Hyperalgesia due to nerve damage: role of nerve growth factor.
The hypothesis that nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) contribute to hyperalgesia resulting from nerve damage was tested in rats in which the sciatic nerve was partially transected on one side. Administration of antisera raised against NGF and BDNF relieved mechanical and thermal hyperalgesia in these animals. It has been suggested that NGF may elicit hyperalgesia by inducing mast cells to release algesic agents such as serotonin (5-HT). We found that degranulation of mast cells with compound 48/80 relieved mechanical and thermal hyperalgesia produced by nerve damage. We also found that local injection of the 5-HT2A and 5-HT3 receptor antagonists ketanserin and ICS 205-930 into the affected hind paw relieved mechanical hyperalgesia in a dose-dependent fashion. These findings support the idea that in this rat model of hyperalgesia due to peripheral nerve damage, NGF acts on mast cells to induce release of 5-HT, which sensitizes nociceptors. Hyperalgesia due to nerve injury and hyperalgesia due to inflammation may share some common features.
Theodosiou
M
M
School of Anatomy, University of New South Wales, Sydney NSW 2052, Australia School of Physiology and Pharmacology, University of New South Wales, Sydney NSW 2052, Australia Department of Physiology, Flinders University, Adelaide SA 5001, Australia.
Rush
A R
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Zhou
F X
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Hu
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Walker
S J
SJ
Tracey
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JD
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D007106:Immune Sera / Q000494:pharmacology; D007116:Immunization, Passive; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007650:Ketanserin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D009414:Nerve Growth Factors / Q000276:immunology / Q000502:physiology*; D020933:Neurotrophin 3; D009619:Nociceptors; D010525:Peripheral Nerves / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000601:surgery; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000077526:Tropisetron
D019208:Brain-Derived Neurotrophic Factor; D007106:Immune Sera; D007211:Indoles; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012702:Serotonin Antagonists; D012701:Serotonin; D000077526:Tropisetron; D007650:Ketanserin