Abstract
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.
Highlights
Neuropathic pain is defined by the International Association for the Study of Pain as pain caused by a lesion or disease of the somatosensory nervous system [1]
The preclinical data support this idea, but, in clinical practice, only a few of peripheral mechanisms of Neuropathic pain (NP) are currently addressed [10,11,12,13,14] This review of literature is aimed at presenting the available evidence from preclinical and clinical studies on the peripheral mechanisms of NP with special focus on interactions between neuronal and non-neuronal cells, the molecular targets for topical analgesics, and clinical implications for topical administration in NP management
Local injections of BTX-A are recommended as the third-line treatment in patients with Localized neuropathic pain (LNP), but scientific evidence for its use is weak [109,110]
Summary
Neuropathic pain is defined by the International Association for the Study of Pain as pain caused by a lesion or disease of the somatosensory nervous system [1]. Pharmaceuticals 2021, 14, 77 suggested that a more peripheral lesion induces more localized signs and symptoms of NP [6]. In 2010, the first definition of localized neuropathic pain was proposed, aiming at description of a special type of NP, which is caused primarily by the injury of peripheral nervous system. The preclinical data support this idea, but, in clinical practice, only a few of peripheral mechanisms of NP are currently addressed [10,11,12,13,14] This review of literature is aimed at presenting the available evidence from preclinical and clinical studies on the peripheral mechanisms of NP with special focus on interactions between neuronal and non-neuronal cells, the molecular targets for topical analgesics, and clinical implications for topical administration in NP management.
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