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Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse.
Br J Pharmacol. 2005 Mar; 144(5):703-14.BJ

Abstract

1. To gain further insight into the mechanisms underlying the antihyperalgesic and antiallodynic actions of gabapentin, a chronic pain model was prepared by partially ligating the sciatic nerve in mice. The mice then received systemic or local injections of gabapentin combined with either central noradrenaline (NA) depletion by 6-hydroxydopamine (6-OHDA) or alpha-adrenergic receptor blockade. 2. Intraperitoneally (i.p.) administered gabapentin produced antihyperalgesic and antiallodynic effects that were manifested by elevation of the withdrawal threshold to a thermal (plantar test) or mechanical (von Frey test) stimulus, respectively. 3. Similar effects were obtained in both the plantar and von Frey tests when gabapentin was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.), suggesting that it acts at both supraspinal and spinal loci. This novel supraspinal analgesic action of gabapentin was only obtained in ligated neuropathic mice, and gabapentin (i.p. and i.c.v.) did not affect acute thermal and mechanical nociception. 4. In mice in which central NA levels were depleted by 6-OHDA, the antihyperalgesic and antiallodynic effects of i.p. and i.c.v. gabapentin were strongly suppressed. 5. The antihyperalgesic and antiallodynic effects of systemic gabapentin were reduced by both systemic and i.t. administration of yohimbine, an alpha2-adrenergic receptor antagonist. By contrast, prazosin (i.p. or i.t.), an alpha1-adrenergic receptor antagonist, did not alter the effects of gabapentin. 6. It was concluded that the antihyperalgesic and antiallodynic effects of gabapentin are mediated substantially by the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors.

Authors+Show Affiliations

Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. mitana@phar.nagoya-cu.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15678083

Citation

Tanabe, Mitsuo, et al. "Role of Descending Noradrenergic System and Spinal Alpha2-adrenergic Receptors in the Effects of Gabapentin On Thermal and Mechanical Nociception After Partial Nerve Injury in the Mouse." British Journal of Pharmacology, vol. 144, no. 5, 2005, pp. 703-14.
Tanabe M, Takasu K, Kasuya N, et al. Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse. Br J Pharmacol. 2005;144(5):703-14.
Tanabe, M., Takasu, K., Kasuya, N., Shimizu, S., Honda, M., & Ono, H. (2005). Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse. British Journal of Pharmacology, 144(5), 703-14.
Tanabe M, et al. Role of Descending Noradrenergic System and Spinal Alpha2-adrenergic Receptors in the Effects of Gabapentin On Thermal and Mechanical Nociception After Partial Nerve Injury in the Mouse. Br J Pharmacol. 2005;144(5):703-14. PubMed PMID: 15678083.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse. AU - Tanabe,Mitsuo, AU - Takasu,Keiko, AU - Kasuya,Noriyo, AU - Shimizu,Shinobu, AU - Honda,Motoko, AU - Ono,Hideki, PY - 2005/1/29/pubmed PY - 2005/9/24/medline PY - 2005/1/29/entrez SP - 703 EP - 14 JF - British journal of pharmacology JO - Br J Pharmacol VL - 144 IS - 5 N2 - 1. To gain further insight into the mechanisms underlying the antihyperalgesic and antiallodynic actions of gabapentin, a chronic pain model was prepared by partially ligating the sciatic nerve in mice. The mice then received systemic or local injections of gabapentin combined with either central noradrenaline (NA) depletion by 6-hydroxydopamine (6-OHDA) or alpha-adrenergic receptor blockade. 2. Intraperitoneally (i.p.) administered gabapentin produced antihyperalgesic and antiallodynic effects that were manifested by elevation of the withdrawal threshold to a thermal (plantar test) or mechanical (von Frey test) stimulus, respectively. 3. Similar effects were obtained in both the plantar and von Frey tests when gabapentin was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.), suggesting that it acts at both supraspinal and spinal loci. This novel supraspinal analgesic action of gabapentin was only obtained in ligated neuropathic mice, and gabapentin (i.p. and i.c.v.) did not affect acute thermal and mechanical nociception. 4. In mice in which central NA levels were depleted by 6-OHDA, the antihyperalgesic and antiallodynic effects of i.p. and i.c.v. gabapentin were strongly suppressed. 5. The antihyperalgesic and antiallodynic effects of systemic gabapentin were reduced by both systemic and i.t. administration of yohimbine, an alpha2-adrenergic receptor antagonist. By contrast, prazosin (i.p. or i.t.), an alpha1-adrenergic receptor antagonist, did not alter the effects of gabapentin. 6. It was concluded that the antihyperalgesic and antiallodynic effects of gabapentin are mediated substantially by the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/15678083/Role_of_descending_noradrenergic_system_and_spinal_alpha2_adrenergic_receptors_in_the_effects_of_gabapentin_on_thermal_and_mechanical_nociception_after_partial_nerve_injury_in_the_mouse_ L2 - https://doi.org/10.1038/sj.bjp.0706109 DB - PRIME DP - Unbound Medicine ER -