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Gabapentin prevents delayed and long-lasting hyperalgesia induced by fentanyl in rats.
Anesthesiology. 2008 Mar; 108(3):484-94.A

Abstract

BACKGROUND

Opioid-induced hyperalgesia can develop rapidly after opioid exposure. Neuropathic pain and opioid-induced hyperalgesia share common pathophysiologic mechanisms. Gabapentin is effective for the management of neuropathic pain and may therefore prevent opioid-induced hyperalgesia. This study tested the effectiveness of gabapentin for prevention of long-lasting hyperalgesia induced by acute systemic fentanyl in uninjured rats. Involvement of the alpha2delta auxiliary subunits of voltage-gated calcium channels in the prevention of opioid-induced hyperalgesia by gabapentin also was assessed.

METHODS

Hyperalgesia was induced in male Sprague-Dawley rats with subcutaneous fentanyl (four injections, 20, 60, or 100 microg/kg per injection at 15-min intervals). Intraperitoneal (30, 75, 150, or 300 mg/kg) or intrathecal (300 microg) gabapentin was administered 30 min before or 300 min after (intraperitoneal 150 mg/kg) the first fentanyl injection. Sensitivity to nociceptive stimuli (paw-pressure test) was assessed on the day of the experiment and for several days after injections. The effects combining gabapentin with intrathecal ruthenium red (20 ng) also were assessed.

RESULTS

Fentanyl administration was followed by an early increase (analgesia) and by a later and sustained decrease (hyperalgesia) in nociceptive thresholds. Gabapentin did not significantly modify the early analgesic component but dose-dependently prevented the delayed decrease in nociceptive threshold. Ruthenium red partially, but significantly, opposed the prevention of opioid-induced hyperalgesia by gabapentin.

CONCLUSIONS

Intraperitoneal and intrathecal gabapentin prevents the development of hyperalgesia induced by acute systemic exposure to opioids. This prevention may result, at least in part, from binding of gabapentin to the alpha2delta auxiliary subunits of voltage-gated calcium channels.

Authors+Show Affiliations

Université Paris-Sud, Assistance Publique-Hôpitaux de Paris, Département d'Anesthésie-Réanimation, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

18292686

Citation

Van Elstraete, Alain C., et al. "Gabapentin Prevents Delayed and Long-lasting Hyperalgesia Induced By Fentanyl in Rats." Anesthesiology, vol. 108, no. 3, 2008, pp. 484-94.
Van Elstraete AC, Sitbon P, Mazoit JX, et al. Gabapentin prevents delayed and long-lasting hyperalgesia induced by fentanyl in rats. Anesthesiology. 2008;108(3):484-94.
Van Elstraete, A. C., Sitbon, P., Mazoit, J. X., & Benhamou, D. (2008). Gabapentin prevents delayed and long-lasting hyperalgesia induced by fentanyl in rats. Anesthesiology, 108(3), 484-94. https://doi.org/10.1097/ALN.0b013e318164cf85
Van Elstraete AC, et al. Gabapentin Prevents Delayed and Long-lasting Hyperalgesia Induced By Fentanyl in Rats. Anesthesiology. 2008;108(3):484-94. PubMed PMID: 18292686.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gabapentin prevents delayed and long-lasting hyperalgesia induced by fentanyl in rats. AU - Van Elstraete,Alain C, AU - Sitbon,Philippe, AU - Mazoit,Jean-Xavier, AU - Benhamou,Dan, PY - 2008/2/23/pubmed PY - 2008/3/13/medline PY - 2008/2/23/entrez SP - 484 EP - 94 JF - Anesthesiology JO - Anesthesiology VL - 108 IS - 3 N2 - BACKGROUND: Opioid-induced hyperalgesia can develop rapidly after opioid exposure. Neuropathic pain and opioid-induced hyperalgesia share common pathophysiologic mechanisms. Gabapentin is effective for the management of neuropathic pain and may therefore prevent opioid-induced hyperalgesia. This study tested the effectiveness of gabapentin for prevention of long-lasting hyperalgesia induced by acute systemic fentanyl in uninjured rats. Involvement of the alpha2delta auxiliary subunits of voltage-gated calcium channels in the prevention of opioid-induced hyperalgesia by gabapentin also was assessed. METHODS: Hyperalgesia was induced in male Sprague-Dawley rats with subcutaneous fentanyl (four injections, 20, 60, or 100 microg/kg per injection at 15-min intervals). Intraperitoneal (30, 75, 150, or 300 mg/kg) or intrathecal (300 microg) gabapentin was administered 30 min before or 300 min after (intraperitoneal 150 mg/kg) the first fentanyl injection. Sensitivity to nociceptive stimuli (paw-pressure test) was assessed on the day of the experiment and for several days after injections. The effects combining gabapentin with intrathecal ruthenium red (20 ng) also were assessed. RESULTS: Fentanyl administration was followed by an early increase (analgesia) and by a later and sustained decrease (hyperalgesia) in nociceptive thresholds. Gabapentin did not significantly modify the early analgesic component but dose-dependently prevented the delayed decrease in nociceptive threshold. Ruthenium red partially, but significantly, opposed the prevention of opioid-induced hyperalgesia by gabapentin. CONCLUSIONS: Intraperitoneal and intrathecal gabapentin prevents the development of hyperalgesia induced by acute systemic exposure to opioids. This prevention may result, at least in part, from binding of gabapentin to the alpha2delta auxiliary subunits of voltage-gated calcium channels. SN - 1528-1175 UR - https://www.unboundmedicine.com/medline/citation/18292686/Gabapentin_prevents_delayed_and_long_lasting_hyperalgesia_induced_by_fentanyl_in_rats_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/ALN.0b013e318164cf85 DB - PRIME DP - Unbound Medicine ER -