Comparative effect of dense-and-disperse versus non-repetitive and non-sequential frequencies in electroacupuncture-induced analgesia in a rodent model of peripheral neuropathic pain

2021 ◽  
pp. 096452842110557
Author(s):  
Liaw Chao ◽  
Alexandre SR Gonçalves ◽  
Ana Carolina P Campos ◽  
Daniele V Assis ◽  
Rodrigo Jerônimo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Analgesic Effect ◽  
Complex Disease ◽  
Low Frequency ◽  
Acupuncture Point ◽  
Spontaneous Pain ◽  
Pain Scores ◽  
Additional Group ◽  
Male Wistar Rats ◽  
Random Frequency

Background: Neuropathic pain (NP) is a complex disease that remains challenging to treat. Low-frequency dense-and-disperse (DD) electroacupuncture (EA) has been used as adjuvant therapy for neuropathic pain; however, its analgesic effect decreases as stimulation time increases, or when it is repeatedly used. We hypothesized that a new frequency parameter could improve the effectiveness of EA, and aimed to compare the efficacy and duration of the analgesic effect between classic DD-EA and non-repetitive and non-sequential frequency (random frequency (RF)-EA) in neuropathic rats. Furthermore, the effect of RF-EA at local traditional acupuncture point locations versus auricular vagus nerve stimulation (aVNS) was evaluated. Methods: Male Wistar rats with peripheral neuropathy were subjected to a single session of DD-EA or RF-EA for 20 or 40 min at ST36 + GB34. An additional group of rats was treated with RF-EA for 20 min using aVNS at the appropriate ear point locations. Paw pressure test, von Frey filaments and spontaneous pain scores were evaluated. Sham-operated rats were used as controls. Results: In all, 20 min of RF-EA reversed hyperalgesia (for 24 h) and allodynia (for 8 h), showing a longer analgesic effect than DD-EA. Both RF-EA and DD-EA induced partial inhibition of spontaneous pain for 8 h. Forty minutes of DD-EA did not interfere with the NP phenomena; however, RF-EA induced significant long-term analgesia. aVNS induced an analgesic effect similar to local stimulation. Conclusion: This pilot study shows that RF-EA at both local traditional acupuncture point and auriculotherapy point locations induces long-lasting analgesia in neuropathic rats, and more effectively so than classical DD-EA.

scholarly journals Offset Analgesia in Neuropathic Pain Patients and Effect of Treatment with Morphine and Ketamine

2011 ◽  
Vol 115 (5) ◽  
pp. 1063-1071 ◽  
Author(s):  
Marieke Niesters ◽  
Elske Hoitsma ◽  
Elise Sarton ◽  
Leon Aarts ◽  
Albert Dahan
Keyword(s):  
Neuropathic Pain ◽  
Pain Score ◽  
Pain Perception ◽  
Spontaneous Pain ◽  
Noxious Heat ◽  
Convenience Sample ◽  
Pain Scores ◽  
Effect Of Treatment ◽  
Age Range ◽  
Pain Patients

Background Offset analgesia, in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation, has not been described previously in patients with chronic pain. Methods Offset analgesia responses in 10 patients with neuropathic pain (in both legs) were compared with 10 matched healthy controls and volunteers from a convenience sample (n = 110) with an age range of 6-80 yr. Offset analgesia was defined by the reduction in electronic pain score upon the 1°C decrease in noxious heat stimulus relative to the peak pain score where pain was administered at the volar side of the arm. Results Offset analgesia was present in healthy volunteers irrespective of age and sex (pain score decrease = 97 ± 1% [mean ± SEM]). In contrast, a reduced or absent offset analgesia response was observed in patients with neuropathic pain (pain score decrease = 56 ± 9% vs. controls 98 ± 1%, P < 0.001). Intravenous treatment with ketamine, morphine, and placebo had no effect on offset analgesia in patients, despite sharp reductions in spontaneous pain scores. Conclusions These data indicate that offset analgesia is fully developed at the age of 6 yr and does not undergo additional maturation. The reduced or absent responses observed in patients with chronic neuropathic pain indicate the inability to modulate changes in pain stimulation, with perseverance of pain perception in situations in which healthy subjects display signs of strong analgesia. Both central and peripheral sites may be involved in the altered offset analgesia responses in these patients.

