Referenced in: none

Automatically associated channels: BKβ

Title: Inflammation and hypersensitivity in the context of the sensory functions of axonal membranes: what are the molecular mechanisms?

Authors: Susanne K Sauer, Peter W Reeh

Journal, date & volume: Dig Dis, 2009 , 27 Suppl 1, 11-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20203492

Abstract
The axonal membrane of unmyelinated sensory nerve fibers is well equipped with different molecular transducer molecules that establish specific sensitivities, the capacity for sensitization by inflammation and generation of ectopic action potentials that contribute to spinal sensitization, leading to projected pain, allodynia and hyperalgesia.We studied the sensory properties of unmyelinated axons in the midnerve by measuring stimulated neuropeptide release, recording from primary afferents and eliciting projected pain by stimulation of a surgically exposed superficial radial nerve in a conscious human subject.Capsaicin (TRPV1) receptor channels are expressed along the axonal membrane and respond to acidic, thermal and capsaicin stimulation with a graded and calcium-dependent calcitonin gene-related peptide release. These responses can be facilitated by bradykinin or prostaglandin, indicating functional BK and EP receptors along the axonal membrane. Sensitizing effects are lost in preparations from TRPV1 knockout mice. In the isolated vagus nerve, representing visceral innervation, the endovanilloid/endocannabinoid anandamide induced or sensitized calcitonin gene-related peptide release by activation of TRPV1. Our electrophysiological recordings revealed ectopic generation of action potentials. Intact unmyelinated axons showed sensory capacities that resembled those of their individual cutaneous nociceptive terminals, with respect to noxious heat sensitivity. In the human subject, noxious heat stimulation of the exposed skin nerve evoked intense burning pain sensation in the innervation territory.Different lines of evidence indicate that nociceptive axons exhibit essential parts of the signal transduction and spike generation machinery. When amplified (e.g. by inflammatory mediators), this axonal sensitivity may become a source of neuropathic pain.