scholarly journals Peripheral Mechanisms of Neuropathic Pain—The Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain

2021 ◽  
Vol 14 (2) ◽  
pp. 77
Author(s):  
Magdalena Kocot-Kępska ◽  
Renata Zajączkowska ◽  
Joanna Mika ◽  
Jerzy Wordliczek ◽  
Jan Dobrogowski ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Structural Changes ◽  
Neuronal Cells ◽  
Special Focus ◽  
Peripheral Sensitization ◽  
Peripheral Neuropathic Pain ◽  
Topical Analgesics ◽  
Underlying Mechanisms

Neuropathic pain in humans arises as a consequence of injury or disease of somatosensory nervous system at peripheral or central level. Peripheral neuropathic pain is more common than central neuropathic pain, and is supposed to result from peripheral mechanisms, following nerve injury. The animal models of neuropathic pain show extensive functional and structural changes occurring in neuronal and non-neuronal cells in response to peripheral nerve injury. These pathological changes following damage lead to peripheral sensitization development, and subsequently to central sensitization initiation with spinal and supraspinal mechanism involved. The aim of this narrative review paper is to discuss the mechanisms engaged in peripheral neuropathic pain generation and maintenance, with special focus on the role of glial, immune, and epithelial cells in peripheral nociception. Based on the preclinical and clinical studies, interactions between neuronal and non-neuronal cells have been described, pointing out at the molecular/cellular underlying mechanisms of neuropathic pain, which might be potentially targeted by topical treatments in clinical practice. The modulation of the complex neuro-immuno-cutaneous interactions in the periphery represents a strategy for the development of new topical analgesics and their utilization in clinical settings.

scholarly journals Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain—Narrative Review

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 450
Author(s):  
Magdalena Kocot-Kępska ◽  
Renata Zajączkowska ◽  
Joanna Mika ◽  
David J. Kopsky ◽  
Jerzy Wordliczek ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Pain Management ◽  
Clinical Studies ◽  
Neuronal Cells ◽  
Case Series ◽  
Narrative Review ◽  
Peripheral Sensitization ◽  
Cellular Mechanisms ◽  
Peripheral Neuropathic Pain ◽  
Topical Treatments

Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in pain management methods made to date, peripheral neuropathic pain significantly impacts patients’ quality of life, as pharmacological and non-pharmacological methods often fail or induce side effects. Topical treatments are gaining popularity in the management of peripheral neuropathic pain, due to excellent safety profiles and preferences. Moreover, topical treatments applied locally may target the underlying mechanisms of peripheral sensitization and pain. Recent studies showed that peripheral sensitization results from interactions between neuronal and non-neuronal cells, with numerous signaling molecules and molecular/cellular targets involved. This narrative review discusses the molecular/cellular mechanisms of drugs available in topical formulations utilized in clinical practice and their effectiveness in clinical studies in patients with peripheral neuropathic pain. We searched PubMed for papers published from 1 January 1995 to 30 November 2020. The key search phrases for identifying potentially relevant articles were “topical AND pain”, “topical AND neuropathic”, “topical AND treatment”, “topical AND mechanism”, “peripheral neuropathic”, and “mechanism”. The result of our search was 23 randomized controlled trials (RCT), 9 open-label studies, 16 retrospective studies, 20 case (series) reports, 8 systematic reviews, 66 narrative reviews, and 140 experimental studies. The data from preclinical studies revealed that active compounds of topical treatments exert multiple mechanisms of action, directly or indirectly modulating ion channels, receptors, proteins, and enzymes expressed by neuronal and non-neuronal cells, and thus contributing to antinociception. However, which mechanisms and the extent to which the mechanisms contribute to pain relief observed in humans remain unclear. The evidence from RCTs and reviews supports 5% lidocaine patches, 8% capsaicin patches, and botulinum toxin A injections as effective treatments in patients with peripheral neuropathic pain. In turn, single RCTs support evidence of doxepin, funapide, diclofenac, baclofen, clonidine, loperamide, and cannabidiol in neuropathic pain states. Topical administration of phenytoin, ambroxol, and prazosin is supported by observational clinical studies. For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series. For topical ketamine and baclofen, data supporting their effectiveness are provided by both single RCTs and case series. The discussed data from clinical studies and observations support the usefulness of topical treatments in neuropathic pain management. This review may help clinicians in making decisions regarding whether and which topical treatment may be a beneficial option, particularly in frail patients not tolerating systemic pharmacotherapy.