Comparative analysis of labile and stable high-frequency TENS in the treatment of neuropathic pain syndrome

2021 ◽  
pp. 40-46
Author(s):  
M. Kh. Al-Zamil
Keyword(s):  
Neuropathic Pain ◽  
Comparative Analysis ◽  
High Frequency ◽  
Analgesic Effect ◽  
Low Frequency ◽  
Lower Extremities ◽  
Pain Syndrome ◽  
Neuropathic Pain Syndrome ◽  
Reduction Of Pain

Introduction: There have been many works devoted to the comparative analysis of high-frequency and low-frequency TENS in the treatment of neuropathic pain syndrome. Meanwhile, the comparative analysis of the methods of labile and stable TENS has not been sufficiently studied to date. Purpose: To make a comparative analysis of labile and stable high-frequency TENS in the treatment of neuropathic pain syndrome in patients with distal polyneuropathy of the lower extremities (DPLE). Materials and methods: 64 patients (F: 34, M: 30) with severe neuropathic pain syndrome on the background of diabetic DPLE were studied. Depending on the method of high-frequency TENS, all patients were divided into 2groups: stable high-frequency TENS (n=31) and labile high-frequency TENS (n=33). TENS was carried out every other day for a month. The severity of pain was determined by the VAS before each procedure. Results: The reduction of pain syndrome with the use of labile stimulation was 76.9%, compared to stable stimulation — 41,6%. With daily registration of pain syndrome, a significant increase in pain syndrome was revealed in patients who underwent stable high-frequency TENS after the 7th procedure to 4,5±0,3points in comparison with the indicators of pain syndrome obtained after the 3rd procedure (3,2±0,14). Conclusions: The analgesic effect of the labile high-frequency TENS significantly exceeds the analgesic effect of the stable high-frequency TENS by 85.1%. Partial tolerance to high-frequency TENS is observed when applying stable stimulation, which develops after the 7th procedure and is not observed after labile TENS.

Concentration–Effect Relationship of Intravenous Lidocaine on the Allodynia of Complex Regional Pain Syndrome Types I and II

2000 ◽  
Vol 92 (1) ◽  
pp. 75-75 ◽  
Author(s):  
Mark S. Wallace ◽  
Beri M. Ridgeway ◽  
Albert Y. Leung ◽  
Afshin Gerayli ◽  
Tony L. Yaksh
Keyword(s):  
Neuropathic Pain ◽  
Plasma Level ◽  
Plasma Levels ◽  
Pain Syndrome ◽  
Spontaneous Pain ◽  
Intravenous Lidocaine ◽  
Pain Thresholds ◽  
Pain Scores ◽  
Painful Area ◽  
Neurosensory Testing

Background Several lines of evidence suggest that neuropathic pain (including Complex Regional Pain Syndrome [CRPS] I and CRPS II) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. This study sought to characterize the effects of intravenous lidocaine (a sodium channel blocker) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II. Methods This study used a randomized, double-blind, placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia. Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week. A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1, 2, and 3 microg/ml. At baseline and at each plasma level, spontaneous and evoked pain scores and neurosensory testing within the painful area were measured. The neurosensory testing consisted of thermal thresholds, tactile thresholds and the area of allodynia to punctate, and stroking and thermal stimuli. Results Intravenous lidocaine and diphenhydramine had no significant effect on the cool, warm, or cold pain thresholds. However, lidocaine caused a significant elevation of the hot pain thresholds in the painful area. Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area. There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level. Conclusions This study demonstrates that intravenous lidocaine affects pain in response to cool stimuli more than mechanical pain in subjects with neuropathic pain. There is a lesser effect on spontaneous pain and pain induced by stroking stimuli and no effect on the pain induced by punctate stimuli.

