Cutaneous Neuroimmune Interactions in Peripheral Neuropathic Pain States

Bidirectional interplay between the peripheral immune and nervous systems plays a crucial role in maintaining homeostasis and responding to noxious stimuli. This crosstalk is facilitated by a variety of cytokines, inflammatory mediators and neuropeptides. Dysregulation of this delicate physiological balance is implicated in the pathological mechanisms of various skin disorders and peripheral neuropathies. The skin is a highly complex biological structure within which peripheral sensory nerve terminals and immune cells colocalise. Herein, we provide an overview of the sensory innervation of the skin and immune cells resident to the skin. We discuss modulation of cutaneous immune response by sensory neurons and their mediators (e.g., nociceptor-derived neuropeptides), and sensory neuron regulation by cutaneous immune cells (e.g., nociceptor sensitization by immune-derived mediators). In particular, we discuss recent findings concerning neuroimmune communication in skin infections, psoriasis, allergic contact dermatitis and atopic dermatitis. We then summarize evidence of neuroimmune mechanisms in the skin in the context of peripheral neuropathic pain states, including chemotherapy-induced peripheral neuropathy, diabetic polyneuropathy, post-herpetic neuralgia, HIV-induced neuropathy, as well as entrapment and traumatic neuropathies. Finally, we highlight the future promise of emerging therapies associated with skin neuroimmune crosstalk in neuropathic pain.

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CGRP-immunoreactive cells supplying laryngeal sensory nerve fibres in the cat's nodose ganglion

The Journal of Laryngology & Otology ◽

10.1017/s0022215100124788 ◽

1993 ◽

Vol 107 (10) ◽

pp. 916-919 ◽

Cited By ~ 6

Author(s):

Yasumusa Tanaka ◽

Yoshikazu Yoshida ◽

Minoru Hirano

Keyword(s):

Sensory Neuron ◽

Sensory Neurons ◽

Sensory Nerve ◽

Middle Part ◽

Nodose Ganglion ◽

Sensory Innervation ◽

Sensory Cells ◽

Laryngeal Mucosa ◽

Peripheral Sensory ◽

Rostral Part

AbstractThrough a combination of retrograde staining by wheat germ agglutinin (WGA) and immunohistochemistry, calcitonin gene-related peptide (CGRP)-reactive sensory neurons projecting from the laryngeal mucosa were detected in the feline nodose ganglion. The size of the CGRP-immunoreactive cell which was regarded as a laryngeal sensory neuron, was about 60 ±m in diameter: the shape of the immunoreactive laryngeal sensory neuron was unipolar. CGRP-reacted laryngeal sensory cells were found in the rostral part of the nodose ganglion extending to the middle part. They aggregated in the most rostral part, were sparse in other parts and were approximately 50 per cent of WGA-reactive laryngeal sensory neurons in number. Our results suggest that this neurotransmitter might play an important role in laryngeal peripheral sensory innervation.

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Treatment of neurological complications in patients with type 2 diabetes mellitus at the stage of rehabilitation after COVID-19

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY ◽

10.22141/2224-0721.17.6.2021.243214 ◽

2021 ◽

Vol 17 (6) ◽

pp. 491-495

Author(s):

V.I. Pankiv

Keyword(s):

