of neurogenic evoked potentials in enabling multimodal spinal cord mapping (MSCM) for the placement of SCSs under GA. The goal of our MSCM paradigm, which integrated recordings from multiple antidromic and orthodromic generators, was to enable the use of precise neuromonitoring techniques, typically used for localizing the midline of the dorsal spinal cord in intramedullary tumor cases, for the safe placement of SCSs. Two distinct modalities were incorporated - orthodromic responses from the somatosensory cortex (Cp3-Cp4 cancellation) and antidromic stimulation via the SCS which resulted in compound nerve action potentials of the extremities. In addition, two incidental findings were made. First, our results suggest that previous investigations may have incorrectly identified compound muscle action potentials as compound nerve action potentials. Additionally, anti D-wave responses, that are theorized to be the equivalent of a D-wave, were observed. This manuscript describes the first use of MSCM, which will ultimately provide neurophysiologists more information during SCS implantation, enabling them to confirm midline placement more confidently. MSCM also allows the application of techniques typically used in spinal cord tumors, allowing the neurophysiologist to maintain proficiency with these techniques on more common procedures. The parallel collection of several sources of data will allow for future studies that better define which mapping methods are the most accurate.

Neuropathic pain as a predictor of neurological disorders regression in patients with spinal cord traumatic injury

Background. Neuropathic pain is one of the principal secondary complications of spinal cord injury. The biological role of neuropathic pain has not been established yet. This type of pain is formed directly in the area of the spinal cord injury; therefore, it can be assumed that its intensity may characterize both degenerative and reparative processes. The aim of this work is to assess the possible relationship between the intensity of neuropathic pain in patients with spinal cord injury at cervical subaxial spine and the dynamics of neurological disorder regression. Materials and methods. We have performed a retrospective analysis of patients referred to outpatient department of the Romodanov Neurosurgery Institute of National Academy of Medical Sciences of Ukraine in the period from 2010 to 2020 after a surgical treatment of subaxial cervical spine traumatic injury. The extent of neurological disorders and the intensity of neuropathic pain were assessed within 5–7 and 11–13 months after surgery. Results. All 102 patients selected for analysis were divided into three groups depending on the intensity of the registered pain sensations: 1) absence of constant pain sensations — 19.6 % of subjects, 2)moderate pain— 56.9 %, 3) severe neuropathic pain — 23.5 %. In the first group, the regression of neurological disorders was 3.5 (95% confidence interval (CI) 2.15–6.15), in the second — 25.0 (95% CI 24.14–29.58), in the third — 13.0 (95% CI 10.87–16.55). The differences are statistically significant (χ2 = 60.4, df = 2, p &lt; 0.0001). In patients with severe neurological disorders, the dynamics of recovery did not correlate with the pain intensity. With ASIA B, the dynamics of group 1 was 8.5 (95% CI 10.56–27.56), of group 2— 15.0 (95% CI 13.41–18.41), of group 3 — 10.5 (95% CI 7.45–14.89). With ASIA C functional class, the difference is even more pronounced: in group 1, the median was 8.0 (95% CI 0.83–20.83), in group 2 — 32.0 (95% CI 25.41–36.86), in group 3 — 15.5 (95% CI 10.27–27.4). With ASIA D, a similar trend was observed. Conclusions. The worst regression of neurological disorders is observed in patients without clinically significant pain, the best results of neurological dysfunction recovery are found in patients with mode rate neuropathic pain.

Effectiveness, Safety, and Tolerability of Nabiximols Oromucosal Spray vs Typical Oral Long-Acting Opioid Analgesics in Patients with Severe Neuropathic Back Pain: Analysis of 6-Month Real-World Data from the German Pain e-Registry.

