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The role of the thalamus in modulating pain

Ab Aziz CB, Ahmad AH

Malays J Med Sci, 2006 Jul;13(2):11-8.
PMID: 22589599 MyJurnal

The thalamus is one of the structures that receives projections from multiple ascending pain pathways. The structure is not merely a relay centre but is involved in processing nociceptive information before transmitting the information to various parts of the cortex. The thalamic nuclei are involved in the sensory discriminative and affective motivational components of pain. Generally each group of nucleus has prominent functions in one component for example ventrobasal complex in sensory discriminative component and intralaminar nuclei in affective-motivational component. The thalamus is also part of a network that projects to the spinal cord dorsal horn and modulates ascending nociceptive information. In the animal models of neuropathic pain, changes in the biochemistry, gene expression, thalamic blood flow and response properties of thalamic neurons have been shown. These studies suggest the important contribution of the thalamus in modulating pain in normal and neuropathic pain condition.
Ifenprodil Reduced Expression of Activated Microglia, BDNF and DREAM Proteins in the Spinal Cord Following Formalin Injection During the Early Stage of Painful Diabetic Neuropathy in Rats

Ismail CAN, Suppian R, Ab Aziz CB, Long I

J Mol Neurosci, 2021 Feb;71(2):379-393.
PMID: 32671697 DOI: 10.1007/s12031-020-01661-1

The pharmacological inhibition of glial activation is one of the new approaches for combating neuropathic pain in which the role of glia in the modulation of neuropathic pain has attracted significant interest and attention. Neuron-glial crosstalk is achieved with N-methyl-D-aspartate-2B receptor (NMDAR-2B) activation. This study aims to determine the effect of ifenprodil, a potent noncompetitive NMDAR-2B antagonist, on activated microglia, brain-derived neurotrophic factors (BDNF) and downstream regulatory element antagonist modulator (DREAM) protein expression in the spinal cord of streptozotocin-induced painful diabetic neuropathy (PDN) rats following formalin injection. In this experimentation, 48 Sprague-Dawley male rats were randomly selected and divided into four groups: (n = 12): control, PDN, and ifenprodil-treated PDN rats at 0.5 μg or 1.0 μg for 7 days. Type I diabetes mellitus was then induced by injecting streptozotocin (60 mg/kg, i.p.) into the rats which were then over a 2-week period allowed to progress into the early phase of PDN. Ifenprodil was administered in PDN rats while saline was administered intrathecally in the control group. A formalin test was conducted during the fourth week to induce inflammatory nerve injury, in which the rats were sacrificed at 72 h post-formalin injection. The lumbar enlargement region (L4-L5) of the spinal cord was dissected for immunohistochemistry and western blot analyses. The results demonstrated a significant increase in formalin-induced flinching and licking behavior with an increased spinal expression of activated microglia, BDNF and DREAM proteins. It was also shown that the ifenprodil-treated rats following both doses reduced the extent of their flinching and duration of licking in PDN in a dose-dependent manner. As such, ifenprodil successfully demonstrated inhibition against microglia activation and suppressed the expression of BDNF and DREAM proteins in the spinal cord of PDN rats. In conclusion, ifenprodil may alleviate PDN by suppressing spinal microglia activation, BDNF and DREAM proteins.
Expressions of spinal microglia activation, BDNF, and DREAM proteins correlated with formalin-induced nociceptive responses in painful and painless diabetic neuropathy rats

Ismail CAN, Suppian R, Ab Aziz CB, Long I

Neuropeptides, 2020 Feb;79:102003.
PMID: 31902597 DOI: 10.1016/j.npep.2019.102003

The complications of diabetic polyneuropathy (DN) determines its level of severity. It may occur with distinctive clinical symptoms (painful DN) or appears undetected (painless DN). This study aimed to investigate microglia activation and signalling molecules brain-derived neurotrophic factor (BDNF) and downstream regulatory element antagonist modulator (DREAM) proteins in spinal cord of streptozotocin-induced diabetic neuropathy rats. Thirty male Sprague-Dawley rats (200-230 g) were randomly assigned into three groups: (1) control, (2) painful DN and (3) painless DN. The rats were induced with diabetes by single intraperitoneal injection of streptozotocin (60 mg/kg) whilst control rats received citrate buffer as a vehicle. Four weeks post-diabetic induction, the rats were induced with chronic inflammatory pain by intraplantar injection of 5% formalin and pain behaviour responses were recorded and assessed. Three days later, the rats were sacrificed and lumbar enlargement region of spinal cord was collected. The tissue was immunoreacted against OX-42 (microglia), BDNF and DREAM proteins, which was also quantified by western blotting. The results demonstrated that painful DN rats exhibited increased pain behaviour score peripherally and centrally with marked increase of spinal activated microglia, BDNF and DREAM proteins expressions compared to control group. In contrast, painless DN group demonstrated a significant reduction of pain behaviour score peripherally and centrally with significant reduction of spinal activated microglia, BDNF and DREAM proteins expressions. In conclusions, the spinal microglia activation, BDNF and DREAM proteins correlate with the pain behaviour responses between the variants of DN.
Fulltext Goat milk enhances memory of d-galactose-induced aging rats

