The Effect of Intrathecal Injection of Dextromethorphan on the Experimental Model of Neuropathic Pain


Achmad Fahmi ORCID 1 , * , Yunus Kuntawi Aji ORCID 1 , Dirga Rachmad Aprianto ORCID 1 , Akbar Wido 1 , Asadullah Asadullah ORCID 1 , Nurkholis Roufi 2 , Danti Nur Indiastuti 3 , Heri Subianto 1 , Agus Turchan 1

1 Neurosurgery Department, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia

2 Wahidin Sudirohusodo General Hospital, Mojokerto, Indonesia

3 Department of Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

How to Cite: Fahmi A, Aji Y K, Aprianto D R, Wido A, Asadullah A, et al. The Effect of Intrathecal Injection of Dextromethorphan on the Experimental Model of Neuropathic Pain, Anesth Pain Med.2021 In Press(In Press): e114318. doi: 10.5812/aapm.114318.


Anesthesiology and Pain Medicine: In Press (In Press); e114318
Published Online: June 05, 2021
Article Type: Research Article
Received: March 06, 2021
Revised: April 27, 2021
Accepted: May 18, 2021
Primary Published scheduled for 11 (3)


Background: Peripheral glucocorticoid receptors (GRs) are altered by peripheral nerve injury and thus may modulate the development of neuropathic pain. Neuroinflammation and N-methyl-D-aspartate receptor (NMDAR)-dependent neural plasticity in the spinal cord are central pathogenic mechanism underlying neuropathic pain.

Objectives: This study examined the effect of the non-competitive NMDAR antagonist dextromethorphan on partial sciatic nerve ligation (PSL)-induced neuropathic pain and spinal expression levels of the glucocorticoid receptor (GR).

Methods: Male mice were randomly divided into a sham group and two groups that receiving PSL followed by intrathecal saline vehicle or dextromethorphan (iDMP). Vehicle or iDMP was administered 8–14 days post-PSL. The hotplate paw withdrawal time was used to measure thermal pain sensitivity. The spinal cord was then sectioned and immunostained for GR.

Results: Thermal hyperalgesia developed similarly in vehicle and iDMP groups prior to injections (P = 0.828 and 0.643) but was completely mitigated during iDMP treatment (P < 0.001). GR Expression was significantly higher in the vehicle group (55.64 ± 4.50) compared to other groups (P < 0.001). iDMP group (9.99 ± 0.66) showed a slightly significant higher compared to the sham group (6.30 ± 1.96) (P = 0.043).

Conclusions: Suppression of PLS-induced thermal hyperalgesia by iDMP is associated with downregulation of GR in spinal cord, suggesting that this analgesic effect is mediated by inhibition of GR-regulated neuroinflammation.


© 2021, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.