Research & Drug Development

Neuropathic pain is a chronic, frequently progressive condition that seriously impacts the quality of life of patients who suffer from it.  The disease is caused by damage to, or dysfunction of, the nervous system and typically results from damage to nerve cells.

Different people experience different symptoms of this disease. The most common is a tingling in the toes or fingers, which spreads up the body and may intensify to a burning sensation or ‘pins and needles’. These sensations may occur constantly, or periodically, and can be very painful or make the area very sensitive to other stimuli that result in feeling everything in an exaggerated way, so that even gentle stimuli cause pain or irritation (allodynia). Painful stimuli are also perceived in an exaggerated way (hyperalgesia).

A range of causes are connected with neuropathic pain, though in many cases a cause cannot be established. One of the most common causes of neuropathic pain are trauma direct to the nerves and diabetes mellitus. Other causes include alcohol abuse, poor blood supply to the hands and feet, vitamin B12 deficiency, toxic substances, liver disease, kidney disease and certain infections, such as leprosy and HIV. In some cases neuropathic pain is hereditary and may occur alongside problems with other parts of the nervous system. The mechanism through which these factors cause the neuropathic pain is not well understood.

As the disease is caused by a lesion in the nervous system, most frequently in the peripheral nerves but also occasionally in the pathways that carry the sensation to brain and elaborate the pain sensation, thus neuropathic pain is distinguished in two main forms: the one with peripheral origin and the other of central origin. A form of “central neuropathic pain” is seen when a cerebro vascular accident involves part of the thalamus, a structure of the brain that elaborates pain perception. In these cases excruciating pain is perceived in parts of the body opposite to the site of the affected thalamus. A mixed form of central and peripheral neuropathic pain is termed the “phantom limb”. After a peripheral lesion of the nerves, mostly as a consequence of amputation, the residual stump re-grows disorderly. Abnormal impulses generated from the stump travel to the brain building up a self-sustained circuit projecting the image of the missing limb. Thus, the patient still perceives the limb as if it were intact.

Similarly to what happens in epilepsy, the injured area sends abnormal messages. These signals are created using channels in the neuronal membrane that selectively allows the passage of specific ions (atoms electrically charged), thereby generating currents that trigger the firing of nerves.

Although there is no single definition of neuropathic pain, approximately 26 million patients worldwide suffer from some form of the condition (Espicom, 2005). As the currently available treatments for neuropathic pain provide only partial pain relief, there is a strong need for new agents with novel mechanisms of action that lead to improved drug profiles.