Contributed equally to the study.
Spinal 5-HT3 receptors facilitate behavioural hypersensitivity induced by elevated calcium channel alpha-2-delta-1 protein
Version of Record online: 5 OCT 2012
© 2012 European Federation of International Association for the Study of Pain Chapters
European Journal of Pain
Volume 17, Issue 4, pages 505–513, April 2013
How to Cite
Chang, E.Y., Chen, X., Sandhu, A., Li, C.-Y. and Luo, Z.D. (2013), Spinal 5-HT3 receptors facilitate behavioural hypersensitivity induced by elevated calcium channel alpha-2-delta-1 protein. European Journal of Pain, 17: 505–513. doi: 10.1002/j.1532-2149.2012.00221.x
Supported in part by NIH grants: NS064341 and DE021847 (Z.D. Luo). E.Y. Chang is supported by a NIH K12 fellowship (K12HD001097) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development.
Conflicts of interest
- Issue online: 14 MAR 2013
- Version of Record online: 5 OCT 2012
- Manuscript Accepted: 9 AUG 2012
- NIH. Grant Numbers: NS064341, DE021847
- NIH K12. Grant Number: K12HD001097
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.
The effects of blocking behavioural hypersensitivity in these two models by intrathecal or systemic injections of 5-HT3 receptor antagonist, ondansetron, were compared.
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.
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.