<img height="1" width="1" style="display:none;" alt="" src="https://dc.ads.linkedin.com/collect/?pid=217082&amp;fmt=gif">

MD Biosciences Blog

MS Whitepaper: EAE Models | Evaluating Neuroprotective Treatment

Posted by MD Biosciences on Apr 20, 2010 9:12:00 AM

Cognitive impairment is common in multiple sclerosis (MS), occuring at all stages of disease. It is a main source of disability, social impairment and has a great impact on an individuals quality of life. In the clinic, factors that can affect MS-related cognitive impairment are disease course, fatigue, and affective disturbance.  While the neurochemical basis underlying motor and cognitive defects in patients with MS is unclear, it appears that a balance of tissue destruction, tissue repair and adaptive function reorganization are related to the degree of impairment.

Its most commonly believed that MS is an autoimmune disease in which the body's own immune system recognizes myelin proteins or myelin related proteins as foreign and marks them for destruction. In the body's periphery, major histocompatibility complex (MHC) Class II proteins expressed on the surface of antigen presenting cells (APC) mistakenly bind to these proteins. This causes a naive-T (Th0) to bind to the antige and undergo activation and differentiation. Adhesion molecules and matrix metalloproteinases (MMPs) help T-helper 1 (TH1) cells stick and penetrate the blood brain barrier (BBB) into the CNS, they engage antigen-MHC complexes and produce pro-inflammatory cytokines leading to damage in the CNS. 

Read More

Topics: Inflammation, Neuro/CNS

Why Post-operative Pain Is Under-Treated

Posted by MD Biosciences on Mar 23, 2010 9:22:00 AM

Adequate pain relief following surgical procedures is well-documented to improve the degree and time course of patient recovery. Nontheless, post-operative pain remains grossly under treated, with up to 70% of patients reporting moderate to severe pain following surgery (1). Perhaps the biggest underlying contributor to the under treatment of post-operative pain is simply a lack of information, both on the part of basic scientists as well as clinicians. Scientists are in the relatively early stages of investigation into the specific mechanisms contributing to the development of incisional pain, which may differ from those mediating acute pain induced by chemical or inflammatory algesic agents. Currently, clinicians essentially rely on treatments that have been developed for other painful conditions, most notably opioids, the side effects of which can hinder rehabilitation and recovery. 

Read More

Topics: Pain

Pain Processing: Cation Channel Blockers. Choosing Pain Models

Posted by MD Biosciences on Jan 11, 2010 11:54:00 AM

Sodium and calcium cation channel blockers.

Read More

Topics: Pain

Cannabinoid System | A Target For Pain Relief.

Posted by MD Biosciences on Nov 17, 2009 2:00:00 PM

The body's cannabinoid system consists of two cannabinoid receptors, CB1 and CB2, their endogenous ligands, which include 2-arachidonoyl glycerol (2-AG) and anandamide (AEA), and the enzymes that regulate the synthesis and degradation of these ligands. While the endogenous cannabinoid system serves naturally to modulate pain transmission, it can be exploited to provide more robust relief, either through administration of agonists at CB1 or CB2 receptors or through inhibition of degrading enzymes to increase endogenous cannabinoid levels.

CB1 receptors are expressed in neurons throughout the central and peripheral nervous system, including in the DRG, where noiciceptor cell bodies reside, the dorsal horn of the spinal cord, and the PAG, all of which are important sites for modulation of pain transmission. CB2 receptors, on the other hand, are not found in the CNS under normal conditions (although they may be upregulated in nociceptive neurons after injury) and are instead expressed in a variety immune cells and microglia. Although activation of either receptor can promote pain relief, CB1 receptors are responsible for the centrally-mediated psychomimetic side effects that sometimes accompany administration of cannabinoid receptor agonists such as tetrahydrocannabinol (THC).

Both CB1 and CB2 are GPCRs that signal predominantly through Gi/o to decrease VGCC conductance and activate GIRKs to hyperpolarize cells. Therefore, ligand binding to cannabinoid receptors results in decreased release of excitatory neurotransmitters from nociceptive neurons and post-synaptic cells exhibiting decreased excitability for signals they do receive. Activation of cannabinoid receptors on immune cells can similarly inhibit their function and thereby indirectly modulate pain processing. Since CB2 receptors are found primarily on immune cells and microglia, this indirect, anti-inflammatory effect is the primary mechanism by which CB2-selective agonists modulate pain responses.

Cannabinoid agonists have shown efficacy in acute models such as tail flick and capsaicin injection, as well as carrageenan and CFA inflammatory pain models. Translation from animal models to the human condition has been documented for a variety of neuropathic conditions as well as for post-operative pain relief; therefore, both neuropathic and post-operative pain models would be appropriate for testing novel compounds designed to target the cannabinoid system as well.
Read More

Topics: Pain

α2-adrenergic Agonists & Tricyclic Antidepressants | Pain Model

Posted by MD Biosciences on Oct 14, 2009 2:14:00 PM

α2-adrenergic receptors (α2ARs) are found in many areas in throughout the nervous system, but the α2ARs on pre- and post-synaptic neurons in the dorsal horn of the spinal cord are the main target for both endogenous and exogenous analgesia. One of the major descending inhibitory pain pathways involves the projection of noradrenergic neurons in the locus ceruleus back down to the spinal cord to activate α2ARs at this site. These receptors can also be targeted pharmacologically through administration of selective agonists or through the inhibition of noradrenaline (also known as norepinephrine) reuptake by drugs such as tricyclic antidepressants.

Read More

Topics: Pain