Nerve growth factor induces mechanical allodynia associated with novel A fibre-evoked spinal reflex activity and enhanced neurokinin-1 receptor activation in the rat.
A single dose of nerve growth factor (NGF, 1 microgram/g, i.p.) administered to rats aged between postnatal days (PND) 12 and 14 resulted in a behavioural hypersensitivity of the hindlimb flexion withdrawal reflex to mechanical stimuli which developed 2 h after NGF and remained significant for 24 h. Heat hyperalgesia occurred some 4 h following NGF injection and lasted for 24 h. Isolated spinal cords were prepared from animals treated with NGF and were maintained in vitro for physiological and pharmacological analysis of lumbar spinal reflex activity. Repetitive, low-frequency group I/II A beta-fibre stimulation evoked a novel wind-up response after NGF injection similar to that produced by C-fiber group III/IV stimulation in normal animals. The neurokinin-1 (NK1) receptor antagonist RP67580 reduced the C fiber-evoked responses following NGF treatment but not in naive preparations. The novel A beta fiber-evoked wind-up response was also reduced by RP67580. The NGF-induced changes in NK1 receptor responses occurred in the absence of any detectable changes in either spinal cord NK1 receptor dose-response relationships or NK1 receptor mRNA levels. These findings are likely to be related to the behavioural allodynia observed in the present study and to central excitability changes observed after chronic inflammation where NGF levels are increased.
Sandoz Institute for Medical Research, 5 Gower Place, London WC1E 6BT UK Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA.
S W N
SWN
Thompson
A
A
Dray
K E
KE
McCarson
J E
JE
Krause
L
L
Urban
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D006614:Hindlimb / Q000294:innervation; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008161:Lumbosacral Region; D016202:N-Methylaspartate / Q000494:pharmacology; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009437:Neuralgia / Q000503:physiopathology*; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D012018:Reflex / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects*; D013314:Stress, Mechanical
D000700:Analgesics; D007211:Indoles; D054833:Isoindoles; D009414:Nerve Growth Factors; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D016202:N-Methylaspartate