Involvement of microglial cells in the antinociceptive effects of metamizol in a mouse model of neuropathic pain.

Abstract

Metamizol (also known as dipyrone or sulpyrine) is one of the non-opioid analgesics commonly used in clinical practice in the treatment of somatic and visceral pain. Here, our results give evidence that repeated twice daily intraperitoneal metamizol administration during 7 days diminished development of neuropathic pain symptoms in a mouse model of neuropathic pain. We observed that metamizol inhibited the activation of spinal microglia in neuropathic mice. Moreover, our findings provide evidence that pronociceptive (IL-1β, XCL1, and CCL2), but not antinociceptive (IL-1α, IL-1RA, and IL-18BP), factors play an important role in metamizol-induced antinociception. We observed that metamizol influences the spinal levels of the nociceptin receptor (NOP) but does not alter the expression of other members of the opioid receptor family (mu (MOP), delta (DOP) and kappa (KOP)), or other important nociception receptors (transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1)). Metamizol administration did not affect the levels of the opioid prohormones (proopiomelanocortin (POMC), proenkephalin (PENK), prodynorphin (PDYN), and pronociceptin (PNOC)). However, we observed an enhanced antinociceptive effect of oxycodone, but not buprenorphine, after metamizol treatment. In conclusion, we found that metamizol-induced analgesia in neuropathy is associated with silencing microglia activation and, consequently, with a reduction in pronociceptive cytokines. These results provide evidence that metamizol may join the modest arsenal of effective remedies for neuropathic pain and may constitute part of a multimodal pain therapy.

• Authors: R Zajaczkowska, K Popiolek-Barczyk, D Pilat, E Rojewska, W Makuch, J Wordliczek, J Mika
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 175 Pg. 77-88 (12 2018) ISSN: 1873-5177 [Electronic] United States
• PMID: 30267794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• RNA, Messenger
• Dipyrone
• Complement C1q

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Complement C1q (metabolism)
• Cytokines (genetics, metabolism)
• Dipyrone (pharmacology, therapeutic use)
• Disease Models, Animal
• Male
• Mice
• Microglia (drug effects, pathology)
• Neuralgia (drug therapy)
• RNA, Messenger (metabolism)
• Spinal Cord (metabolism)