Chronic pain affects 40-70 million Americans each year and can be classified as nociceptive (caused by tissue injury or inflammation), neuropathic (caused by damage to the nervous system, e.g., by trauma, disease, chemicals or surgery) or a mixture of nociceptive and neuropathic such as associated with a number of other common chronic conditions (e.g., cancer, osteoarthritis, low back pain). Whatever the cause, chronic pain is particularly troubling as it sparks a viscous cycle of clinical problems and often precipitates depression and/or life-style changes. Furthermore, establishing prolonged analgesia free of serious side effects is a particularly challenging area of medicine. The total economic cost of pain is US$100 billion and the global market of analgesics and anti-inflammatories has been estimated as US$18.7 billion worldwide. Pain, especially nociceptive pain, is currently treated by NSAIDs or by opiates both of which may produce serious adverse effects and further clinical options are therefore required. The entire future of pain therapeutics continues to be a major priority of the pharmaceutical industry.

A number of research groups have recently described the anti-nociceptive properties of brain-derived neurotrophic factor (BDNF), a molecule that has more commonly been associated with neuronal development than pain. Previous studies have shown that peripheral inflammation increases expression of BDNF preferentially in dorsal root ganglion cells and furthermore, expression of the tyrosine kinase receptor that selectively binds BDNF, trkB, is also increased in the spinal dorsal horn during inflammation. Moreover, the removal of BDNF attenuates inflammation-induced behavioral responses. Most recently, one US based group has shown that BDNF or a second trkB ligand, neurotrophin-4/5, produces an acute, dose-dependent thermal hyperalgesic response. Selective inhibition of BDNF or trkB expression produces antinociception in normal mice and attenuates carrageenan-induced hyperalgesia. Interestingly, this group suggests that the effects of BDNF involve central sensitization in a process dependent on NMDA receptor activation. This data suggests that BDNF may represent a target for the treatment of inflammatory pain although caution should be applied since BDNF has been associated with both hyperalgesia and antinociceptive activity in the context of neuropathic pain.

December, 2002

Adapted from Groth & Aanonsen, Pain 2002 Nov;100(1-2):171-81

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