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Intrathecal gabapentin does not act as a hyperpolarization-activated cyclic nucleotide-gated channel activator in the rat formalin test.
Eur J Anaesthesiol. 2009 Oct; 26(10):821-4.EJ

Abstract

BACKGROUND AND OBJECTIVE

Gabapentin, an anticonvulsant with analgesic effect, has been reported to be an activator of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In this study, we tested the effect of intrathecal ZD7288, an HCN channel inhibitor, and its interaction with intrathecal gabapentin in the rat formalin test.

METHODS

Male Sprague-Dawley rats (250-300 g) with an intrathecal catheter were intraplantarly injected with formalin (5% formaldehyde, 50 microl) in the right hindpaw. Ten minutes before formalin injection, gabapentin (100 or 200 microg) was given intrathecally. ZD7288 (50 microg) was administered intrathecally 10 min before paw formalin injection or intrathecal gabapentin. The paw flinch numbers in 1 min were counted at the first minute and every 5 min for 1 h after formalin injection.

RESULTS

Biphasic flinching responses were induced by formalin and monitored at 0-9 min (phase 1) and 10-60 min (phase 2) after formalin injection. Gabapentin (100 and 200 microg), given intrathecally 10 min before formalin injection, attenuated the flinching response during phase 2 of the formalin test. ZD7288 (50 microg), given intrathecally 10 min before formalin injection or intrathecal gabapentin injection, did not attenuate the formalin-induced flinching response or reverse gabapentin-induced analgesia.

CONCLUSION

Our data suggest that activation of spinal or dorsal root ganglion HCN channels or both is not involved in formalin-induced pain, and intrathecal gabapentin does not act as an HCN channel activator to achieve its antinociceptive effect in the formalin test.

Authors+Show Affiliations

Department of Anesthesiology, Mackay Memorial Hospital, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19322095

Citation

Lin, Chih-Fu, et al. "Intrathecal Gabapentin Does Not Act as a Hyperpolarization-activated Cyclic Nucleotide-gated Channel Activator in the Rat Formalin Test." European Journal of Anaesthesiology, vol. 26, no. 10, 2009, pp. 821-4.
Lin CF, Tsaur ML, Lin CS, et al. Intrathecal gabapentin does not act as a hyperpolarization-activated cyclic nucleotide-gated channel activator in the rat formalin test. Eur J Anaesthesiol. 2009;26(10):821-4.
Lin, C. F., Tsaur, M. L., Lin, C. S., Chen, C. C., Huang, Y. J., & Cheng, J. K. (2009). Intrathecal gabapentin does not act as a hyperpolarization-activated cyclic nucleotide-gated channel activator in the rat formalin test. European Journal of Anaesthesiology, 26(10), 821-4. https://doi.org/10.1097/EJA.0b013e32832a991a
Lin CF, et al. Intrathecal Gabapentin Does Not Act as a Hyperpolarization-activated Cyclic Nucleotide-gated Channel Activator in the Rat Formalin Test. Eur J Anaesthesiol. 2009;26(10):821-4. PubMed PMID: 19322095.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrathecal gabapentin does not act as a hyperpolarization-activated cyclic nucleotide-gated channel activator in the rat formalin test. AU - Lin,Chih-Fu, AU - Tsaur,Meei-Ling, AU - Lin,Chia-Shiang, AU - Chen,Chien-Chuan, AU - Huang,Yung-Jen, AU - Cheng,Jen-Kun, PY - 2009/3/27/entrez PY - 2009/3/27/pubmed PY - 2009/12/16/medline SP - 821 EP - 4 JF - European journal of anaesthesiology JO - Eur J Anaesthesiol VL - 26 IS - 10 N2 - BACKGROUND AND OBJECTIVE: Gabapentin, an anticonvulsant with analgesic effect, has been reported to be an activator of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In this study, we tested the effect of intrathecal ZD7288, an HCN channel inhibitor, and its interaction with intrathecal gabapentin in the rat formalin test. METHODS: Male Sprague-Dawley rats (250-300 g) with an intrathecal catheter were intraplantarly injected with formalin (5% formaldehyde, 50 microl) in the right hindpaw. Ten minutes before formalin injection, gabapentin (100 or 200 microg) was given intrathecally. ZD7288 (50 microg) was administered intrathecally 10 min before paw formalin injection or intrathecal gabapentin. The paw flinch numbers in 1 min were counted at the first minute and every 5 min for 1 h after formalin injection. RESULTS: Biphasic flinching responses were induced by formalin and monitored at 0-9 min (phase 1) and 10-60 min (phase 2) after formalin injection. Gabapentin (100 and 200 microg), given intrathecally 10 min before formalin injection, attenuated the flinching response during phase 2 of the formalin test. ZD7288 (50 microg), given intrathecally 10 min before formalin injection or intrathecal gabapentin injection, did not attenuate the formalin-induced flinching response or reverse gabapentin-induced analgesia. CONCLUSION: Our data suggest that activation of spinal or dorsal root ganglion HCN channels or both is not involved in formalin-induced pain, and intrathecal gabapentin does not act as an HCN channel activator to achieve its antinociceptive effect in the formalin test. SN - 1365-2346 UR - https://www.unboundmedicine.com/medline/citation/19322095/Intrathecal_gabapentin_does_not_act_as_a_hyperpolarization_activated_cyclic_nucleotide_gated_channel_activator_in_the_rat_formalin_test_ L2 - https://doi.org/10.1097/EJA.0b013e32832a991a DB - PRIME DP - Unbound Medicine ER -