Local Magnesium Sulfate Administration Ameliorates Nociception, Peripheral Inflammation, and Spinal Sensitization in a Rat Model of Incisional Pain

Neuroscience. 2024 May 24:547:98-107. doi: 10.1016/j.neuroscience.2024.03.033. Epub 2024 Apr 22.

Abstract

Objective: Postoperative pain remains one of the most common complaints after surgery, and appropriate treatments are limited.

Methods: We therefore investigated the effect of the anti-nociceptive properties of magnesium sulfate (MgSO4), an N-methyl-D-aspartate (NMDA) receptor antagonist, on incision-induced postoperative pain and peripheral and central nervous system inflammation.

Results: We found that local MgSO4 administration dose-dependently increases paw withdrawal latency, indicating reduced peripheral postoperative pain. Furthermore, MgSO4 inhibited the expression of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) and phosphorylation of the NMDA receptor NR1 subunit in injured paw tissue and significantly attenuated microglial and astrocytic activation in the ipsilateral lumbar spinal cord dorsal horn.

Conclusion: Locally administered MgSO4 has potential for development as an adjunctive therapy for preventing central nociceptive sensitization.

Keywords: N-methyl-D-aspartate receptor; magnesium sulfate; postoperative pain.

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / pharmacology
  • Animals
  • Central Nervous System Sensitization / drug effects
  • Central Nervous System Sensitization / physiology
  • Disease Models, Animal
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Interleukin-1beta / metabolism
  • Magnesium Sulfate* / administration & dosage
  • Magnesium Sulfate* / pharmacology
  • Male
  • Microglia / drug effects
  • Microglia / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Nociception* / drug effects
  • Pain, Postoperative* / drug therapy
  • Pain, Postoperative* / metabolism
  • Rats
  • Rats, Sprague-Dawley*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism

Substances

  • Magnesium Sulfate
  • Receptors, N-Methyl-D-Aspartate
  • Analgesics
  • Interleukin-1beta
  • Nitric Oxide Synthase Type II