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Gabapentin augments the antihyperalgesic effects of diclofenac sodium through spinal action in a rat postoperative pain model.
Anesth Analg. 2012 Jul; 115(1):189-93.A&A

Abstract

BACKGROUND

Gabapentin and nonsteroidal antiinflammatory drugs (NSAIDs) attenuate postoperative pain and neuropathic pain in humans. The combination of gabapentin and NSAIDs is effective for postoperative pain and enhances functional recovery after surgery. Intrathecal administration of gabapentin or NSAIDs inhibits hyperalgesia in a rat postoperative pain model. However, there is no information on the effects of intrathecal administration of a combination of gabapentin and NSAIDs. We therefore investigated the effects of intrathecal administration of gabapentin and NSAIDs in a rat model of postoperative pain.

METHODS

Rats were prepared for intrathecal catheters under halothane anesthesia. Two days after catheterization, gabapentin (4, 40, or 400 μg per 20 μL of saline), diclofenac sodium, a nonselective cyclooxygenase inhibitor (2, 20, or 200 μg per 20 μL of 6% glucose), 20 μL saline, 20 μL 6% glucose, and a combination of gabapentin and diclofenac (40 μg gabapentin + 20 μg diclofenac and 4 μg gabapentin + 2 μg diclofenac per 20 μL 6% glucose) were injected intrathecally. We performed a hindpaw incision 30 minutes after injection. Each group consisted of 6 rats. The mechanical threshold was measured to evaluate secondary hyperalgesia using von Frey filaments before intrathecal catheterization and at 2 hours, and 1, 3, 5, and 7 days after paw incision.

RESULTS

Gabapentin 400 μg attenuated mechanical hyperalgesia for 7 days compared with the control group. Diclofenac 200 μg inhibited hyperalgesia for 5 days compared with the control group. The 40 μg gabapentin + 20 μg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 40 μg gabapentin and 20 μg diclofenac, respectively. The 4 μg gabapentin + 2 μg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 2 μg diclofenac. The withdrawal threshold on the contralateral paw did not change compared with the preincision threshold.

CONCLUSION

Intrathecal administration of gabapentin and diclofenac in combination reduced secondary hyperalgesia at doses having no antihyperalgesic effects when given individually. Our results suggest that gabapentin and diclofenac have an important role in postoperative pain reduction at the spinal level, and that gabapentin augments the antihyperalgesic effects of diclofenac through action in the spinal cord.

Authors+Show Affiliations

Department of Anesthesiology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22467888

Citation

Narai, Yasuhiro, et al. "Gabapentin Augments the Antihyperalgesic Effects of Diclofenac Sodium Through Spinal Action in a Rat Postoperative Pain Model." Anesthesia and Analgesia, vol. 115, no. 1, 2012, pp. 189-93.
Narai Y, Imamachi N, Saito Y. Gabapentin augments the antihyperalgesic effects of diclofenac sodium through spinal action in a rat postoperative pain model. Anesth Analg. 2012;115(1):189-93.
Narai, Y., Imamachi, N., & Saito, Y. (2012). Gabapentin augments the antihyperalgesic effects of diclofenac sodium through spinal action in a rat postoperative pain model. Anesthesia and Analgesia, 115(1), 189-93. https://doi.org/10.1213/ANE.0b013e31824e5da3
Narai Y, Imamachi N, Saito Y. Gabapentin Augments the Antihyperalgesic Effects of Diclofenac Sodium Through Spinal Action in a Rat Postoperative Pain Model. Anesth Analg. 2012;115(1):189-93. PubMed PMID: 22467888.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gabapentin augments the antihyperalgesic effects of diclofenac sodium through spinal action in a rat postoperative pain model. AU - Narai,Yasuhiro, AU - Imamachi,Noritaka, AU - Saito,Yoji, Y1 - 2012/03/30/ PY - 2012/4/3/entrez PY - 2012/4/3/pubmed PY - 2012/9/1/medline SP - 189 EP - 93 JF - Anesthesia and analgesia JO - Anesth Analg VL - 115 IS - 1 N2 - BACKGROUND: Gabapentin and nonsteroidal antiinflammatory drugs (NSAIDs) attenuate postoperative pain and neuropathic pain in humans. The combination of gabapentin and NSAIDs is effective for postoperative pain and enhances functional recovery after surgery. Intrathecal administration of gabapentin or NSAIDs inhibits hyperalgesia in a rat postoperative pain model. However, there is no information on the effects of intrathecal administration of a combination of gabapentin and NSAIDs. We therefore investigated the effects of intrathecal administration of gabapentin and NSAIDs in a rat model of postoperative pain. METHODS: Rats were prepared for intrathecal catheters under halothane anesthesia. Two days after catheterization, gabapentin (4, 40, or 400 μg per 20 μL of saline), diclofenac sodium, a nonselective cyclooxygenase inhibitor (2, 20, or 200 μg per 20 μL of 6% glucose), 20 μL saline, 20 μL 6% glucose, and a combination of gabapentin and diclofenac (40 μg gabapentin + 20 μg diclofenac and 4 μg gabapentin + 2 μg diclofenac per 20 μL 6% glucose) were injected intrathecally. We performed a hindpaw incision 30 minutes after injection. Each group consisted of 6 rats. The mechanical threshold was measured to evaluate secondary hyperalgesia using von Frey filaments before intrathecal catheterization and at 2 hours, and 1, 3, 5, and 7 days after paw incision. RESULTS: Gabapentin 400 μg attenuated mechanical hyperalgesia for 7 days compared with the control group. Diclofenac 200 μg inhibited hyperalgesia for 5 days compared with the control group. The 40 μg gabapentin + 20 μg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 40 μg gabapentin and 20 μg diclofenac, respectively. The 4 μg gabapentin + 2 μg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 2 μg diclofenac. The withdrawal threshold on the contralateral paw did not change compared with the preincision threshold. CONCLUSION: Intrathecal administration of gabapentin and diclofenac in combination reduced secondary hyperalgesia at doses having no antihyperalgesic effects when given individually. Our results suggest that gabapentin and diclofenac have an important role in postoperative pain reduction at the spinal level, and that gabapentin augments the antihyperalgesic effects of diclofenac through action in the spinal cord. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/22467888/Gabapentin_augments_the_antihyperalgesic_effects_of_diclofenac_sodium_through_spinal_action_in_a_rat_postoperative_pain_model_ L2 - https://doi.org/10.1213/ANE.0b013e31824e5da3 DB - PRIME DP - Unbound Medicine ER -