ObjectiveTo compare the effectiveness, safety, and tolerability of add-on nabiximols (NBX) oromucosal spray vs typical oral long-acting opioid (LAO) analgesics in patients with severe (± chronic) peripheral neuropathic back pain poorly responsive to other treatments.MethodsRetrospective analysis of anonymized, propensity score–matched data from the German Pain e-Registry of adult outpatients who initiated NBX or LAO between March 2017 and March 2020.ResultsData were analyzed from propensity score–matched patients treated with NBX (n = 655) or LAO (n = 655): mean age ≈51 years; 57% female; mean pain duration ≈2.6 years; chronic pain 61%; severe dysfunctional pain 93%. At 6 months, NBX was noninferior to LAO for overall symptom relief, based on the least-squares mean difference between cohorts in change from baseline in patient-reported, pain-related aggregated nine-item scale scores (−27.84%; 95% confidence interval [CI] −29.71 to −25.96; P < 0.001) and individual pain-related scale scores. Subsequent prespecified superiority analysis of the primary endpoint showed that NBX was superior to LAO: all secondary endpoints measuring symptoms of pain and physical function improved significantly with NBX and LAO, with between-group differences favoring NBX (all P < 0.001). Fewer patients treated with NBX than LAO experienced treatment-related adverse events (25.5% vs 76.0%; P < 0.001) or discontinued treatment because of treatment-related adverse events (7.9% vs 29.3%; P < 0.001).ConclusionWithin study limitations (e.g., observational design, all potential biases), add-on NBX was superior to and better tolerated than add-on treatment with typical oral LAO analgesics in patients with neuropathic back pain inadequately controlled by recommended/established systemic therapies.

Alpha 1 adrenoceptor expression in skin, nerves and blood vessels of patients with painful diabetic neuropathy.

Diabetic neuropathy (dNP) patients often suffer from severe neuropathic pain. It was suggested that alpha-1 adrenoceptor (α1-AR) hyperresponsiveness contributes to pain in dNP. The aim of our study was to quantify α1-AR expression using immunohistochemistry in skin biopsies of nine patients with painful diabetic neuropathy compared to 10 healthy controls. Additionally, the association between α1-AR expression and activation with spontaneous and sympathetically maintained pain (SMP) induced by intradermal injection of the α1-agonist phenylephrine was investigated. For control purposes the α2-agonist clonidine was injected in a different session. We found that dermal nerve density was significantly lower in dNP than in controls. However, α1-AR expression was significantly greater on cutaneous blood vessels and keratinocytes of dNP patients than controls. A similar trend, which failed to reach significance, was observed for dermal nerves. Intradermal injection of phenylephrine induced only minor pain, which resolved after a few minutes. Adrenergically evoked pain persisted for more than 15min in only one patient, but none of the patients fulfilled the criteria for SMP (pain increase after injection of phenylephrine and decrease after clonidine). In conclusion, our results imply that SMP does not occur in dNP. However, elevated expression of α1-AR on keratinocytes and dermal blood vessels is an important finding, since this could contribute to dNP progression and supports the theory of receptor up-regulation of denervated structures. The implications of this α1-upregulation should be examined in further studies.

Hsa-MiR-19a-3p and hsa-MiR-19b-3p Are Associated with Spinal Cord Injury-Induced Neuropathic Pain: Findings from a Genome-Wide MicroRNA Expression Profiling Screen.

Neuropathic pain in spinal cord injury (SCI) is associated with inflammation in both the peripheral and central nervous system (CNS), which may contribute to the initiation and maintenance of persistent pain. An understanding of factors contributing to neuroinflammation may lead to new therapeutic targets for neuropathic pain. Moreover, novel circulating biomarkers of neuropathic pain may facilitate earlier and more effective treatment. MicroRNAs (miRNAs) are short, non-coding single-stranded RNA that have emerged as important biomarkers and molecular mediators in physiological and pathological conditions. Using a genome-wide miRNA screening approach, we studied differential miRNA expression in plasma from 68 healthy, community-dwelling adults with and without SCI enrolled in ongoing clinical studies. We detected 2367 distinct miRNAs. Of these, 383 miRNAs were differentially expressed in acute SCI or chronic SCI versus no SCI and 71 were differentially expressed in chronic neuropathic pain versus no neuropathic pain. We selected homo sapiens (hsa)-miR-19a-3p and hsa-miR-19b-3p for additional analysis based on p-value, fold change, and their known role as regulators of neuropathic pain and neuroinflammation. Both hsa-miR-19a-3p and hsa-miR-19b-3p levels were significantly higher in those with chronic SCI and severe neuropathic pain versus those with chronic SCI and no neuropathic pain. In confirmatory studies, both hsa-miR-19a-3p and hsa-miR-19b-3p have moderate to strong discriminative ability to distinguish between those with and without pain. After adjusting for opioid use, hsa-miR-19b-3p levels were positively associated with pain interference with mood. Because hsa-miR-19 levels have been shown to change in response to exercise, folic acid, and resveratrol, these studies suggest that miRNAs are potential targets of therapeutic interventions.

JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice.

Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of Aconitum carmichaelii, Angelica gigas, and Zingiber officinale. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 μg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.

Painful Diabetic Peripheral Neuropathy Study of Chinese Outpatients (PDNSCOPE): A Multicentre Cross-Sectional Registry Study of Clinical Characteristics and Treatment in Mainland China.

