Spinal sensitization mechanism in vincristine-induced hyperalgesia in mice.
Our aim was to investigate the possible involvement of spinal voltage-dependent Ca(2+) channels (VDCCs) in vincristine-induced hyperalgesia and also to characterize this hyperalgesic state in the spinal cord. Mice receiving vincristine displayed significantly lower mechanical nociceptive thresholds than controls. Intrathecal omega-conotoxin GVIA (an N-type blocker) produced dose-dependent inhibition of the mechanical nociception, its antinociceptive effect being greater in vincristine-treated mice than in controls. The antinociception of omega-agatoxin IVA (a P/Q-type blocker) and calciseptine (an L-type blocker) were both slightly, but not significantly greater in vincristine-treated mice. An N-methyl-D-aspartate-receptor antagonist but not a tachykinin-NK1-receptor antagonist produced greater antinociception in vincristine-treated mice. These results suggest that vincristine-induced hyperalgesia involves a sensitization of the spinal processing of mechanical sensory information via a mechanism involving N-type but not P/Q- or L-type VDCCs. A spinal glutamatergic pathway also appears to be involved in this hyperalgesia.
Fukuizumi
Tadaoki
T
Department of Physiological Science & Molecular Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
Ohkubo
Tsuyako
T
Kitamura
Kenji
K
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051379:Mice; D064729:Neurokinin-1 Receptor Antagonists; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D011812:Quinuclidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000503:physiopathology*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014750:Vincristine / Q000633:toxicity*; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004546:Elapid Venoms; D064729:Neurokinin-1 Receptor Antagonists; D011812:Quinuclidines; D016194:Receptors, N-Methyl-D-Aspartate; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C076851:L 703606; C067971:calciseptine; D014750:Vincristine; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine