Abstract
The skin acts as a complex sensory organ. The emerging new data on peripheral pain mechanisms from within the skin is presented. This data has led to new insights into the potential pain mechanisms for various pain conditions including neuropathic pain (from small fiber neuropathies) and Complex Regional Pain Syndrome. The somatosensory neurons that innervate our skin constantly update our brains on the objects and environmental factors that surround us. Cutaneous sensory neurons expressing nociceptive receptors such as transient receptor potential vanilloid 1 channels and voltage-gated sodium channels are critical for pain transmission. Epidermal cells (such as keratinocytes, Langerhans cells, and Merkel cells) express sensor proteins and neuropeptides; these regulate the neuroimmunocutaneous system and participate in nociception and neurogenic inflammation. In the past two decades, there has been widespread use of modalities such as punch skin biopsies, quantitative sensory testing, and laser-evoked potentials to evaluate small caliber nerve fibers. This paper explores these laboratory techniques as well as the phenomenon of small fiber neuropathy. Treatment using transdermal drug delivery is discussed. There is potential for these findings to predict treatment outcomes in clinical practice and to develop new therapies for different pain conditions. These findings should enhance the physician's ability to evaluate and treat diverse types of pain.
Highlights
The skin has homeostatic and immunologic barrier functions, but acts as a complex sensory organ as well [1]
New data concerning peripheral pain mechanisms from within the skin have led to new insight into the potential pain mechanisms for various pain conditions including neuropathic pain syndromes such as diabetic neuropathy and Complex Regional Pain Syndrome
Keratinocytes have a close anatomic relationship with peripheral nerves; they have transient receptor potential vanilloid 1 (TRPV1) channels and transient receptor potential ankyrin 1 (TRPA1) channels on their surface [1, 4]
Summary
The skin has homeostatic and immunologic barrier functions, but acts as a complex sensory organ as well [1]. The neuroimmunocutaneous system (NICS) is responsible for the cutaneous sensations of touch, pressure, temperature, and pain This sensory transduction occurs via primary afferent nerves following reciprocated signals between neuronal and nonneuronal skin cells of the NICS [1]. The pain is regional (not in a specific nerve territory or dermatome); it usually has a distal predominance of abnormal sensory, motor, sudomotor, vasomotor, and/or trophic findings It has signs of central sensitisation such as allodynia and hyperalgesia. The activation of cutaneous nociceptors can induce retrograde depolarisation of small-diameter primary afferents, causing release of neuropeptides such as substance P and CGRP from sensory terminals in the skin These neuropeptides evoke vasodilation and protein extravasation in the tissue [26]. Understanding the relationship between body perception disturbance, pain, and tactile acuity might provide insight into alternative avenues for treatment [28]
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