An animal model of pain produced by systemic administration of an immunotherapeutic anti-ganglioside antibody.
For the management of pediatric neuroblastoma, a promising experimental treatment includes slow systemic infusion of a human/ mouse chimeric monoclonal antibody against the GD2 ganglioside. Beneficial actions are however, accompanied by severe pain and altered cardiovascular tone. The pain is conventionally controllable with moderate to relatively high doses of intravenous morphine. An animal model was established to examine the change in nociceptive threshold produced by anti-GD2-antibody. Rats given bolus injections of antibody through an in-dwelling jugular catheter developed a quantifiable mechanical allodynia. At higher doses, allodynia and touch evoked agitation began within the first 15-min test interval, was maximal within the first hour, and for some doses was still present, although greatly reduced at 24 and 48 h. Rapid administration of antibody led to an increase in mean resting blood pressure of 12 mmHg +/- 1.8 (P < or = 0.02) and the development of a prolonged cardiovascular response to an otherwise innocuous stimulus. These observations demonstrate that the pain associated with monoclonal antibody treatment can be modeled in animals. This approach has potential for defining the pharmacology of the allodynia and ways in which the pain state may be ameliorated.
Slart
R
R
University of Groningen, The Netherlands.
Yu
A L
AL
Yaksh
T L
TL
Sorkin
L S
LS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D005732:Gangliosides / Q000276:immunology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology / Q000523:psychology; D007167:Immunotherapy / Q000009:adverse effects*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D005732:Gangliosides; C019403:ganglioside, GD2