Strategic research on pains and headaches

Abstract

Pain and headache are common problems in clinical practice. In general, pain can be classified as nociceptive or neuropathic pain. In nociceptive pain, the unpleasant symptom is caused by noxious stimulation leading to tissue injuries. Various chemical mediators are involved in the process of inflammation occurred in the injured tissue. These chemicals induce significant changes in neurons in several levels of neural pathways involving in the nociceptive processing. Increased excitability of neurons known as ‘peripheral and central sensitization’ is now believed to be the utmost important mechanisms in development of chronic pain. In neuropathic pain, the pain is caused by alteration of neuronal excitability which results in the increase neural firing in the nociceptive pathway. This type of pain can be secondary to the structural change in neural pathway such as nerve injuries, ischemia in path processing are such as thalamus, etc. It can also occur after prolonged exposure to noxious stimulation which induces secondary change in the neuronal pathway. Similar to pain, headache can be classifies as primary and secondary headaches. In the recent years, several remarkable discoveries have been reported which can increase our understanding in the pathogenesis of primary headache. Our Chulalongkorn Headache Research Group has shown that the excitability of cortical neurons is increased in animal model of medication-overuse headache. Cortical hyperexcitability may facilitate the development of cortical spreading depression, while increased excitability of trigeminal neurons may facilitate the process of peripheral and central sensitization. These changes may be secondary to the derangement of central, probably serotonin (5-HT)-, and perhaps endocannabinoid-dependent or other, modulating systems. Increased expression of excitatory cortical 5-HT2A receptors may increase the susceptibility to developing cortical spreading depression, an analog of migraine aura. A reduction of diffuse noxious inhibitory controls may facilitate the process of central sensitization, activate the nociceptive facilitating system, or promote similar molecular mechanisms to those involved in kindling. Low 5-HT levels also increase the expression and release of calcitonin gene-related peptide from the trigeminal ganglion and sensitize trigeminal nociceptors. Thus, derangement of central modulation of the trigeminal system as a result of chronic medication use may increase sensitivity to pain perception and foster or reinforce medication overuse headache.