Effect of Transcutaneous Electrical Acupuncture Point Stimulation at Different Frequencies in a Rat Model of Neuropathic Pain

2017 ◽  
Vol 35 (2) ◽  
pp. 142-147 ◽  
Author(s):  
Xiangdi Yu ◽  
Fangxiang Zhang ◽  
Bingning Chen
Keyword(s):  
Neuropathic Pain ◽  
Rat Model ◽  
High Frequency ◽  
Low Frequency ◽  
Acupuncture Point ◽  
Control Group ◽  
High Frequency Stimulation ◽  
Sprague Dawley ◽  
Electrical Acupuncture ◽  
Frequency Stimulation

Background Acupuncture and related techniques are used worldwide to alleviate pain; however, their mechanisms of action are still not fully understood. In the present study, we investigated the effect of transcutaneous electrical acupuncture point stimulation (TEAS) at different frequencies in a chronic constriction injury (CCI) model of neuropathic pain in rats. Methods CCI was induced by ligating the common sciatic nerve, which produced neuropathic pain. 18 male Sprague–Dawley rats with CCI were randomly divided into three groups (n=6 each) that remained untreated (CCI group) or received TEAS at high frequency (CCI+TEAS-H group) or TEAS at low frequency (CCI+TEAS-L group). Rats in the CCI+TEAS-H group received high frequency stimulation (6–9 mA, 100 Hz) at GB34/GV26/ST36; those in the CCI+TEAS-L group received low frequency stimulation (6–9 mA, 2 Hz) at the same points. Rats in the control group had the same electrodes applied but received no stimulation. All three groups were subjected to behavioural studies after treatment. Expression of μ opioid receptors (MORs) in the L3–L5 dorsal root ganglion (DRG) was determined by immunofluorescence staining and Western blotting after treatment. Results Compared with the untreated CCI group, both mechanical allodynia and thermal hypergesia were significantly attenuated, and MOR expression in the DRG was significantly increased by low frequency TEAS treatment at GB34/GV26/ST36 (p<0.05). In contrast, no significant differences were observed between the CCI and CCI+TEAS-H groups. Conclusions The use of low frequency TEAS significantly mitigated neuropathic pain in this rat model, and its analgesic effect is likely mediated by upregulation of MOR expression in the DRG.

scholarly journals Differential effects of epidermal growth factor receptor inhibitors in a single patient with neuropathic pain

2021 ◽  
Vol 14 (3) ◽  
pp. e239385
Author(s):  
Marte Grønlie Cameron ◽  
Christian Kersten
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Neuropathic Pain ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Differential Effects ◽  
Pain Scores ◽  
Medical Need ◽  
Epidermal Growth ◽  
Egfr Family

Neuropathic pain (NP) represents an unmet medical need, where analgesic responses to different epidermal growth factor receptor inhibitors (EGFR-Is) have been described. The human EGFR family of receptors consists of four members (human epidermal growth factor receptor, HER 1–4), signalling via different homodimer and heterodimer combinations. A 52-year-old man was treated with the EGFR-I cetuximab in a trial of severe NP. Pain scores decreased dramatically after blinded cetuximab, but not after placebo. On pain recurrence after the trial, he was prescribed the oral EGFR-Is erlotinib, gefitinib, and lapatinib without relief. However, treatment with the pan-HER-inhibitor afatinib was effective. After 4 years on afatinib, pain control remains excellent with manageable side effects. This is the first reported observation of differential effects of EGFR-Is on NP in the same patient and the first report describing NP relief with afatinib. Further understanding of the underlying pathophysiology could lead to development of EGFR-Is specifically targeting NP.

scholarly journals A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Evangelina López de Maturana ◽  
◽  
Juan Antonio Rodríguez ◽  
Lola Alonso ◽  
Oscar Lao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Functional Analysis ◽  
Genetic Susceptibility ◽  
In Silico ◽  
Complex Disease ◽  
Meta Analysis ◽  
Low Frequency ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Phenotypic Variance

Abstract Background Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. Methods We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants. Results We identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E−06 in 1D approach and a Local Moran’s Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8—a lncRNA associated with pancreatic carcinogenesis—with a lowest p value = 6.91E−05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1—a major regulator of the ER stress and unfolded protein responses in acinar cells—identified by 3D; all of them with a strong in silico functional support. Conclusions This multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases.

