Nociceptin/orphanin FQ opioid peptide‐receptor expression in pachyonychia congenita

Pan, Baohan; Schröder, Wolfgang; Jostock, Ruth; Schwartz, Mary E.; Rosson, Gedge D.; Polydefkis, Michael

doi:10.1111/jns.12288

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…Many treatments for PC, such as Botox injections [60, 61], focus on pain management. Although some research has focused on treatment of the underlying cause, such as reducing expression of keratin alleles [62, 63], success has only been reported in small group case reports.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Distinctions in the Management, Patient Impact, and Clinical Profiles of Pachyonychia Congenita Subtypes

Lipner

2021

Skin Appendage Disord

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Introduction: Pachyonychia congenita (PC) is a rare dermatosis that confers lifelong physical and emotional morbidities in affected patients. However, the clinical findings, treatments, and psychosocial impact of this disease have not been adequately described. The International PC Research Registry (IPCRR), a multinational initiative to collect data on PC patients, has allowed an opportunity to distinguish the salient features of this disease. We aimed to characterize the breadth and extent of nail disease, treatments, and quality of life in PC patients, and to describe any significant differences in clinical presentation or treatment of PC subtypes. Methods: The most recent IPCRR patient survey data consisting of an 857-response questionnaire and a 102-response addendum were analyzed in a retrospective analysis. The survey data were collected as part of a multinational, multicenter initiative and comprise the largest representative population of PC to date. Participants (survey respondents) were included in the study based on questionnaire responses and a genetic confirmation of having a PC subtype. Results: A total of 857 survey responses were collected. Genetic variations among PC subtypes influence nail disease onset and severity of symptoms. Nail disease negatively impacts patients’ emotional health, especially during the adolescent and young adult years. Nail treatment tools vary little in terms of effectiveness and acquired infection rates. Conclusion and Discussion: Patients with different PC subtypes have distinct clinical nail presentations and psychosocial impact. Genetic testing should be used to confirm PC diagnoses. Further characterization of PC, especially the rarer subtypes, may allow for more individualized patient education.

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Section: Discussion/conclusionmentioning

confidence: 99%

Distinctions in the Management, Patient Impact, and Clinical Profiles of Pachyonychia Congenita Subtypes

Lipner

2021

Skin Appendage Disord

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“…In patients with NP due to pachyonychia congenita, overexpression of NOR on epidermal keratinocytes and epidermal and dermal nerve fibers has been demonstrated [284]. Recently, NOR has been identified on human blood granulocytes as well [285].…”

Section: Treatments Acting On Peripheral Opioid Receptorsmentioning

confidence: 99%

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

et al. 2021

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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.

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“…The preclinical studies showed stimulation of keratinocytes alone to be sufficient to induce neuronal hyperexcitability and pain behaviour in animals [87,88]. According to preclinical data, keratinocytes express several receptors and ion channels, playing role in nociception, such as Nav (Nav 1.1,1.2, 1.5,1.6,1.7,1.8), TRP (TRPV1-4), neurokinin 1 receptor (NK1-receptor, NK1R), TLR, interleukin receptors, α1-AR, endothelin1 receptors (ET1), calcitonin receptor-like receptor (CRLR), CB receptors, OR, NOP (nociceptin-orphanin opioid peptide) receptors (NOP-R), VGCC, NMDAR, and GABAR to mention a few [89][90][91][92][93][94][95][96]. The role of keratinocyte receptors and their overexpression in nociception has been confirmed in clinical observations.…”

Section: 4 the Role Of Skin Cells In Peripheral Mechanisms Of Npmentioning

confidence: 99%

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

et al. 2021

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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.

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Nociceptin/orphanin FQ opioid peptide‐receptor expression in pachyonychia congenita

Cited by 8 publications

References 35 publications

Distinctions in the Management, Patient Impact, and Clinical Profiles of Pachyonychia Congenita Subtypes

Distinctions in the Management, Patient Impact, and Clinical Profiles of Pachyonychia Congenita Subtypes

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

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

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