Spinal 5-HT3 receptors facilitate behavioural hypersensitivity induced by elevated calcium channel alpha-2-delta-1 protein.
BACKGROUND
Peripheral nerve injury induces up-regulation of the calcium channel alpha-2-delta-1 proteins in the dorsal root ganglia and dorsal spinal cord that correlates with neuropathic pain development. Similar behavioural hypersensitivity was also observed in injury-free transgenic (TG) mice over-expressing the alpha-2-delta-1 proteins in neuronal tissues. To investigate pathways regulating alpha-2-delta-1 protein-mediated behavioural hypersensitivity, we examined whether spinal serotonergic 5-HT3 receptors are involved similarly in the modulation of behavioural hypersensitivity induced by either peripheral nerve injury in a nerve injury model or neuronal alpha-2-delta-1 over-expression in the TG model.


METHODS
The effects of blocking behavioural hypersensitivity in these two models by intrathecal or systemic injections of 5-HT3 receptor antagonist, ondansetron, were compared.


RESULTS
Our data indicated that the TG mice displayed similar behavioural hypersensitivities to non-painful mechanical stimulation (tactile allodynia) and painful thermal stimulation (thermal hyperalgesia) as that observed in the nerve injury model. Interestingly, tactile allodynia and thermal hyperalgesia in both models can be blocked similarly by intrathecal, but not systemic, injection of ondansetron.


CONCLUSIONS
Our data suggest that spinal 5-HT3 receptors are likely to play a role in alpha-2-delta-1-mediated behavioural hypersensitivities through a descending serotonergic facilitation.
Department of Anesthesiology & Perioperative Care School of Medicine, University of California, Irvine, USA.
E Y
EY
Chang
X
X
Chen
A
A
Sandhu
C-Y
CY
Li
Z D
ZD
Luo
D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009437:Neuralgia / Q000378:metabolism*; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology; D010147:Pain Measurement; D010812:Physical Stimulation; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
C512066:CACNA2D1 protein, mouse; D015220:Calcium Channels; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D017294:Ondansetron