Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Oct;65(4):331-6.
doi: 10.4097/kjae.2013.65.4.331. Epub 2013 Oct 24.

Synergistic anti-allodynic effect between intraperitoneal thalidomide and morphine on rat spinal nerve ligation-induced neuropathic pain

Hyung Gon Lee  1 , Woong Mo Kim, Myung Ha Yoon, A Reum Park, Jeong-Il Choi
Affiliations

Synergistic anti-allodynic effect between intraperitoneal thalidomide and morphine on rat spinal nerve ligation-induced neuropathic pain

Hyung Gon Lee et al. Korean J Anesthesiol. 2013 Oct.

Abstract

Background: Thalidomide has been recognized as having an anti-allodynic effect against neuropathic pain induced by spinal nerve ligation. Its clinical beneficial effects are mainly derived from its immune-modulating property, which is known to influence the analgesic action of morphine. The possible characteristics of systemic interactions between thalidomide and morphine in the context of spinal nerve ligation-induced neuropathic pain were examined in rats.

Methods: Neuropathic pain was induced by ligation of the L5/6 spinal nerves in male Sprague-Dawley rats and mechanical allodynia was assessed using von Frey filaments. The ED50 was calculated for thalidomide and for morphine, and the mixture of both drugs was intraperitoneally administered at different doses of ED50 of each drug (1/8, 1/4, 1/2, 1/1 of ED50) to obtain the experimental ED50 value for the combination of thalidomide and morphine. Isobolographic analysis was used to evaluate the characteristics of drug interactions between morphine and thalidomide.

Results: The ED50 of thalidomide was three-fold higher than that of morphine. The experimental ED50 value of the mixture of thalidomide and morphine was significantly lower than the calculated theoretical ED50 value. Isobolographic analysis revealed a synergistic interaction for anti-allodynic effect after intraperitoneal delivery of the thalidomide-morphine mixture.

Conclusions: These results suggest that thalidomide acts synergistically with morphine to produce an anti-allodynic effect in neuropathic pain induced by spinal nerve ligation in rats. Thus, the combination of thalidomide with morphine may be one of the useful strategies in the management of neuropathic pain.

Keywords: Analgesics; Drug synergism; Intraperitoneal injection; Morphine; Thalidomide.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Change in paw withdrawal threshold in spinal nerve-ligated rats. After the surgery, PWT of ipsilateral side of spinal nerve ligation is significantly decreased compared to contralateral side. *P < 0.01 vs. contralateral.
Fig. 2
Fig. 2
Paw withdrawal threshold was significantly increased by the administration of mixture of thalidomide and morphine compared to baseline. The maximal possible effect (MPE, %) was increased as the proportion of combination dose to ED50 values for each drug was increased. *P < 0.01 vs. baseline, †P < 0.01 vs. 1/8 (proportion of mixture to ED50).
Fig. 3
Fig. 3
Isobologram for the interaction between thalidomide and morphine is depicted. The ED50 values for each drug are plotted on the x- and y-axes. Dark circle, mean; bar, SEM. The straight lines connecting ED50 values indicate the combinations of drugs that have the same effect as the ED50 value of individual drugs in the case of an additive interaction. The points on this line indicate the theoretical additive ED50 values (A). The horizontal and vertical bars represent SEM. The experimental ED50 value (B) was significantly different from the theoretical ED50, indicating a synergistic interaction. *P < 0.01 vs. theoretical (A).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical research purposes. Neurology. 2008;70:1630–1635. - PubMed
    1. Wallace JM. Update on pharmacotherapy guidelines for treatment of neuropathic pain. Curr Pain Headache Rep. 2007;11:208–214. - PubMed
    1. Ji RR, Strichartz G. Cell signaling and the genesis of neuropathic pain. Sci STKE. 2004;2004:reE14. - PubMed
    1. Watkins LR, Milligan ED, Maier SF. Spinal cord glia: new players in pain. Pain. 2001;93:201–205. - PubMed
    1. Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends Neurosci. 2001;24:450–455. - PubMed

LinkOut - more resources