INTRADERMAL RECOMBINANT HUMAN NERVE GROWTH-FACTOR INDUCES PRESSURE ALLODYNIA AND LOWERED HEAT-PAIN THRESHOLD IN HUMANS

Nerve growth factor (NGF) plays a biologic role in the development and maintenance of sympathetic and small sensory neurons. Because it faci litates nerve fiber regeneration, lowers heat-pain threshold (hyperalg esia), and prevents or improves nerve dysfunction in experimental neur opathy, it is being considered as a putative treatment for certain hum an polyneuropathies. In 16 healthy subjects, we tested whether intrade rmal injection of minute doses of recombinant human NGF (1 or 3 mu g) compared with saline induces hyperalgesia or alters cutaneous sensatio n (at the site of injection) as measured by symptom scores, clinical e xamination, or quantitative sensory testing with Computer Assisted Sen sory Examination (CASE IV). Most subjects had, as their only symptom, localized tenderness of the NGF-injected site and only when the site w as bumped or compressed. Slight discomfort developed in volar wrist st ructures (with flexion of fingers) or tenderness of deep structures to palpation over the bicipital groove or supraclavicular region. The Ne uropathy Symptoms and Change questionnaire indicated that pressure all odynia was significantly localized to the NGF-injected side from 3 hou rs to 21 days after injections. Light stroking of the skin did not ind uce tactile allodynia. Compression of injected sites induced pressure allodynia that occurred more frequently and significantly on the NGF-i njected side after 3 hours and was maintained for several weeks. No ab normality of vibratory or cooling detection threshold developed from N GF injection. By contrast, heat-pain threshold (HP 0.5, p = 0.003) and an intermediate level of heat-pain (HP 5.0, p < 0.001) were significa ntly lowered 1, 3, and 7 days (and in some cases at 3 hours and 14 and 21 days) after NGF injection. The time course of pressure allodynia a nd heat-pain hyperalgesia is too rapid to be explained by uptake of NG F by nociception terminals, retrograde transport, and upregulation of pain modulators. Local tissue mechanisms appear to be implicated. It r emains to be tested whether recombinant human NGF prevents, stabilizes , or ameliorates small fiber human neuropathies.