Safdar A, Azman KF, Zakaria R, Ab Aziz CB, Rashid U

J Tradit Complement Med, 2021 Mar;11(2):117-122.
PMID: 33728271 DOI: 10.1016/j.jtcme.2020.02.005

Background and aim: Goat milk is a food of high nutritional value and has been proved to possess strong antioxidant and anti-inflammatory properties. However, thus far, little is known of its possible effects on brain especially on memory during aging. The aim of this study was to assess the effect of goat milk supplementation on memory in d-galactose-induced aging rat model.
Experimental procedure: Fifty-two male Sprague Dawley rats were randomly divided into four groups: 1) control group, 2) goat milk treated group, 3) d-galactose treated group, and 4) goat milk plus d-galactose treated group. Goat milk (1 g/kg orally) and/or d-galactose (120 mg/kg subcutaneously) were administered continuously for six weeks preceded and followed by novel object recognition and T-maze test.
Results and conclusion: Prior to goat milk and d-galactose administration, there was no significant difference (p > 0.05) in memory between all groups. Goat milk administration alone significantly increased short- and long-term memory (p
Fulltext Retraction notice to "Goat milk enhances memory of d-galactose-induced aging rats" [J Tradit Complement Med 11 (2021) 117-122]

Safdar A, Azman KF, Zakaria R, Ab Aziz CB, Rashid U

J Tradit Complement Med, 2021 Jul;11(4):381.
PMID: 34195033 DOI: 10.1016/j.jtcme.2021.06.003

[This retracts the article DOI: 10.1016/j.jtcme.2020.02.005.].
Fulltext Effects of different doses of complete Freund's adjuvant on nociceptive behaviour and inflammatory parameters in polyarthritic rat model mimicking rheumatoid arthritis

Noh ASM, Chuan TD, Khir NAM, Zin AAM, Ghazali AK, Long I, et al.

PLoS One, 2021;16(12):e0260423.
PMID: 34879087 DOI: 10.1371/journal.pone.0260423

Complete Freund's adjuvant (CFA) has been used to develop the arthritic or inflammatory condition in the animal, but there is a lack of information concerning high CFA doses on nociceptive behaviour and inflammatory parameters. This study aimed to compare the effects of different high doses of CFA in rat to closely mimic nociceptive and inflammatory parameters of rheumatoid arthritis (RA) in humans. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6): Control (C), CFA-induced polyarthritic groups at 5.0 mg/mL (CFA 5.0), 7.5 mg/mL (CFA 7.5) and 10.0mg/mL (CFA 10.0). The rats' right hindpaw was inoculated with CFA intradermally and developed into a polyarthritic state within 20 days. Nociceptive behavioural assessments, including von Frey and hot plate tests and spontaneous activities, were conducted on day 0, 7, 15 and 20. Bilateral ankle joints diameter and circumference, full blood count, joints and paw histological examinations were also conducted throughout the study period. Based on the results, CFA 5.0 and CFA 7.5 groups showed a significant increase in spontaneous activities and development of thermal hyperalgesia but no change in body weight and food intake, no development of tactile allodynia and haematological indices, and no significant morphological changes of joints histology. Meanwhile, CFA 10.0 group demonstrated significant and constant changes in all nociceptive and inflammatory parameters investigated. In conclusion, CFA at the dose of 10mg/mL has the most potential and reliable dosage to develop polyarthritis in a rat model to mimic RA condition in humans.
Screening of the LIX1 gene in Japanese and Malaysian patients with SMA and/or SMA-like disorder

Sasongko TH, Gunadi, Yusoff S, Atif AB, Fatemeh H, Rani A, et al.

Brain Dev, 2010 May;32(5):385-9.
PMID: 19664890 DOI: 10.1016/j.braindev.2009.06.008

The majority of spinal muscular atrophy (SMA) patients showed homozygous deletion or other mutations of SMN1. However, the genetic etiology of a significant number of SMA patients has not been clarified. Recently, mutation in the gene underlying cat SMA, limb expression 1 (LIX1), has been reported. Similarity in clinical and pathological features of cat and human SMA may give an insight into possible similarity of the genetic etiology.