The Synergistic Effect of Intrathecally Administered Dexmedetomidine and Ketorolac on Mechanical Allodynia in Rats with Spinal Nerve Ligation

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Kosin Med J. 2016;31(2):113-121

Publication date (electronic) : 2016 January 20

doi : https://doi.org/10.7180/kmj.2016.31.2.113

Yong Kwan Cheong ^,, Yeon Dong Kim , Ju Hwan Lee , Hyang Do Ham , Seung Won Choi , Seon Jeong Park

Department of Anesthesiology and Pain Medicine, School of Medicine, Wonkwang University, Iksan-si, Jeollabuk-do, Korea

Corresponding Author: Yong Kwan Cheong, Department of Anesthesiology and Pain Medicine, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan-si, Jeollabuk-do 54538, Korea Tel: +82-63-859-1565 Fax: +82-63-857-5472 E-mail: ykfolder@wku.ac.kr

Received 2016 April 28; 2016 May 27; Accepted 2016 June 01.

Abstract

Objectives

This research was carried out to identify the synergistic effect of dexmedetomidine and ketorolac on neuropathic pain alleviation.

Methods

The anti-allodynic effect of intrathecal dexmedetomidine and ketorolac was investigated in rats after L5 spinal nerve ligation (SNL). Mechanical allodynia was assessed using Von Frey filaments. Every day for 3 consecutive days, beginning on the 10th day after SNL, behavioral tests were carried out at 1, 2, and 4 hr after drug injection.

Results

Significant increases in ipsilateral paw withdrawal thresholds (PWTs) were observed 1, 2, and 4 hr after drug injection in the groups of rats which received intrathecal injection of either dexmedetomidine (group D) or ketorolac (group K), compared to group S (P< 0.05). And group DK, which received simultaneous intrathecal injection of both dexmedetomidine and ketorolac, showed statistically significantly higher ipsilateral PWTs than groups D and K, which received only one of them (P< 0.05).

Conclusions

The results of this research demonstrated the anti-allodynic effect of dexmedetomidine and ketorolac on neuropathic pain induced by SNL in rats. They also suggest that synergistic analgesia can be induced by the simultaneous injection of dexmedetomidine and ketorolac, and that combination therapy is an effective approach to treating chronic neuropathic pain syndrome.

Keywords: Allodynia; Dexmedetomidine; Ketorolac; Neuropathic pain; Spinal nerve ligation

Fig. 1.

The alleviating effect of intrathecal dexmedetomidine and ketorolac on mechanical allodynia in spinal nerve ligation rats. All the rats underwent SNL. Group S (n = 5) received intrathecal injection of normal saline, while groups D (n = 5) and K (n = 5) received intrathecal injection of dexmedetomidine and ketorolac, respectively. Group DK (n = 5) received simultaneous intrathecal injection of both dexmedetomidine and ketorolac. At 1, 2, and 4 hr after drug injection, on 3 consecutive days beginning on the 10th day after SNL, statistically significant increases in ipsilateral paw withdrawal thresholds were shown by groups D and K compared to group S (P< 0.05); and by Group DK compared to groups D and K (P< 0.05). ∗P< 0.05 compared to Group S, † P< 0.05 compared to Group D. ‡P< 0.05 compared to Group K.

Fig. 2.

Increases in ipsilateral paw withdrawal thresholds in spinal nerve ligation rats caused by intrathecal dexmedetomidine and ketorola. Regarding % pre-SNL in ipsilateral paw, significantly higher PWTs were shown by groups D and K compared to group S at 1, 2, and 4hr after drug injection, on 3 consecutive days beginning on the 10th day after SNL (P< 0.05); and by group DK compared to groups D and K (P< 0.05). ∗P< 0.05 compared to Group S, †P< 0.05 compared to Group D. ‡P< 0.05 compared to Group K.

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