Effects of intrathecally administered interferon α on chronic constriction injury model rats' mechanical pain threshold and G protein expression in the spinal cord

Folia Neuropathol. 2023;61(1):97-104. doi: 10.5114/fn.2023.126016.

Abstract

Introduction: The aim of the study was to explore the analgesic mechanism of effects of intrathecally administered interferon a (IFN-a) on chronic constriction injury (CCI) model rats.

Material and methods: 24 rats were divided into 6 groups, with 4 rats in each group, including the negative control group (Group N, no operation or treatment), the sham operation group (Group S, only the left sciatic nerve of the rats was exposed without ligation, 0.9% NaCl was intrathecally administered), and four experimental groups (CCI model was established first and then different drugs were intrathecally administered respectively), including 0.9% NaCl (Group C), IFN-a (Group CI), morphine (Group CM), and IFN-a combined with morphine (Group CIM). The mRNA levels of G proteins in both the spinal cord and dorsal root ganglia (DRG), as well as the content of amino acid and chemokine (C-X-C motif) ligand 6 (CXCL-6) in the cerebrospinal fluid were measured and analysed in each group.

Results: Intrathecal administration of IFN-a increased the mechanical pain threshold in CCI rats (33.32 ±1.36 vs. 21.08 ±1.59, p < 0.001), achieving the effect comparable to that of morphine (33.32 ±1.36 vs. 32.44 ±3.18, p > 0.05), increased the mRNA expression level of Gi protein (0.62 ±0.04 vs. 0.49 ±0.05, p = 0.006), and decreased the mRNA expression level of Gs protein in the spinal cord (1.80 ±0.16 vs. 2.06 ±0.15, p = 0.035) and DRG (2.11 ±0.10 vs. 2.79 ±0.13, p < 0.001). The intrathecal administration of both IFN-a and morphine can reduce the glutamate content in the cerebrospinal fluid (261.55 ±38.12 vs. 347.70 ±40.69, p = 0.012), but without any statistically significant difference in the content of CXCL-6 across all groups ( p > 0.05).

Conclusions: Intrathecal injection of IFN-a improved the mechanical pain threshold in CCI rats, so we inferred that intrathecal administration of IFN-a had analgesic effects on neuropathic pain, possibly related to the activation of G-proteincoupled µ receptors in the spinal cord and the inhibition of glutamate release.

Keywords: CCI model; G protein; analgesia; intrathecal administration; rats; interferon a.

MeSH terms

  • Animals
  • Constriction
  • GTP-Binding Proteins / metabolism
  • GTP-Binding Proteins / pharmacology
  • Interferon-alpha* / metabolism
  • Interferon-alpha* / pharmacology
  • Morphine Derivatives / metabolism
  • Morphine Derivatives / pharmacology
  • Pain Threshold*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Saline Solution / metabolism
  • Saline Solution / pharmacology
  • Spinal Cord / metabolism

Substances

  • Interferon-alpha
  • Saline Solution
  • GTP-Binding Proteins
  • RNA, Messenger
  • Morphine Derivatives