Treatments for neuropathic pain differentially affect delayed matching accuracy by macaques

Effects of amitriptyline and gabapentin

Jerry J. Buccafusco, Alvin V Terry, Almira Ivanova Vazdarjanova, Terrance P. Snutch, Stephen P. Arneric

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Current clinical treatments for neuropathic pain include amitriptyline, a tricyclic antidepressant with mixed pharmacology that is also clinically reported to impair cognitive performance; and gabapentin, a compound that selectively interacts with α2δ-1 calcium channel subunits. Since few assessments of cognitive performance have been made in non-human primates with these marketed treatments, the purpose of this study was to determine their relative abilities to alter working memory as measured in mature macaques in their performance of a delayed matching-to-sample task. Four delay intervals of increasing duration provided increasing impairment in task accuracies during vehicle sessions. Administration of clinically relevant doses of amitriptyline significantly decreased task accuracy at the highest dose tested (3 mg/kg). Administration of gabapentin increased mean task accuracy, though the effect was not statistically significant until intra-subject variability was reduced by selecting the individual best dose for each animal (which averaged 12.8 mg/kg). Most of the effect was obtained during the presentation of long delay trials (18.2% above vehicle). Task improvement was sustained during sessions run 24 h after gabapentin administration. In a series that used a task-relevant distractor to determine gabapentin's effect on attention, drug treatment reversed distractor-impaired accuracy during long delay trials (25.4% above vehicle). The selective improvement in long delay accuracy in both paradigms suggests improvement in encoding or retention components of working memory. It is currently unclear whether the ability of acute administration of gabapentin to modestly improve working memory occurs by a mechanism that could be related to its anti-allodynic mechanism of action.

Original languageEnglish (US)
Pages (from-to)446-453
Number of pages8
JournalPain
Volume148
Issue number3
DOIs
StatePublished - Mar 1 2010

Fingerprint

Amitriptyline
Macaca
Neuralgia
Short-Term Memory
Aptitude
Therapeutics
Tricyclic Antidepressive Agents
Calcium Channels
Primates
gabapentin
Pharmacology
Pharmaceutical Preparations

Keywords

  • Allodynia
  • Antidepressant
  • Attention deficit
  • Monkeys
  • Operant task
  • Working memory

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Treatments for neuropathic pain differentially affect delayed matching accuracy by macaques : Effects of amitriptyline and gabapentin. / Buccafusco, Jerry J.; Terry, Alvin V; Vazdarjanova, Almira Ivanova; Snutch, Terrance P.; Arneric, Stephen P.

In: Pain, Vol. 148, No. 3, 01.03.2010, p. 446-453.

Research output: Contribution to journalArticle

@article{39ce016d23434138be6934fc9c5275ce,
title = "Treatments for neuropathic pain differentially affect delayed matching accuracy by macaques: Effects of amitriptyline and gabapentin",
abstract = "Current clinical treatments for neuropathic pain include amitriptyline, a tricyclic antidepressant with mixed pharmacology that is also clinically reported to impair cognitive performance; and gabapentin, a compound that selectively interacts with α2δ-1 calcium channel subunits. Since few assessments of cognitive performance have been made in non-human primates with these marketed treatments, the purpose of this study was to determine their relative abilities to alter working memory as measured in mature macaques in their performance of a delayed matching-to-sample task. Four delay intervals of increasing duration provided increasing impairment in task accuracies during vehicle sessions. Administration of clinically relevant doses of amitriptyline significantly decreased task accuracy at the highest dose tested (3 mg/kg). Administration of gabapentin increased mean task accuracy, though the effect was not statistically significant until intra-subject variability was reduced by selecting the individual best dose for each animal (which averaged 12.8 mg/kg). Most of the effect was obtained during the presentation of long delay trials (18.2{\%} above vehicle). Task improvement was sustained during sessions run 24 h after gabapentin administration. In a series that used a task-relevant distractor to determine gabapentin's effect on attention, drug treatment reversed distractor-impaired accuracy during long delay trials (25.4{\%} above vehicle). The selective improvement in long delay accuracy in both paradigms suggests improvement in encoding or retention components of working memory. It is currently unclear whether the ability of acute administration of gabapentin to modestly improve working memory occurs by a mechanism that could be related to its anti-allodynic mechanism of action.",
keywords = "Allodynia, Antidepressant, Attention deficit, Monkeys, Operant task, Working memory",
author = "Buccafusco, {Jerry J.} and Terry, {Alvin V} and Vazdarjanova, {Almira Ivanova} and Snutch, {Terrance P.} and Arneric, {Stephen P.}",
year = "2010",
month = "3",
day = "1",
doi = "10.1016/j.pain.2009.12.003",
language = "English (US)",
volume = "148",
pages = "446--453",
journal = "Pain",
issn = "0304-3959",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Treatments for neuropathic pain differentially affect delayed matching accuracy by macaques