Neuropathic pain models in the development of analgesic drugs

2011 ◽  
Vol 2 (4) ◽  
pp. 172-177 ◽  
Author(s):  
Per Hartvig Honoré ◽  
Anna Basnet ◽  
Laila Eljaja ◽  
Pernille Kristensen ◽  
Lene Munkholm Andersen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Nerve Injury ◽  
Clinical Manifestations ◽  
Pharmacological Intervention ◽  
Special Focus ◽  
Surgical Performance ◽  
Neuropathic Pain Syndrome ◽  
Pain Models ◽  
Rats And Mice

AbstractIntroductionAnimal disease models are predictive for signs seen in disease. They may rarely mimic all signs in a specific disease in humans with respect to etiology, cause or development. Several models have been developed for different pain states and the alteration of behavior has been interpreted as a response to external stimulus or expression of pain or discomfort. Considerable attention must be paid not to interpret other effects such as somnolence or motor impairment as a pain response and similarly not to misinterpret the response of analgesics.Neuropathic pain is caused by injury or disease of the somatosensory system. The clinical manifestations of neuropathic pain vary including both stimulus-evoked and non-stimulus evoked (spontaneous) symptoms. By pharmacological intervention, the threshold for allodynia and hyperalgesia in the various pain modalities can be modulated and measured in animals and humans. Animal models have been found most valuable in studies on neuropathic pain and its treatment.Aim of the studyWith these interpretation problems in mind, the present text aims to describe the most frequently used animal models of neuropathic pain induced by mechanical nerve injury.MethodsThe technical surgical performance of these models is described as well as pain behavior based on the authors own experience and from a literature survey.ResultsNerve injury in the hind limb of rats and mice is frequently used in neuropathic pain models and the different types of lesion may afford difference in the spread and quality of the pain provoked. The most frequently used models are presented, with special focus on the spared nerve injury (SNI) and the spinal nerve ligation/transection (SNL/SNT) models, which are extensively used and validated in rats and mice. Measures of mechanical and thermal hypersensitivity with von Frey filaments and Hargreaves test, respectively, are described and shown in figures.ConclusionsA number of animal models have been developed and described for neuropathic pain showing predictive value in parallel for both humans and animals. On the other hand, there are still large knowledge gaps in the pathophysiologic mechanisms for the development, maintenance and progression of the neuropathic pain syndromeImplicationsBetter understanding of pathogenic mechanisms of neuropathic pain in animal models may support the search for new treatment paradigms in patients with complex neuropathic pain conditions

The Role of Nitric Oxide Synthase Isoforms in Neuropathic Pain Induced by Nerve Injury in Rats

2005 ◽  
Vol 48 (1) ◽  
pp. 76
Author(s):  
Young Tae Jeon ◽  
Kwang Suk Seo ◽  
Young Jin Ro ◽  
Young Jin Lim ◽  
Seong Won Min ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Neuropathic Pain ◽  
Nitric Oxide Synthase ◽  
Nerve Injury ◽  
Oxide Synthase

Antidepressants in Cancer Pain

1991 ◽  
Vol 7 (4) ◽  
pp. 42-44 ◽  
Author(s):  
Alberto E. Panerai ◽  
Mauro Bianchi ◽  
Paola Sacerdote ◽  
Carla Ripamonti ◽  
Vittorio Ventafridda ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cancer Pain ◽  
Beneficial Effect ◽  
Nerve Injury ◽  
Analgesic Effect ◽  
Tricyclic Antidepressants ◽  
Antidepressant Drugs ◽  
Depressive Illness ◽  
Morphine Analgesia

Studies conducted in recent years have helped define the role of antidepressant drugs in the management of cancer pain. The anti-nociceptive action of these agents seems to be independent of beneficial effect on depression or mood. Among antidepressant drugs, those of the tricyclic class are preferred when an analgesic effect is sought. Their primary application is for pain due to nerve injury, so-called “neuropathic pain”. Although the co-administration of tricyclic antidepressants may increase plasma morphine concentrations, any potentiation of morphine analgesia is thought not to be due to an increased bioavailability of the opiate, but to an intrinsic analgesic effect of antidepressants. On this basis, the use of antidepressants in combination with opioids for the treatment of cancer pain is suitable when a component of deafferentation is present or when there is concomitant depressive illness.

scholarly journals ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain

2020 ◽  
Vol 21 (15) ◽  
pp. 5330 ◽  
Author(s):  
Ramona D’Amico ◽  
Daniela Impellizzeri ◽  
Salvatore Cuzzocrea ◽  
Rosanna Di Paola
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Mast Cells ◽  
Inflammatory Responses ◽  
Bioactive Lipids ◽  
Peripheral Neuropathic Pain ◽  
Novel Approach ◽  
Preclinical And Clinical Studies ◽  
Somatosensory Nervous System

