Neurotrophic factors and pain

Neurotrophic factors have been shown to play significant roles in the transmission of physiologic and pathologic pain. Nerve growth factor appears to be particularly important. It is crucial for the development of sympathetic and small fiber sensory neurons that serve as nociceptors. It stimulates the expression and release of neuropeptides involved in pain transmission, and interacts with cellular and molecular mediators of inflammation. Blockade with nerve growth factor antiserum demonstrates the critical role of the growth factor in mediating inflammatory hyperalgesia. Administration of nerve growth factor to rodents results in the rapid onset of hyperalgesia. Although the exact mechanism is unknown, several possibilities have been proposed. In clinical trials for the treatment of Alzheimer disease and peripheral neuropathy, induction of pain has been the major adverse event. When administered intracebrebroventricularly, a dull constant back pain resulted. Subcutaneous injection of nerve growth factor induces injection site hyperalgesia, as well as generalized myalgias and arthralgias. Whether the mechanisms underlying these adverse events are identical to those associated with the hyperalgesia in rodents is unknown. In addition to nerve growth factor, other growth factors, such as brain-derived neurotrophic factor and glial cell-derived neurotrophic factor, may be involved in pain pathways. Their precise roles are still being defined, but evidence suggests that they may have particular relevance to neuropathic pain. Understanding the role all these factors play may change the way we approach the treatment of pain in general, and neuropathic pain in particular.