Tags

Type your tag names separated by a space and hit enter

Low dose of donepezil improves gabapentin analgesia in the rat spared nerve injury model of neuropathic pain: single and multiple dosing studies.
J Neural Transm (Vienna). 2010 Dec; 117(12):1377-85.JN

Abstract

The use of cholinergic drugs, either alone or in combination with other drugs, has been suggested as an approach to improve treatment outcome for patients suffering from neuropathic pain. The present study was undertaken in the rat spared nerve injury model of neuropathic pain to evaluate the effect of the cholinesterase inhibitor donepezil when administered (1) alone and (2) as low-dose in combination with the first-line recommendation gabapentin. The co-administration studies were performed following single and multiple dosing. Single, parenteral dosing of donepezil (1, 1.5 and 3 mg/kg s.c.) produced a dose-dependent reversal of the neuropathic pain behaviour. Co-administration of a sub-effective dose of donepezil (0.5 mg/kg s.c.) and low doses of gabapentin (10 and 30 mg/kg s.c.) resulted in a three- to fourfold increase of the analgesic effect, in comparison with gabapentin administered alone. Following multiple, oral dosing, gabapentin (25 mg/kg p.o.) was administered once daily over 20 days. Addition of donepezil (1.5 mg/kg p.o.) from day 11 to day 20 resulted in improved analgesia during the period of combination therapy, in comparison with the gabapentin monotherapy period. Furthermore, the treatment effects were stable in both the mono- and the combination therapy period, indicating that tolerance development does not occur within the studied time frame. In conclusion, the results from this preclinical study support the use of donepezil as adjunctive to gabapentin to improve the therapeutic outcome in the management of neuropathic pain.

Authors+Show Affiliations

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. af@farma.ku.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article

Language

eng

PubMed ID

20890617

Citation

Folkesson, Anna, et al. "Low Dose of Donepezil Improves Gabapentin Analgesia in the Rat Spared Nerve Injury Model of Neuropathic Pain: Single and Multiple Dosing Studies." Journal of Neural Transmission (Vienna, Austria : 1996), vol. 117, no. 12, 2010, pp. 1377-85.
Folkesson A, Honoré PH, Andersen LM, et al. Low dose of donepezil improves gabapentin analgesia in the rat spared nerve injury model of neuropathic pain: single and multiple dosing studies. J Neural Transm (Vienna). 2010;117(12):1377-85.
Folkesson, A., Honoré, P. H., Andersen, L. M., Kristensen, P., & Bjerrum, O. J. (2010). Low dose of donepezil improves gabapentin analgesia in the rat spared nerve injury model of neuropathic pain: single and multiple dosing studies. Journal of Neural Transmission (Vienna, Austria : 1996), 117(12), 1377-85. https://doi.org/10.1007/s00702-010-0494-4
Folkesson A, et al. Low Dose of Donepezil Improves Gabapentin Analgesia in the Rat Spared Nerve Injury Model of Neuropathic Pain: Single and Multiple Dosing Studies. J Neural Transm (Vienna). 2010;117(12):1377-85. PubMed PMID: 20890617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low dose of donepezil improves gabapentin analgesia in the rat spared nerve injury model of neuropathic pain: single and multiple dosing studies. AU - Folkesson,Anna, AU - Honoré,Per Hartvig, AU - Andersen,Lene Munkholm, AU - Kristensen,Pernille, AU - Bjerrum,Ole J, Y1 - 2010/10/02/ PY - 2010/05/04/received PY - 2010/09/21/accepted PY - 2010/10/5/entrez PY - 2010/10/5/pubmed PY - 2011/11/15/medline SP - 1377 EP - 85 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 117 IS - 12 N2 - The use of cholinergic drugs, either alone or in combination with other drugs, has been suggested as an approach to improve treatment outcome for patients suffering from neuropathic pain. The present study was undertaken in the rat spared nerve injury model of neuropathic pain to evaluate the effect of the cholinesterase inhibitor donepezil when administered (1) alone and (2) as low-dose in combination with the first-line recommendation gabapentin. The co-administration studies were performed following single and multiple dosing. Single, parenteral dosing of donepezil (1, 1.5 and 3 mg/kg s.c.) produced a dose-dependent reversal of the neuropathic pain behaviour. Co-administration of a sub-effective dose of donepezil (0.5 mg/kg s.c.) and low doses of gabapentin (10 and 30 mg/kg s.c.) resulted in a three- to fourfold increase of the analgesic effect, in comparison with gabapentin administered alone. Following multiple, oral dosing, gabapentin (25 mg/kg p.o.) was administered once daily over 20 days. Addition of donepezil (1.5 mg/kg p.o.) from day 11 to day 20 resulted in improved analgesia during the period of combination therapy, in comparison with the gabapentin monotherapy period. Furthermore, the treatment effects were stable in both the mono- and the combination therapy period, indicating that tolerance development does not occur within the studied time frame. In conclusion, the results from this preclinical study support the use of donepezil as adjunctive to gabapentin to improve the therapeutic outcome in the management of neuropathic pain. SN - 1435-1463 UR - https://www.unboundmedicine.com/medline/citation/20890617/Low_dose_of_donepezil_improves_gabapentin_analgesia_in_the_rat_spared_nerve_injury_model_of_neuropathic_pain:_single_and_multiple_dosing_studies_ L2 - https://doi.org/10.1007/s00702-010-0494-4 DB - PRIME DP - Unbound Medicine ER -