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Nerve growth factor‐evoked nociceptor sensitization in pig skin in vivo
Author(s) -
Rukwied Roman,
Schley Marcus,
Forsch Elmar,
Obreja Otilia,
Dusch Martin,
Schmelz Martin
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22351
Subject(s) - sensitization , nociceptor , nerve growth factor , chemistry , axon reflex , sensory system , free nerve ending , erythema , capsaicin , trpv1 , reflex , biophysics , endocrinology , neuroscience , medicine , nociception , immunology , biology , transient receptor potential channel , biochemistry , receptor
Peripheral sensitization of skin nociceptors by nerve growth factor (NGF) was explored in pig skin in vivo. As an objective output measure, the area of axon‐reflex‐mediated erythema was assessed upon mechanical, thermal, chemical, and electrical stimuli delivered at 1, 3, and 7 days after i.d. injection of 1 μg NGF into the pig's back skin (n = 8). Pretreatment with NGF provoked a sensitization to mechanical (600 mN), thermal (10 sec 49°C) and chemical (15 μl, pH 3) stimuli that lasted for 7 days. No sensitization, however, was found in response to weak mechanical (100 mN), weak thermal (10 sec 45°C), or electrical stimuli. Irrespective of the skin pretreatment (NGF or PBS vehicle control), the area of electrically induced erythema decreased upon repetition (days 1–7) by 70% ( P < 0.05). Sensitization of sensory endings by NGF upon mechanical, heat, and chemical stimuli suggests recruitment of sensory transducer molecules [e.g., TRPV1, acid‐sensing ion channels (ASICs)]. In contrast, the gradual decrease in electrically induced erythema over 7 days might be attributable to axonal desensitization and possibly activity‐dependent down‐regulation of sodium channels. Thus, long‐lasting sensitization processes of nociceptor endings or axonal sodium channel desensitization mechanisms can be explored in the pig as a translational experimental animal model. © 2010 Wiley‐Liss, Inc.