scholarly journals Mirogabalin—A Novel Selective Ligand for the α2δ Calcium Channel Subunit

2021 ◽  
Vol 14 (2) ◽  
pp. 112
Author(s):  
Renata Zajączkowska ◽  
Joanna Mika ◽  
Wojciech Leppert ◽  
Magdalena Kocot-Kępska ◽  
Małgorzata Malec-Milewska ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Significant Proportion ◽  
Safety Margin ◽  
Dissociation Rate ◽  
New Drugs ◽  
Peripheral Neuropathic Pain ◽  
Ligand Selectivity ◽  
Analgesic Effects ◽  
Pain Syndromes ◽  
Selective Ligand

The efficacy of neuropathic pain control remains unsatisfactory. Despite the availability of a variety of therapies, a significant proportion of patients suffer from poorly controlled pain of this kind. Consequently, new drugs and treatments are still being sought to remedy the situation. One such new drug is mirogabalin, a selective ligand for the α2δ subunits of voltage-gated calcium channels (VGCC) developed by Sankyo group for the management of neuropathic pain. In 2019 in Japan, mirogabalin was approved for peripheral neuropathic pain following the encouraging results of clinical trials conducted with diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) patients. The ligand selectivity of mirogabalin for α2δ-1 and α2δ-2 and its slower dissociation rate for α2δ-1 than for α2δ-2 subunits of VGCC may contribute to its strong analgesic effects, wide safety margin, and relatively lower incidence of adverse effects compared to pregabalin and gabapentin. This article discusses the mechanism of action of mirogabalin, presents data on its pharmacodynamics and pharmacokinetics, and reviews the available experimental and clinical studies that have assessed the efficacy and safety of the drug in the treatment of selected neuropathic pain syndromes.

scholarly journals Mirogabalin as a Novel Gabapentinoid for the Treatment of Chronic Pain Conditions: An Analysis of Current Evidence

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Eric Y. Chen ◽  
Sascha S. Beutler ◽  
Alan D. Kaye ◽  
Amber N. Edinoff ◽  
Seyed-Hossein Khademi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Neurotransmitter Release ◽  
Safety Margin ◽  
Current Evidence ◽  
Multimodal Approach ◽  
Peripheral Neuropathic Pain ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Selective Ligand ◽  
Chronic Pain Conditions

: Neuropathic pain has presented a challenge for physicians to treat and often requires a multimodal approach with both pharmacologic and lifestyle interventions. Mirogabalin, a potent, selective ligand of the α2δ-1 and α2δ-2 subunits of voltage-gated calcium channels (VGCCs), provides analgesia by inhibiting neurotransmitter release at the presynaptic end of the neuron. Mirogabalin offers more sustained analgesia than its gabapentinoid counterparts in addition to a wider safety margin for adverse events. Recent clinical trials of mirogabalin have demonstrated both efficacy and tolerability of the drug for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia, leading to its approval in Japan. While still not yet FDA approved, mirogabalin is still in its infancy and offers potential into the treatment of neuropathic pain and its associated comorbidities.

On the pharmacological effects of two lidocaine concentrations tested on spontaneous and evoked pain in human painful neuroma: A new clinical model of neuropathic pain

2013 ◽  
Vol 4 (4) ◽  
pp. 258
Author(s):  
Adriana Miclescu ◽  
Björn Hägglöf ◽  
Martin Schmelz ◽  
Torsten Gordh
Keyword(s):  
Neuropathic Pain ◽  
Clinical Symptoms ◽  
Control Level ◽  
New Drugs ◽  
Spontaneous Pain ◽  
Double Blind ◽  
Clinical Model ◽  
Analgesic Effects ◽  
Proposed Model ◽  
Before And After

