Intrathecally administered gabapentin inhibits formalin-evoked nociception and the expression of Fos-like immunoreactivity in the spinal cord of the rat

Megumi Kaneko; Christine Mestre; Edgard H Sánchez; Donna L Hammond

doi:10.1016/S0022-3565(24)35347-9

Back

Intrathecally administered gabapentin inhibits formalin-evoked nociception and the expression of Fos-like immunoreactivity in the spinal cord of the rat

Journal article

Peer reviewed

Intrathecally administered gabapentin inhibits formalin-evoked nociception and the expression of Fos-like immunoreactivity in the spinal cord of the rat

Megumi Kaneko, Christine Mestre, Edgard H Sánchez and Donna L Hammond

The Journal of pharmacology and experimental therapeutics, Vol.292(2), pp.743-751

02/2000

DOI: 10.1016/S0022-3565(24)35347-9

PMID: 10640314

View Online

Abstract

In the present study, we investigated the effects of intrathecal gabapentin on nociceptive behaviors and the numbers of spinal Fos-like immunoreactive (Fos-LI) neurons evoked by injection of 0.25 to 2.5% formalin in the hindpaw of the rat. Pretreatment with gabapentin dose dependently decreased flinches and weighted pain scores in phase 2, but not phase 1, at each concentration of formalin. The highest dose of gabapentin (100 microgram) shifted the EC(50) values of formalin for both flinches and weighted pain scores to the right by 2.5-fold, suggesting that formalin was perceived to be significantly less noxious. Gabapentin also decreased phase 2 behaviors when administered after formalin but was only one third as potent. Unlike its inhibition of formalin-evoked nociceptive behaviors, the effect of gabapentin on the expression of Fos-like immunoreactivity in the spinal cord was highly dependent on the concentration of formalin. Intrathecal pretreatment with 100 microgram of gabapentin did not decrease the numbers of Fos-LI neurons evoked by 0.5% formalin, yet this dose decreased the numbers of Fos-LI neurons in laminae I-II and VII-X of rats that received 1.25% formalin and uniformly decreased by 50% the numbers of Fos-LI neurons in all laminae of rats that received 2.5% formalin. These latter findings suggest that gabapentin neither nonselectively decreases the excitability of spinal cord neurons nor uniformly inhibits the release of all neurotransmitters from primary afferent terminals. Rather, its effects may be preferential for those neurotransmitters released by higher, more noxious concentrations of formalin and for conditions in which there is a greater induction of central sensitization.

Immunohistochemistry

Injections, Spinal

gamma-Aminobutyric Acid

Analgesics - pharmacology

Amines

Spinal Cord - drug effects

Rats

Male

Rats, Sprague-Dawley

Dose-Response Relationship, Drug

Animals

Drug Interactions

Acetates - administration & dosage

Time Factors

Spinal Cord - pathology

Foot - physiology

Hindlimb - drug effects

Acetates - pharmacology

Cyclohexanecarboxylic Acids

Formaldehyde - toxicity

Neurons - drug effects

Pain Measurement

Nociceptors - drug effects

Details

Title: Subtitle: Intrathecally administered gabapentin inhibits formalin-evoked nociception and the expression of Fos-like immunoreactivity in the spinal cord of the rat
Creators: Megumi Kaneko - Department of Anesthesia, University of Chicago, Chicago, Illinois, USA
Christine Mestre
Edgard H Sánchez
Donna L Hammond
Resource Type: Journal article
Publication Details: The Journal of pharmacology and experimental therapeutics, Vol.292(2), pp.743-751
Publisher: United States
DOI: 10.1016/S0022-3565(24)35347-9
PMID: 10640314
ISSN: 0022-3565
eISSN: 1521-0103
Language: English
Date published: 02/2000
Academic Unit: Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
Record Identifier: 9984007189202771

Metrics

22 Record Views

76 Times Cited - Web of Science