Research & Drug Development

Inflammatory pain is precipitated by an insult to the integrity of tissues at a cellular level. This can happen with penetration wounds, burns, extreme cold, fractures, arthritis, autoimmune conditions, excessive stretching, infections and vasoconstriction. During inflammation a complex neuro-immune interaction results in primary hyperalgesia. A large range of inflammatory molecules induce and maintain the altered nociceptor sensitivity observed as hyperalgesia. This has been called the inflammatory soup. These include compounds released or synthesised as a result of cellular breakdown, such as prostaglandins and bradykinin. The hyperaemia associated with inflammation delivers further mediators of hyperalgesia such as nitric oxide and bradykinin precursors. The primary afferent neuron itself secretes neuropeptides which can cause sensitisation. Immune cells secrete a range of both pro- (e.g. cytokines, neurotrophins, serotonin and histamine) and anti-hyperalgesic molecules (e.g. opioids and cannabinoids).

This chemical soup of inflammatory mediators can directly affect nociceptors or may sensitize them to touch or movement, even at some distance from the inflammatory field. In this way one inflammatory mediator may sensitize more distant pain receptors to another inflammatory mediator.

Inflammation-induced central sensitization, characterized by an enhanced neuronal activity in the spinal dorsal, is also an important component of inflammatory pain.

Rheumatoid (RA) and osteoarthritis (OA) are chronic, debilitating diseases. Pain in both of these conditions is generally perceived to arise from inflammation, but emerging data indicate that RA/OA pain results from a combination of peripheral and central mechanisms, being central sensitization involved. Pain control could be improved by blocking both the cascade that leads to initiation/amplification of inflammatory processes and maintenance of central sensitization. Pain in OA and RA is characterized by spontaneous pain as well as lowered pain thresholds and increased sensitivity to pressure and temperature. Osteoarthritis (OA) related pain affects roughly 47 million patients across the 7 major pharmaceutical markets (Reuters, 2004).