Neuropathic pain results from lesions or diseases of the somatosensory nervous system and it remains largely difficult to treat. Peripheral neuropathic pain originates from injury to the peripheral nervous system (PNS) and manifests as a series of symptoms and complications, including allodynia and hyperalgesia. The aim of this review is to discuss a novel approach on neuropathic pain management, which is based on the knowledge of processes that underlie the development of peripheral neuropathic pain; in particular highlights the role of glia and mast cells in pain and neuroinflammation. ALIAmides (autacoid local injury antagonist amides) represent a group of endogenous bioactive lipids, including palmitoylethanolamide (PEA), which play a central role in numerous biological processes, including pain, inflammation, and lipid metabolism. These compounds are emerging thanks to their anti-inflammatory and anti-hyperalgesic effects, due to the down-regulation of activation of mast cells. Collectively, preclinical and clinical studies support the idea that ALIAmides merit further consideration as therapeutic approach for controlling inflammatory responses, pain, and related peripheral neuropathic pain.

scholarly journals In Vitro and In Vivo Effects of Flavonoids on Peripheral Neuropathic Pain

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1171 ◽  
Author(s):  
Paramita Basu ◽  
Arpita Basu
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Nerve Injury ◽  
Somatosensory System ◽  
Present Review ◽  
Common Symptom ◽  
Murine Models ◽  
Peripheral Neuropathic Pain

Neuropathic pain is a common symptom and is associated with an impaired quality of life. It is caused by the lesion or disease of the somatosensory system. Neuropathic pain syndromes can be subdivided into two categories: central and peripheral neuropathic pain. The present review highlights the peripheral neuropathic models, including spared nerve injury, spinal nerve ligation, partial sciatic nerve injury, diabetes-induced neuropathy, chemotherapy-induced neuropathy, chronic constriction injury, and related conditions. The drugs which are currently used to attenuate peripheral neuropathy, such as antidepressants, anticonvulsants, baclofen, and clonidine, are associated with adverse side effects. These negative side effects necessitate the investigation of alternative therapeutics for treating neuropathic pain conditions. Flavonoids have been reported to alleviate neuropathic pain in murine models. The present review elucidates that several flavonoids attenuate different peripheral neuropathic pain conditions at behavioral, electrophysiological, biochemical and molecular biological levels in different murine models. Therefore, the flavonoids hold future promise and can be effectively used in treating or mitigating peripheral neuropathic conditions. Thus, future studies should focus on the structure-activity relationships among different categories of flavonoids and develop therapeutic products that enhance their antineuropathic effects.

scholarly journals The high-affinity IgG receptor FcγRI modulates peripheral nerve injury-induced neuropathic pain in rats

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingxia Liang ◽  
Zhiyu Zhang ◽  
Zhaodong Juan ◽  
Rui Zhang ◽  
Can Zhang
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Cell Model ◽  
Thermal Hyperalgesia ◽  
High Affinity ◽  
Gamma Receptor ◽  
High Affinity Receptor ◽  
Underlying Mechanisms

Abstract The Fc gamma receptor I (FcγRI; CD64) is the high-affinity receptor of the immunoglobulin G protein (IgG). It is usually expressed in immune cells and has recently been identified to distribute in the nervous system and play critical roles in various neurological disorders. Presently, the impacts of FcγRI in neuropathic pain was largely unknown. Here, we aimed to investigate the impacts of FcγRI in neuropathic pain through pain-related neurobehavioral studies and underlying mechanisms by biochemical methods in animal and cell models. Specifically, we first utilized the chronic constriction injury (CCI) rat model that displayed neuropathic pain related symptoms and signs, including thermal hyperalgesia and mechanical allodynia. These neurobehavioral defects were significantly attenuated by the anti-FcγRI antibody, which was associated with reduced levels of neuropeptide substance P, C3, and TNF-α. Furthermore, we validated our animal findings using the embryonically neural crest-originated PC12 cell model. We found that stimulation of the IgG immune complex led to increased levels of FcγRI and inflammatory mediators, which were attenuated by the anti-FcγRI antibody in these cells. Collectively, our results from animal and cell-based studies suggest that FcγRI is a critical player for peripheral nerve injury-induced neuropathic pain by mediating pain-related immunological events, which therefore may provide a new therapeutic target for protection against chronic pain.

Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain

1998 ◽  
Vol 62 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Janice L Arruda ◽  
Raymond W Colburn ◽  
Amy J Rickman ◽  
Maria D Rutkowski ◽  
Joyce A DeLeo
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Interleukin 6 ◽  
Peripheral Nerve Injury ◽  
Potential Role
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