IntroductionThis aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices.MethodsA total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants’ demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded.ResultsThe male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350).ConclusionModerate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines.Trial registrationClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00281-w.

Short-Term Peripheral Nerve Stimulation Relieve Pain for Elder Herpes Zoster Ophthalmicus Patients: A Retrospective Study

ObjectiveOphthalmic postherpetic neuralgia (PHN) is the final stage of herpes zoster (HZ) ophthalmicus and a severe refractory neuropathic pain, thus there is no curative treatment that could alleviate pain and reduce the incidence of ophthalmic PHN now. The purpose of this study is to evaluate therapeutic efficacy of short‐term peripheral nerve stimulation (PNS) for elder patients with HZ ophthalmicus.Materials and MethodsWe performed a retrospective study from March 2015 to August 2019 in our pain department. All the HZ ophthalmicus patients underwent supraorbital nerve short‐term PNS were included. The patients' data, including numeric rating scale (NRS), 36‐Item short form health survey (SF‐36), and analgesic consumptions, were retrospectively analyzed. Severe side effects also were recorded.ResultsA total of 68 patients were enrolled in this study. The NRS scores were significantly decreased at different time points after short‐term PNS compared to baseline (p < 0.001). The SF‐36 scores, including general health, social function, emotional role, mental health, bodily pain, physical functioning, physical role, and vitality, were significantly improved at different time points after treatment (p < 0.001). The average dosages of tramadol and pregabalin administered (mg/d) were both significantly reduced compared to baseline (p < 0.001). There was no bleeding, infection, pain increase, and other side effects after treatment.ConclusionsShort‐term PNS is an effective and safe therapeutic alternative for elder patients with HZ ophthalmicus and could reduce the incidence of ophthalmic PHN.

Intraneural fibrosis and loss of microvascular architecture — Key findings investigating failed human nerve allografts

BackgroundProcessed nerve allografts are increasingly used in clinical nerve reconstruction with promising results. However, allograft failure has been reported, leading to chronic pain and persistent loss of function. In the present work, we performed a histological and immunohistochemical analysis of two failed allograft reconstructions of a sensory human nerve one year after primary surgery. MethodsTwo patients with a superficial radial nerve injury underwent nerve reconstruction with processed nerve allografts. The clinical follow-up was complicated by severe neuropathic pain and absent sensory reinnervation. Consequently, the failed allografts were excised with subsequent histological and immunohistochemical examinations. For that purpose, the collagen content and neurofilament network as well as the blood and lymphatic vasculature were analysed in the center of the specimens. ResultsHistology revealed increased fibrosis, fatty degeneration, and disorganised proliferation of nerve fibres. Moreover, the microvascular network within the allografts was characterised by increased numbers of microvessels, whereas no difference was found concerning the lymphatic vasculature. ConclusionThe herein presented histological and immunohistochemical findings indicate that the failure of human allografts is associated with loss of the physiological microvascular architecture. Future studies elucidating the complex interplay of angiogenesis, lymphangiogenesis and axonal regeneration are required to better understand the mechanisms of human allograft failure.

P-PN021. A case series of cryoglobulinemia with different clinical presentations and different nerve conduction studies (NCS) findings

Introduction . Neuropathy in cryoglobulinemia can be due to hyperviscosity (type I) or non obstructive immune complex mediated inflammatory vasculitis (type II and III). Methods . Case series: Our first patient was a 72-year-old gentleman with 5-month duration of severe asymmetrical neuropathic pain and rapidly progressive weakness in right peroneal and bilateral ulnar distribution associated with significant weight loss and pain, but no sphincter and autonomic dysfunction. He denied fever, arthritis, Raynaud’s phenomenon, rash and edema. His NCS revealed bilateral ulnar and right peroneal neuropathy. Left sural nerve biopsy revealed vasculitis, and cryoglobulin was found to be positive. Myeloma panel was suggestive of Kappa monoclonal gammopathy with normal flow cytometry and bone marrow. We concluded it as cryoglobulinemic vasculitis with Kappa light chain MGUS presenting with mononeuritis multiplex. Second patient was a 56-year-old man, HCV treated one year ago with undetectable viral load currently, and had generalized Myasthenia Gravis, presented with burning sensation of bilateral feet and erythematous macules, blanching papules on ankles, arms with normal power and reflexes. Nerve conduction study was normal and supported the clinical diagnosis of small fiber neuropathy due to cryoglobulinemia with treated HCV. Third case, a 70-year-old lady, presented with tingling sensation of both lower limbs with impaired sensation of up to ankles, distal toes weakness (3/5) and absent ankle reflexes for 2 months. Her NCS showed distal sensorimotor axonal polyneuropathy. She was found to be anti-HCV positive and cryoglobulinemia with viral load of 1 × 10 6 IU/ml. All our patients had no history of exposure to heavy metals, metabolic, infection screening and ENA, ANCA, anti-CCP were negative and cryoglobulin was positive. Conclusion . Nerve conduction study can add to the clinical for diagnosis of various types of polyneuropathy (mononeuritis multiplex, large fiber peripheral neuropathy, small fiber neuropathy) as depicted in our cases.

