ENLARGED AREAS OF PAIN AND PRESSURE HYPERSENSITIVITY BY SPATIALLY DISTRIBUTED INTRAMUSCULAR INJECTIONS OF LOW-DOSE NERVE GROWTH FACTOR.

Intramuscular injection of nerve growth factor (NGF) causes muscle hyperalgesia without immediate pain. This double-blinded, randomized study assessed pain and muscle hypersensitivity after a single-site bolus NGF injection (5µg) compared with five spatially distributed, low-dose NGF injections (1µg, 4cm distance) into the tibialis anterior (TA) muscles in 20 healthy subjects. Injection-pain was rated on a visual analogue scale (VAS). Reports of muscle pain with functional tasks (Likert scale score) and presence of spontaneous pain were collected daily using a diary. Pressure pain threshold (PPTs), overall pain intensity (numerical rating scale, NRS) and pain areas following TA contraction were collected at baseline, 3 hours, 1, 3, 7, 14, and 21 days post-injection. Low immediate VAS-scores were associated with both injection protocols. Likert scores showed moderate pain intensities, but no spontaneous pain, until Day12 for both injection-protocols (P<0.05). Reduced PPTs at the 5µg and 1µg injection sites were found after 3 hours lasting until Day7 (P<0.05). The 1µg injection provoked decreased PPTs at Day1 (P=0.036) at proximal injection-site, and at Day1 (P=0.02) and Day3 (P=0.01) at distal injection-site. TA muscle contraction resulted in larger pain areas and higher NRS scores at Day3 for the distributed injections compared with the single-site injection (P<0.001). PERSPECTIVES: Spatially distributed low-dose NGF injections induced prolonged pain, mechanical muscle hypersensitivity and enlarged contraction-evoked pain areas. These features mirror some clinical muscle pain conditions where diffuse pain areas and muscle hypersensitivity is present during daily activities. Low-dose NGF injections may be useful for further studies of prolonged pain conditions.