Nerve growth factor-evoked nociceptor sensitization in pig skin in vivo.
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 microg NGF into the pig's back skin (n = 8). Pretreatment with NGF provoked a sensitization to mechanical (600 mN), thermal (10 sec 49 degrees C) and chemical (15 microl, 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 degrees 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.
Rukwied
Roman
R
University Clinics of Anaesthesiology and Intensive Care Medicine, University Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. roman.rukwied@medma.uni-heidelberg.de
Schley
Marcus
M
Forsch
Elmar
E
Obreja
Otilia
O
Dusch
Martin
M
Schmelz
Martin
M
D000818:Animals; D001369:Axons / Q000502:physiology; D001415:Back / Q000503:physiopathology; D004558:Electric Stimulation; D004890:Erythema / Q000503:physiopathology*; D005260:Female; D020932:Nerve Growth Factor / Q000378:metabolism*; D009619:Nociceptors / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation; D012018:Reflex / Q000502:physiology; D012879:Skin Physiological Phenomena; D013552:Swine; D013696:Temperature; D013997:Time Factors
D020932:Nerve Growth Factor