Current Pharmaceutical Design - Volume 11, Issue 23, 2005

Antidepressant drugs have been widely used for many years to treat neuropathic pain, despite the rationale for their use was still unclear. We review recent insights into their mechanism of action, focusing on central and peripheral analgesic actions. Beside the traditional monoaminergic hypothesis, other pharmacological actions have been studied: antidepressants interfere with the opioid system, interact with the NMDA r Read More

Neuropathic pain is characterised by both positive (hyperalgesia and allodynia) and negative (sensory deficits) symptoms and remains intractable to many commonly used analgesics. Antiepileptics are increasingly utilised in the treatment of neuropathic pain. This class of drugs works via three major mechanisms of action in order to dampen neuronal hyperexcitability within the central nervous system: potentiation of GABA tran Read More

NMDA (N-methyl-D-aspartate) receptors are one class of ionotropic receptor for the ubiquitous excitatory neurotransmitter L-glutamate. The receptor is made up of four protein subunits combined from a larger library of proteins, which gives this receptor a great deal of variability. This explains the large number of modulatory sites, a variety of sites at which antagonists can interact, and therefore a number of potential Read More

Neuropathic pain can be difficult to treat clinically, as current therapies involve partial effectiveness and significant adverse effects. Following the development of preclinical models for neuropathic pain, significant advances have been made in understanding the neurobiology of neuropathic pain. This includes an appreciation of the molecular entities involved in initiation of pain, the role of particular afferents (small and large Read More

Subtypes of tetrodotoxin resistant voltage-gated sodium channels are involved in the development of certain types of neuropathic pains. After nerve injury hyperexcitability and spontaneous firing develop at the site of injury and also in the dorsal root ganglion cell bodies. This hyperexcitability results at least partly from accumulation of sodium channels at the site of injury. The facts that these sodium channels Read More

Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opioid specific signaling. Endogenous opioid systems were found to be represented in the regions involved in the no Read More

It is now widely accepted that airway inflammation is the key factor underlying the pathogenesis of asthma. While corticosteroids remain the most important anti-inflammatory treatment for asthma they are rather non-specific in their actions. Their use also raises concerns over side effects and compliance issues, particularly in children and adolescents. There is therefore much effort being made to develop novel more specific a Read More

In chronic arthritis synovial inflammation is usually accompanied by bone erosion. Due to resulting structural damage, bone erosion is major reason for disability of RA patients. Thus, drug therapy in arthritis is not only focussed on the control of synovial inflammation but also on preserving bone from structural damage. Bone erosion in arthritis is a consequence of synovial osteoclast formation. Therapeutic approaches, which inte Read More

Nitric oxide (NO) plays role in a great range of important functions in the organism, such as vasodilatation, relaxation of muscles, neurotransmission, neuromediation, and host defense reactions. In the upper airways, nasal cavities and paranasal sinuses are the main sources of this biological mediator. Although the exact role of NO in nasal physiology remains poorly understood, the functions are thought to be ho Read More

Foam cell formation from macrophages with subsequent fatty streak formation plays a key role in early atherogenesis. Foam cell formation is thought to be induced by Low Density Lipoproteins (LDL), including oxidized LDL (OxLDL) or minimally modified LDL (mmLDL). Understanding the molecular mechanisms involved in OxLDL- and mmLDL-induced foam cell formation is of fundamental importance for atherosclerosis a Read More