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Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat

Rheumatoid arthritis (RA) is a chronic inflammatory condition characterised by frequent reports of pain. Ifenprodil, a selective N-methyl-D-aspartate receptor-2B (NMDAR-2B) antagonist, has demonstrated a significant anti-nociceptive effect in chronic pain models. This study aimed to investigate the...

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Main Author: Noh, Ain’ Sabreena Mohd
Format: Thesis
Language:English
Published: 2024
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R Medicine
R735-854 Medical education. Medical schools. Research
RC Internal medicine
Online Access:http://eprints.usm.my/61453/1/AIN%27%20SABREENA%20MOHD%20NOH%20-%20THESIS%20P-UD000622-E.pdf
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spelling my.usm.eprints.61453 http://eprints.usm.my/61453/ Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat Noh, Ain’ Sabreena Mohd R Medicine R735-854 Medical education. Medical schools. Research RC Internal medicine Rheumatoid arthritis (RA) is a chronic inflammatory condition characterised by frequent reports of pain. Ifenprodil, a selective N-methyl-D-aspartate receptor-2B (NMDAR-2B) antagonist, has demonstrated a significant anti-nociceptive effect in chronic pain models. This study aimed to investigate the effect of Ifenprodil as a selective NMDAR-2B antagonist on pain behaviour, inflammation, and nociceptive responses in the spinal cord of CFA-induced polyarthritis, as well as its possible side effect on memory function. Arthritic rats received intrathecal treatment of either Ifenprodil (0.5 or 1.0 μg/μL) or Sodium Diclofenac (6 μg) (positive control) whereas arthritic (A) and non-arthritic (C) control groups were administered with 0.9% normal saline for 7 days (day-16 to -22 post-arthritic induction). Ankle joint diameter and circumference, pain behaviour assessments including von-Frey and hot-plate tests, mobility scoring, and memory test were conducted on day-0 (baseline), day-15 (pre-intervention) and day-23 (post-intervention). Histopathological examination was performed on the ipsilateral ankle joint while the lumbar region of the spinal cord (L4-L5) was collected for ELISA, immunohistochemistry and RT-qPCR analyses. The group receiving Ifenprodil (0.5 μg/μL) showed a non-significant trend of increased body weight with no change in total food intake, attenuation of thermal hyperalgesia, tactile allodynia and improved mobility and significant improvement in the morphology of the ipsilateral hind paws and ankle joints when compared to the arthritic rats receiving Ifenprodil at 1.0 μg/μL. Meanwhile, Ifenprodil has significantly decreased the level of NMDAR-2B, substance P, BDNF and TNF-α proteins with attenuation on the total and phosphorylated NMDAR-2B, BDNF, activated microglia (Iba-1) and P2X4 receptor (P2X4R) mRNA and proteins expression in the polyarthritis rats. Furthermore, pro-apoptotic caspase-3, caspase-8, PKB, and PI3Kcb markers were decreased with no change in the anti-apoptotic Bcl-2 level in the spinal cord compared to the arthritis control group. A significant improvement in the memory discriminative index observed in the polyarthritis rats, especially at the concentration of 0.5 µg/µL implies a beneficial influence of Ifenprodil on memory enhancement. Thus, Ifenprodil, particularly at 0.5 μg/μL demonstrated significant anti-nociceptive and anti-inflammatory effects comparable to those of Sodium Diclofenac. These results underscore the potential involvement of NMDAR-2B activation in the pathogenesis of chronic arthritic pain. 2024-09 Thesis NonPeerReviewed application/pdf en http://eprints.usm.my/61453/1/AIN%27%20SABREENA%20MOHD%20NOH%20-%20THESIS%20P-UD000622-E.pdf Noh, Ain’ Sabreena Mohd (2024) Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat. PhD thesis, Universiti Sains Malaysia.
institution Universiti Sains Malaysia
building Hamzah Sendut Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Sains Malaysia
content_source USM Institutional Repository
url_provider http://eprints.usm.my/
language English
topic R Medicine
R735-854 Medical education. Medical schools. Research
RC Internal medicine
spellingShingle R Medicine
R735-854 Medical education. Medical schools. Research
RC Internal medicine
Noh, Ain’ Sabreena Mohd
Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat
description Rheumatoid arthritis (RA) is a chronic inflammatory condition characterised by frequent reports of pain. Ifenprodil, a selective N-methyl-D-aspartate receptor-2B (NMDAR-2B) antagonist, has demonstrated a significant anti-nociceptive effect in chronic pain models. This study aimed to investigate the effect of Ifenprodil as a selective NMDAR-2B antagonist on pain behaviour, inflammation, and nociceptive responses in the spinal cord of CFA-induced polyarthritis, as well as its possible side effect on memory function. Arthritic rats received intrathecal treatment of either Ifenprodil (0.5 or 1.0 μg/μL) or Sodium Diclofenac (6 μg) (positive control) whereas arthritic (A) and non-arthritic (C) control groups were administered with 0.9% normal saline for 7 days (day-16 to -22 post-arthritic induction). Ankle joint diameter and circumference, pain behaviour assessments including von-Frey and hot-plate tests, mobility scoring, and memory test were conducted on day-0 (baseline), day-15 (pre-intervention) and day-23 (post-intervention). Histopathological examination was performed on the ipsilateral ankle joint while the lumbar region of the spinal cord (L4-L5) was collected for ELISA, immunohistochemistry and RT-qPCR analyses. The group receiving Ifenprodil (0.5 μg/μL) showed a non-significant trend of increased body weight with no change in total food intake, attenuation of thermal hyperalgesia, tactile allodynia and improved mobility and significant improvement in the morphology of the ipsilateral hind paws and ankle joints when compared to the arthritic rats receiving Ifenprodil at 1.0 μg/μL. Meanwhile, Ifenprodil has significantly decreased the level of NMDAR-2B, substance P, BDNF and TNF-α proteins with attenuation on the total and phosphorylated NMDAR-2B, BDNF, activated microglia (Iba-1) and P2X4 receptor (P2X4R) mRNA and proteins expression in the polyarthritis rats. Furthermore, pro-apoptotic caspase-3, caspase-8, PKB, and PI3Kcb markers were decreased with no change in the anti-apoptotic Bcl-2 level in the spinal cord compared to the arthritis control group. A significant improvement in the memory discriminative index observed in the polyarthritis rats, especially at the concentration of 0.5 µg/µL implies a beneficial influence of Ifenprodil on memory enhancement. Thus, Ifenprodil, particularly at 0.5 μg/μL demonstrated significant anti-nociceptive and anti-inflammatory effects comparable to those of Sodium Diclofenac. These results underscore the potential involvement of NMDAR-2B activation in the pathogenesis of chronic arthritic pain.
format Thesis
author Noh, Ain’ Sabreena Mohd
author_facet Noh, Ain’ Sabreena Mohd
author_sort Noh, Ain’ Sabreena Mohd
title Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat
title_short Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat
title_full Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat
title_fullStr Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat
title_full_unstemmed Effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat
title_sort effects of ifenprodil treatment on pain behaviour, inflammation, and nociceptive responses in the spinal cord of complete freund’s adjuvant-induced chronic polyarthritis rat
publishDate 2024
url http://eprints.usm.my/61453/1/AIN%27%20SABREENA%20MOHD%20NOH%20-%20THESIS%20P-UD000622-E.pdf
http://eprints.usm.my/61453/
_version_ 1823273892434673664
score 13.244413

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