Role of Intravenous Lidocaine Infusion in the Treatment of Peripheral Neuropathy.

This is a comprehensive review of the literature regarding intravenous lidocaine infusion to treat peripheral neuropathy. The clinical symptoms of peripheral neuropathy occur on a broad spectrum and stem from many etiologies resulting in complex treatment approaches. This review presents the background, evidence, and indications for the use of intravenous lidocaine infusions as a treatment option for this condition. The clinical range of peripheral neuropathy symptoms includes pain, numbness, muscle weakness, paresthesia, balance difficulty, and autonomic dysfunction. However, severe neuropathic pain remains one of the most debilitating symptoms that significantly affects the quality of life. Current treatment options include antidepressants, anticonvulsants, and, in some cases, opiates, but these are often ineffective, creating the need for other therapeutic approaches.The pathophysiology of neuropathic pain involves sodium channels which create abnormal pain responses. Intravenous lidocaine primarily functions by inhibiting membrane sodium channels which desensitize peripheral nociceptors, thus creating an analgesic effect. The research in using intravenous lidocaine for neuropathic pain is not fully complete and requires further evaluation. Peripheral neuropathy is a manifestation commonly resulting from diabetes, alcohol abuse, vitamin deficiencies, and chemotherapy, among other causes. One of the most significant complications is neuropathic pain which is often resistant to multi-modal therapeutic regimens. Intravenous lidocaine infusions are a newer treatment option for neuropathic pain, which have additional anti-inflammatory effects with a minimal side effect profile. Studies have concluded it effectively treats neuropathic pain for weeks after administration, but results are variable depending on specific procedures. Further research, including additional direct comparison studies, should be conducted to fully evaluate this drug's usefulness.

Association between Trigeminal Neuralgia and Multiple Sclerosis: Role of Magnetic Resonance Imaging

Background: Trigeminal neuralgia (TN) is a severe neuropathic unilateral facial pain affecting about 30% percent of the world population. Neuropathic pains are considered to be associated with multiple sclerosis (MS).Multiple sclerosis is a chronic inflammatory condition causing demyelination and degeneration of axons in central nervous system. Objective: The objective of the study is to determine role of Magnetic Resonance Imaging to find association between trigeminal neuralgia and multiple sclerosis. Methods: The prospective cohort study was conducted for six months in Radiology Department of Hayatabad Medical Complex, Peshawar from September 2020 to February 2021. Initially 250 patients were screened for multiple sclerosis. The study recruited a total of 35 patients of MS visited neuroradiology department, out of which 26 patients were enrolled in the study. The participants with age of 18 years and onward of both genders with definitive symptoms of TN with MS that is having unilateral TN pain (that is sharp shooting electric pulse like) lasting for up-to 2minutes precipitated with an environmental stimulus were included in the study. The patients (n=6) with bilateral MS with TN and cognitive disturbances (n=3) were excluded from the study. Results: The study recruited a total of 26 participants with MS related TN. The clinical examination didn’t show any difference between the three groups with the p-value less than 0.001. Age at the onset of MS was younger in patients with MS related sensory disturbances compared to other two groups, with p-value less than 0.05. The frequency of the affected side was different in all three groups with the p-value less than 0.05 as tested by Fischer exact test. Trigeminal reflex tests done for different components such as R1 and SP1 showed longer latency periods for the affected side after stimulation and unaffected side after stimulation with the mean of 14.2± 4.4 and 15.3±3.2, 16.3±4.2 and 17.4±5.2ms and p-value less than 0.001 as shown by Wilcoxon test. Conclusion: The study showed significant association between trigeminal neuralgia and multiple sclerosis with the greater efficacy of using MRI as imaging technique to find this association. Keywords: Multiple sclerosis, Magnetic Resonance Imaging, Trigeminal neuralgia