Current Pain and Headache Reports

, Volume 14, Issue 3, pp 179–188 | Cite as

Role of Small-Fiber Afferents in Pain Mechanisms With Implications on Diagnosis and Treatment



Numerous mechanisms are implicated in the perception of pain. Although many anatomical, molecular, and functional components have been identified, a comprehensive and integrated theory of pain perception has yet to be firmly established that fits the diverse clinical experience. Acute pain involves the activation of several varieties of small primary sensory neurons, collectively termed nociceptors, which have small-caliber unmyelinated or myelinated axons (C and Aδ fibers, respectively) that innervate all body tissues. They are stimulated by noxious stimuli that activate ion channels on the endings either directly or through the release of cytokines from damaged or stressed tissues. A variety of drugs successfully treats acute pain by targeting these ion channels or cytokine interactions. Paradoxically, several chronic neuropathic pain conditions are associated with a loss of small-caliber axons and have an unpredictable and poor response to current drugs, especially at doses that do not cause severe side effects. In an attempt to further an integrated theory of pain perception, this review focuses upon the presumed role of small-caliber innervation, particularly to the epidermis and cutaneous vasculature, and the clinical manifestations, diagnosis, and treatment of pathologies of this innervation.


Neuropathic Chronic Sensory innervation DRG FNE Epidermis Keratinocytes Endothelium Smooth muscle Sweat gland Piloneural Neurovascular Homeostasis Nociceptors 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Center for Neuropharmacology and Neuroscience (MC136)Albany Medical CollegeAlbanyUSA
  2. 2.Integrated Tissue Dynamics, LLCRensselaerUSA

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