AbstractAimsSpontaneous and evoked pains are key symptoms of patients with neuropathic pain and there is a current discussion on the predictive value of evoked pain read outs for the reduction of spontaneous pain. Here we describe a new clinical model of neuropathic pain that may be useful for evaluation of new drugs. We also report the effects of lidocaine in this model as reference values.MethodsIn a randomized double-blind experiment, the analgesic effects of local lidocaine were investigated separately for spontaneous pain and for stimulus-evoked allodynia and hyperalgesia in sixteen patients with painful neuromas after traumatic nerve injuries in the upper extremities. The patterns of sensory changes were compared before and after treatment with lidocaine (0.1% or 0.5%, 1 ml), with 1–2 weeks interval, injected close to the neuroma. Spontaneous and evoked pains were assessed using a visual analogue scale (VAS) and quantitative/qualitative sensory testing.ResultsLidocaine dose-dependently reduced spontaneous and evoked pain scores by more than 90% with maximum effects between 1 and 5 min for evoked pain and between 3 and 15 min for spontaneous pain. While evoked pain normalized rapidly reaching about 50% of the control level 20 minutes after the injection spontaneous pain levels were lower than 25% at this time. Moreover, in 4 patients the reduction of ongoing pain lasted 24 h whereas evoked pain had returned to baseline levels in all the patients after 1 h.ConclusionDifferential analgesic effects of local lidocaine on spontaneous and evoked pain suggest that different mechanism underlie these two key clinical symptoms. Thus, clinical trials assessing localized traumatic neuropathic pain should investigate both aspects of pain separately with the proposed model allowing testing of new drugs systemically or locally administered.

scholarly journals Effects of alkaloids on peripheral neuropathic pain: a review

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Chunhao Zhu ◽  
Ning Liu ◽  
Miaomiao Tian ◽  
Lin Ma ◽  
Jiamei Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Molecular Mechanisms ◽  
Herbal Medicines ◽  
New Drugs ◽  
Intractable Pain ◽  
Chinese Herbal Medicines ◽  
Peripheral Neuropathic Pain ◽  
Chinese Herbal ◽  
Toxicological Studies ◽  
Novel Drugs

Abstract Neuropathic pain is a debilitating pathological pain condition with a great therapeutic challenge in clinical practice. Currently used analgesics produce deleterious side effects. Therefore, it is necessary to investigate alternative medicines for neuropathic pain. Chinese herbal medicines have been widely used in treating intractable pain. Compelling evidence revealed that the bioactive alkaloids of Chinese herbal medicines stand out in developing novel drugs for neuropathic pain due to multiple targets and satisfactory efficacy. In this review, we summarize the recent progress in the research of analgesic effects of 20 alkaloids components for peripheral neuropathic pain and highlight the potential underlying molecular mechanisms. We also point out the opportunities and challenges of the current studies and shed light on further in-depth pharmacological and toxicological studies of these bioactive alkaloids. In conclusion, the alkaloids hold broad prospects and have the potentials to be novel drugs for treating neuropathic pain. This review provides a theoretical basis for further applying some alkaloids in clinical trials and developing new drugs of neuropathic pain.

scholarly journals Posttranslational Sodium ion Channel Modifications and the use of Topical Phenytoin in Painful Diabetic Neuropathy (PDN)

2018 ◽  
Vol 3 (1) ◽  
Keyword(s):  
Neuropathic Pain ◽  
Diabetic Neuropathy ◽  
Channel Blocker ◽  
Sodium Ion ◽  
Painful Diabetic Neuropathy ◽  
Sodium Channel Blocker ◽  
Onset Of Action ◽  
Peripheral Neuropathic Pain ◽  
Pain Syndromes ◽  
Number Of Patients

Phenytoin is a broad acting sodium channel blocker we deem fit for topical formulations to treat localized peripheral neuropathic pain. We tested this cream in a number of patients suffering from neuropathic pain syndromes and found it to be especially of use in small fiber neuropathic pain and in painful diabetic neuropathy. The fact that patients report an onset of action within 30 minutes, and the absence of detectable plasma levels of phenytoin, support an intra-epidermal mechanism of action. In this paper, we launch a hypothesis why phenytoin might be of particular use in peripheral neuropathic pain syndromes such as painful diabetic neuropathy

Clinical Efficacy of Aconitum-Containing Traditional Chinese Medicine for Diabetic Peripheral Neuropathic Pain

2014 ◽  
Vol 42 (01) ◽  
pp. 109-117 ◽  
Author(s):  
Ling Feng ◽  
Wen-Ke Liu ◽  
Lan Deng ◽  
Jia-Xing Tian ◽  
Xiao-Lin Tong
Keyword(s):  
Neuropathic Pain ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Adverse Reactions ◽  
Nerve Repair ◽  
Well Being ◽  
High Dose ◽  
Peripheral Neuropathic Pain ◽  
Analgesic Effects ◽  
Relieve Pain