T2 - Effects of amitriptyline and gabapentin

AU - Buccafusco, Jerry J.

AU - Terry, Alvin V

AU - Vazdarjanova, Almira Ivanova

AU - Snutch, Terrance P.

AU - Arneric, Stephen P.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Current clinical treatments for neuropathic pain include amitriptyline, a tricyclic antidepressant with mixed pharmacology that is also clinically reported to impair cognitive performance; and gabapentin, a compound that selectively interacts with α2δ-1 calcium channel subunits. Since few assessments of cognitive performance have been made in non-human primates with these marketed treatments, the purpose of this study was to determine their relative abilities to alter working memory as measured in mature macaques in their performance of a delayed matching-to-sample task. Four delay intervals of increasing duration provided increasing impairment in task accuracies during vehicle sessions. Administration of clinically relevant doses of amitriptyline significantly decreased task accuracy at the highest dose tested (3 mg/kg). Administration of gabapentin increased mean task accuracy, though the effect was not statistically significant until intra-subject variability was reduced by selecting the individual best dose for each animal (which averaged 12.8 mg/kg). Most of the effect was obtained during the presentation of long delay trials (18.2% above vehicle). Task improvement was sustained during sessions run 24 h after gabapentin administration. In a series that used a task-relevant distractor to determine gabapentin's effect on attention, drug treatment reversed distractor-impaired accuracy during long delay trials (25.4% above vehicle). The selective improvement in long delay accuracy in both paradigms suggests improvement in encoding or retention components of working memory. It is currently unclear whether the ability of acute administration of gabapentin to modestly improve working memory occurs by a mechanism that could be related to its anti-allodynic mechanism of action.

AB - Current clinical treatments for neuropathic pain include amitriptyline, a tricyclic antidepressant with mixed pharmacology that is also clinically reported to impair cognitive performance; and gabapentin, a compound that selectively interacts with α2δ-1 calcium channel subunits. Since few assessments of cognitive performance have been made in non-human primates with these marketed treatments, the purpose of this study was to determine their relative abilities to alter working memory as measured in mature macaques in their performance of a delayed matching-to-sample task. Four delay intervals of increasing duration provided increasing impairment in task accuracies during vehicle sessions. Administration of clinically relevant doses of amitriptyline significantly decreased task accuracy at the highest dose tested (3 mg/kg). Administration of gabapentin increased mean task accuracy, though the effect was not statistically significant until intra-subject variability was reduced by selecting the individual best dose for each animal (which averaged 12.8 mg/kg). Most of the effect was obtained during the presentation of long delay trials (18.2% above vehicle). Task improvement was sustained during sessions run 24 h after gabapentin administration. In a series that used a task-relevant distractor to determine gabapentin's effect on attention, drug treatment reversed distractor-impaired accuracy during long delay trials (25.4% above vehicle). The selective improvement in long delay accuracy in both paradigms suggests improvement in encoding or retention components of working memory. It is currently unclear whether the ability of acute administration of gabapentin to modestly improve working memory occurs by a mechanism that could be related to its anti-allodynic mechanism of action.

KW - Allodynia

KW - Antidepressant

KW - Attention deficit

KW - Monkeys

KW - Operant task

KW - Working memory

UR - http://www.scopus.com/inward/record.url?scp=76349102790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76349102790&partnerID=8YFLogxK

U2 - 10.1016/j.pain.2009.12.003

DO - 10.1016/j.pain.2009.12.003

M3 - Article

VL - 148

SP - 446

EP - 453

JO - Pain

JF - Pain

SN - 0304-3959

IS - 3

ER -