Highlights
- •Distributed low-dose NGF injections induce pronounced muscle hypersensitivity
- •Distributed NGF injections affect a larger muscle area compared to single-bolus NGF
- •Low-dose NGF sensitize muscle nociceptors locally
- •Distributed NGF may mimic clinical pain better as a larger muscle area is affected
Abstract
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 (5 µg) compared with 5 spatially distributed,
low-dose NGF injections (1 µg, 4 cm distance) into the tibialis anterior (TA) muscles
in 20 healthy subjects. Injection pain was rated on a visual analog scale. Reports
of muscle pain with functional tasks (Likert scale score) and the presence of spontaneous
pain were collected daily by using a diary. Pressure pain threshold (PPT), overall
pain intensity (numerical rating scale), and pain areas following the TA contraction
were collected at baseline; 3 hours; and 1, 3, 7, 14, and 21 days postinjection. Low
immediate visual analog scale scores were associated with both injection protocols.
Likert scale scores showed moderate pain intensities but no spontaneous pain, until
day 12, for both injection protocols (P < .05). Reduced PPTs at the 5- and 1-µg injection sites were found after 3 hours,
lasting until day 7 (P < .05). The 1-µg injection provoked decreased PPTs at day 1 (P = .036) at the proximal injection site and at day 1 (P = .02) and day 3 (P = .01) at the distal injection site. The TA muscle contraction resulted in larger
pain areas and higher numerical rating scale scores at day 3 for the distributed injections
compared with the single-site injection (P < .001).
Perspective: 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 in which diffuse pain areas and
muscle hypersensitivity are present during the activities of daily living. Low-dose
NGF injections may be useful for further studies of prolonged pain conditions.
Key words
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Article info
Publication history
Published online: December 01, 2018
Accepted:
November 13,
2018
Received in revised form:
October 26,
2018
Received:
August 13,
2018
Footnotes
CNAP is supported by the Danish National Research Foundation (DNRF121).
The authors have no conflicts of interest to declare.
Identification
Copyright
© 2018 by the American Pain Society
