Co-Administered Low Doses Of Ibuprofen And Dexamethasone Produce Synergistic Antinociceptive Effects On Neuropathic Mechanical Allodynia In Rats

Min K Park; Song H Kang; Jo Y Son; Min K Lee; Jin S Ju; Yong C Bae; Dong K Ahn

doi:10.2147/JPR.S222095

Co-Administered Low Doses Of Ibuprofen And Dexamethasone Produce Synergistic Antinociceptive Effects On Neuropathic Mechanical Allodynia In Rats

J Pain Res. 2019 Oct 30:12:2959-2968. doi: 10.2147/JPR.S222095. eCollection 2019.

Authors

Min K Park^#¹, Song H Kang^#², Jo Y Son², Min K Lee³, Jin S Ju², Yong C Bae⁴, Dong K Ahn²

Affiliations

¹ Department of Dental Hygiene, Kyungwon University, Gumi, Korea.
² Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
³ Department of Dental Hygiene, Dong-Eui University, Busan, Korea.
⁴ Department of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu, Korea.

^# Contributed equally.

Abstract

Background: The traditional analgesics used to treat neuropathic pain such as anticonvulsants, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs) lack efficacy and/or carry unpleasant side effects. The present study aimed to investigate the synergistic antinociceptive effects of co-administered low doses of ibuprofen and dexamethasone in rats with trigeminal neuropathic pain.

Materials and methods: A Sprague-Dawley rat model for trigeminal neuropathic pain was produced using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia and replaced with a miniature dental implant to induce injury to the inferior alveolar nerve.

Results: Monotherapy with intraperitoneal injection of high-dose ibuprofen (30 mg/kg) or dexamethasone (10 mg/kg) but not low-dose ibuprofen (1, 5, 10 mg/kg) or dexamethasone (0.01, 1 mg/kg) attenuated the neuropathic mechanical allodynia in the rats with inferior alveolar nerve injury. We examined the synergistic antinociceptive effects of co-administered ibuprofen (5 mg/kg) and dexamethasone (0.01, 0.1, 1 mg/kg). The early co-administration of ibuprofen (5 mg/kg) with dexamethasone (0.1, 1 mg/kg) on postoperative days (POD) 1-3 significantly inhibited mechanical allodynia before the pain had been established. We also observed the synergistic antinociceptive effects of the same doses the combined treatment on mechanical allodynia on POD 7-9, when the pain had already been established. The attenuation of c-fos immuno-positive cells in the ipsilateral trigeminal subnucleus caudalis after the intraperitoneal co-administration of ibuprofen (5 mg/kg) with dexamethasone (1 mg/kg) confirmed these synergistic antinociceptive effects. Moreover, the magnitude of the effects of this co-administration was comparable with that of gabapentin both before and after the pain had been established.

Conclusion: These results suggest that a combination of ibuprofen and dexamethasone at low doses is an alternative therapeutic strategy for neuropathic pain and provide a rationale for the use of such drug combinations in patients who are unable to tolerate high-dose monotherapy.

Keywords: dexamethasone; ibuprofen; neuropathic pain; synergistic antinociceptive effects; trigeminal.