Diabetic peripheral neuropathy is a common chronic complication of diabetes. Routine clinical management uses analgesics to relieve pain in combination with drugs for nerve repair. The drugs are often not effective for the severe pain cases, and these western medications also have side effects. We report a more effective treatment of diabetic peripheral neuropathic pain using a high dose of a traditional Chinese medicine, aconitum (including both Radix aconite preparata and Radix aconite kusnezoffii), in combination with Huangqi Guizhi Wuwu Tang (i.e., astragalus, cassia twig, white peony root, and spatholobi). In order to achieve stronger analgesic effects, we increased the clinical dosage of aconitum from 15 to 120 g. The aconitum was boiled for 6–8 hours, and licorice was also used to reduce potential toxicities of aconitum. In the four reported cases, the patients' neuropathic pain was remarkably reduced and the EMG profile was also improved with this treatment regimen. Adverse reactions were not observed during the therapy. Thus, aconitum represents a promising and safe treatment for the well-being of patients and their diabetic peripheral neuropathic pain. Future controlled clinical trials using traditional Chinese medicines containing aconitum in treating the neuropathic pain are warranted.

scholarly journals A.02 Long-term outcomes in the management of central neuropathic pain syndromes

2018 ◽  
Vol 45 (s2) ◽  
pp. S9-S9
Author(s):  
MD Staudt ◽  
AJ Clark ◽  
AS Gordon ◽  
ME Lynch ◽  
PK Morley-Forster ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Primary Outcome ◽  
Pain Interference ◽  
Peripheral Neuropathic Pain ◽  
Central Neuropathic Pain ◽  
Pain Syndromes ◽  
Cord Injury ◽  
Patient Reported

Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, spinal cord injury, or multiple sclerosis. These syndromes are much less common than peripheral etiologies, with less known regarding optimal treatment. The objective of this study was to determine the long-term clinical effectiveness of the management of central relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified from a prospective observational cohort from seven Canadian tertiary centers. Data regarding patient -characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome was the composite of reduced average pain intensity and pain interference. Secondary outcomes included assessments of function, mood, and quality-of-life. Results: At 12-month follow-up, 13.5% (95%CI,5.6-25.8) of patients achieved ≥30% reduction in pain, whereas 38.5% (95%CI,25.3-53.0) achieved a ≥1 point reduction in pain interference; 9.6% (95%CI,3.2-21.0) of patients achieving both these measures. Patients with peripheral neuropathic pain were more likely to achieve this primary outcome at 12-months (25.3% of patients; 95%CI,21.4-29.5) (p=.012). Conclusions: Patients with central neuropathic pain were less likely to achieve a meaningful improvement in pain and function compared to patients with peripheral neuropathic pain at 12-month follow-up.

Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study

Pain ◽  
2003 ◽  
Vol 106 (1) ◽  
pp. 151-158 ◽  
Author(s):  
Torsten Meier ◽  
Gunnar Wasner ◽  
Markus Faust ◽  
Thierry Kuntzer ◽  
François Ochsner ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Controlled Study ◽  
Double Blind ◽  
Peripheral Neuropathic Pain ◽  
Double Blind Placebo ◽  
Pain Syndromes ◽  
Lidocaine Patch

scholarly journals Long-Term Outcomes in the Management of Central Neuropathic Pain Syndromes: A Prospective Observational Cohort Study

2018 ◽  
Vol 45 (5) ◽  
pp. 545-552 ◽  
Author(s):  
Michael D. Staudt ◽  
Alexander John Clark ◽  
Allan S. Gordon ◽  
Mary E. Lynch ◽  
Pat K. Morley-Forster ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Primary Outcome ◽  
Data Sets ◽  
Long Term Outcomes ◽  
Peripheral Neuropathic Pain ◽  
Central Neuropathic Pain ◽  
Pain Syndromes ◽  
Observational Cohort

AbstractBackground:Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers.Methods:Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction.Results:At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012).Conclusion:Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.

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