Antibody directed against GD(2) produces mechanical allodynia, but not thermal hyperalgesia when administered systemically or intrathecally despite its dependence on capsaicin sensitive afferents.
Anti-GD(2) antibodies have been shown to be effective for immunotherapy of neuroblastoma and other GD(2) enriched malignancies. Infusion of anti-GD(2) antibodies frequently causes spontaneous pain and allodynia for the duration of the immunotherapy and occasionally longer lasting neuropathic pain. Bolus intravenous injection of anti-GD(2) in rats initiates mechanical allodynia as measured by withdrawal threshold of the hindpaws. In this study, thermal thresholds were measured prior to and for up to 6 h following systemic anti-GD(2) administration in adult rats. In addition, both thermal and mechanical thresholds were tested following intrathecal administration of anti-GD(2) and IgG(2a). Murine anti-GD(2) elicited mechanical allodynia when administered into either the vasculature or the intrathecal space. Effective systemic doses were 1--3 mg/kg as previously shown. Intrathecally, optimal doses ranged from 0.01 to 0.1 ng; a higher dose was ineffective. Thermal hyperalgesia was not observed via either route of administration. Intrathecal pretreatment 48--72 h prior to the experiment with capsaicin at doses sufficient to cause a 50% depletion of dorsal horn CGRP, caused a total blockade of the mechanical allodynia indicating an involvement of peptidergic fine afferent fibers. It is likely that the antibody reacts with an antigen on peripheral nerve and/or myelin to initiate its effect. The lack of observed thermal hyperalgesia is surprising especially in light of the capsaicin-associated blockade, however, it is consistent with several other immune system related models of pain.
Sorkin
L S
LS
Anesthesiology Research Laboratories, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0818, USA. lsorkin@ucsd.edu
Yu
A L
AL
Junger
H
H
Doom
C M
CM
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D005732:Gangliosides / Q000037:antagonists & inhibitors* / Q000276:immunology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D007262:Infusions, Intravenous; D007278:Injections, Spinal; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D005732:Gangliosides; C019403:ganglioside, GD2; D002211:Capsaicin