Molecular mechanisms underlying pain.

Pain continues to be a major health problem with tremendous financial, social and psychological costs. Conservative estimates put the cost of pain to the US economy well into the hundreds of billions of dollars per year as a result of associated medical expenses and lost wages with a significant minority of Americans suffering from persistent or recurrent pain syndromes throughout the most productive years of their lives. Just one pain syndrome, migraine headache, directly impacts 20% of the adult population. Yet, there remain few if any effective therapies devoid of serious side effects that are currently available to treat pain, particularly persistent or recurrent pain associated with syndromes.

The clinical features of a number of pain syndromes serve as the organizing focus of research in the Gold laboratory. These observations include the following:

1. many pain syndromes are unique to a particular part of the body such as the head in migraine, the temporomandibular joint in temporomandibular disorder (TMD), or the colon in inflammatory bowel disease (IBD).
2. many pain syndromes such as migraine, TMD and IBD occur with a greater prevalence, severity and/or duration in women than in men.
3. many pain syndromes are associated with changes in the excitability of primary afferent neurons.
4. there are time dependent changes in the mechanisms underlying pain syndromes.
5. the type of injury, (i.e., inflammation or nerve injury), are differentially sensitive to therapeutic interventions.

These observations led to specific hypotheses that are tested in ongoing studies in the Gold laboratory. These include:

1. characterizing the mechanisms underlying inflammation-induced changes in the evoked Ca2+ transients in sensory neurons.
2. characterizing the mechanisms underlying the inflammatory mediator-induced sensitization of dural afferents.
3. characterizing the influence of estrogen on the excitability of spinal and trigeminal ganglion neurons.
4. characterizing the mechanisms underlying the link between stress and migraine.
5. characterizing the role of changes in inhibitory receptors, in particular GABA, in injury-induced increases in sensitivity.
6. identification of ways to maximize the therapeutic utility of local anesthetics.

The ultimate goal of these studies is to identify novel targets for the development of therapeutic interventions for the treatment of pain.