Pain Syndrome, Markers of Bone Metabolism in Patients with Osteoarthritis, Approaches to Drug Therapy and the Impact of Obesity

2016 ◽  
pp. 26-35
Author(s):  
Oleksandr Kuryata ◽  
Anna Cherkasova
Keyword(s):  
Neuropathic Pain ◽  
Bone Metabolism ◽  
Clinical Efficacy ◽  
Functional Ability ◽  
Analgesic Effect ◽  
Pain Syndrome ◽  
Knee Joints ◽  
Osteocalcin Level ◽  
Positive Effects ◽  
The Impact

The objective: to assess the nature of pain in patients with osteoarthritis, the impact of obesity on the clinical efficacy of treatment of osteoarthritis (OA) and dynamics of bone metabolism markers. Patients and methods. The research included 150 patients with OA, who were divided into two groups, according to the receiving therapy. Patients of the main group – received diacerein (drug «Flexirin» PC «Kyiv Vitamin Factory») and patients of control group – received only nonsteroidal anti1inflammatory drugs (NSAIDs). Results. The prevalence of neuropathic pain component in patients with OA was 64,7%, among which 80,7% use NSAIDs as an analgesic therapy. Obesity in patients with OA was associated with significantly higher levels of pain from the side of knee joints and higher degree of stiffness according to WOMAC index. The results of the study demonstrated a direct moderate correlation (R = 0,49; p = 0,04) between PICP level and the severity of pain at physical load from the side of hands and hip joints. The therapy by diacerein within 3 months resulted in a reliable decrease of pain syndrome intensity from the side of all articular zones, unlike to isolated NSAIDs use, where a reliable analgesic effect was demonstrated only from the side of knee joints. Obesity in patients with OA led to a significant decrease in clinical efficacy of therapy in point of functional status of the joints. Conclusions. Neuropathic pain is quite common among patients with OA, which at the same time is associated with the lack of patient’s awareness about possible risks during NSAID’s use. Medical treatment by diacerein (drug “Flexirin”) causes stability of osteocalcin level, in contrast to the isolated NSAIDs use, where priority changes have been demonstrated against osteocalcin level decrease. The use of diacerein also resulted to additional positive effects from the side of zonal prevalence of analgesic effect and improving of functional ability of joints. Obesity in patients with OA was associated with a reliable increase of pain level intensity from the side of knee joints and the higher degree of functional limitation, causing at the same time, reduction of clinical efficacy of therapy in point of achieving analgesic effect and improving functional ability of joints.

scholarly journals Central Neuropathic Pain in a Patient with Multiple Sclerosis Treated Successfully with Topical Amitriptyline

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
David J. Kopsky ◽  
Remko Liebregts ◽  
Jan M. Keppel Hesselink
Keyword(s):  
Multiple Sclerosis ◽  
Neuropathic Pain ◽  
Adverse Events ◽  
Active Compound ◽  
Analgesic Effect ◽  
Tricyclic Antidepressants ◽  
Double Blind ◽  
Carryover Effect ◽  
Double Blind Placebo ◽  
Central Neuropathic Pain

Central neuropathic pain in patients with multiple sclerosis (MS) is a common debilitating symptom, which is mostly treated with tricyclic antidepressants or antiepileptics. Unfortunately, the use of these drugs is often limited due to adverse events. We investigated the analgesic effect of topical amitriptyline 5% and 10% cream in a patient with central neuropathic pain due to MS. The analgesic effect of topical amitriptyline cream on neuropathic pain was dose related. To evaluate whether this analgesic effect is due to the active compound or placebo, we conducted a double-blind placebo-controlled n-of-1 study with amitriptyline 5% cream and placebo. The instruction was to alternate the creams every week following the pattern ABAB, with an escape possibility of amitriptyline 10% cream. The result was a complete pain reduction after application of cream B, while most of the time cream A did not reduce the pain. The patient could correctly unblind both creams, determining B as active. She noted that in the week of using the active cream no allodynia was present, with a carryover effect of one day.

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