Neuropathic Pain ◽

Folic Acid ◽

Side Effects ◽

Nerve Regeneration ◽

Vitamin B1 ◽

Diabetic Polyneuropathy ◽

Neurological Complications ◽

Nerve Fibers ◽

Peripheral Neuropathic Pain ◽

Uridine Monophosphate

Although the predominant clinical manifestation of COVID-19 is a respiratory disease, various neurological symptoms are increasingly being diagnosed, in particular, diabetic polyneuropathy is diagnosed in most patients with diabetes, affecting large and small nerve fibers. Drugs that are traditionally used for neuropathic pain (tricyclic antidepressants, gabapentinoids, etc.), despite their positive effect in eliminating the symptoms of polyneuropathy, often cause side effects and do not impact nerve regeneration. Over the last decade, a group of nucleotides has been used quite actively. Additional information on the effects of this group of drugs was accumulated and there is a gradual transformation, including their compositions. Thus, recently the attention of researchers has been devoted to the study of the effectiveness of the combination of uridine, choline, vitamins B1, B6, B12, and folic acid, which is characterized by a fairly high safety profile and regenerative potential. The review highlights the mechanisms of action and results of clinical use of this combination. Uridine monophosphate, B vitamins, folic acid are involved in metabolic processes, enhancing nerve regeneration. This contributes to the development of indirect (secondary) analgesic effect. In addition, the data of new studies indicate the ability of uridine monophosphate derivatives to impact purinergic P2Y receptors, which causes a direct analgesic and direct regenerative effect. Studies have demonstrated the clinical efficacy of this combination in the main types of peripheral neuropathic pain. The combination did not cause side effects and was well tolerated. There was a reduction or complete withdrawal of concomitant analgesics against the background of improving the quality of life of patients. The combination of uridine, choline, vitamin B1, vitamin B6, vitamin B12, and folic acid is a very effective addition to the standard therapy of peripheral neuropathic pain of various genesis and rehabilitation after COVID-19.

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Neuropathic pain: mechanisms of development, principles of diagnostics and treatment

Pain medicine ◽

10.31636/pmjua.v4i2.1 ◽

2019 ◽

Vol 4 (2) ◽

pp. 4-32

Author(s):

Dmytro Dmytriiev ◽

Pylyp Prudius ◽

Olesia Zaletskaya ◽

Yevhen Lisak ◽

Yurii Rudnitsky ◽

...

Keyword(s):

Nervous System ◽

Neuropathic Pain ◽

Pain Syndrome ◽

Diabetic Polyneuropathy ◽

Pain Mechanisms ◽

Peripheral Neuropathic Pain ◽

Pain Pathways ◽

Mechanisms Of Development ◽

Somatosensory Nervous System ◽

Cause Of Pain

Neuropathic pain is a pain caused by a disease or focal damage to the somatosensory nervous system. The prevalence of chronic pain with neuropathic features in different countries is estimated at 7–10 %. Damages to the nervous system can occur at the level of peripheral nerves, plexus and dorsal roots (peripheral neuropathic pain) or spinal cord and brain (central neuropathic pain). Neuropathic pain is based on pathological activation of pain pathways. Neuropathic pain occurs with diabetic polyneuropathy more often than with all polyneuropathies of another etiology. Hyperglycemia is the major cause of chronic diabetes mellitus and its progression. Since the cause of pain can rarely be cured, treatment is usually symptomatic. Neuropathic pain is generally poorly controlled by analgesics. NB management is started with conservative pharmacotherapy before applying invasive analgesia. Although there are many drugs that can be used in patients with DPN, monotherapy can not always stop pain syndrome. In addition, the patient may not tolerate the full therapeutic dose of the drug. All this dictates the need for combination therapy.

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Cutaneous Nerve Fibers Participate in the Progression of Psoriasis by Linking Epidermal Keratinocytes and Immunocytes

10.21203/rs.3.rs-1141935/v1 ◽

2021 ◽

Author(s):

Si-Qi Chen ◽

Xue-Yan Chen ◽

Ying-Zhe Cui ◽

Bing-Xi Yan ◽

Yuan Zhou ◽

...

Keyword(s):

Immune Cells ◽

Botulinum Toxin A ◽

Sensory Nerve ◽

Vital Role ◽

Nerve Fibers ◽

Cutaneous Nerve ◽

Epidermal Keratinocytes ◽

New Treatment ◽

Peripheral Sensory ◽

Psoriatic Lesions

Abstract Recent studies have illustrated that psoriatic lesions are innervated by dense sensory nerve fibers. Psoriatic plaques appeared to improve after central or peripheral nerve injury. Therefore, the nervous system may play a vital role in psoriasis. We aimed to clarify the expression of nerve fibers in psoriasis and their relationship with immune cells and keratinocytes, and to explore the effect of skin nerve impairment. Our results illustrated that nerve fibers in psoriatic lesions increased and were closely innervated around immune cells and keratinocytes. RNA-seq analysis showed that peripheral sensory nerve-related genes were disrupted in psoriasis. In spinal cord hemi-section mice, sensory impairment improved psoriasiform dermatitis and inhibited the abnormal proliferation of keratinocytes. Botulinum toxin A alleviated psoriasiform dermatitis by inhibiting the secretion of calcitonin gene-related peptide. Collectively, cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes. Neurological intervention may be a new treatment strategy for psoriasis.

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