TY - JOUR
T1 - Enlarged areas of pain and pressure hypersensitivity by spatially distributed intramuscular injections of low-dose nerve growth factor
AU - Sørensen, Line Bay
AU - Christensen, Shellie
AU - Gazerani, Parisa
AU - Graven-Nielsen, Thomas
N1 - DNRF121
Copyright © 2018 the American Pain Society. Published by Elsevier Inc. All rights reserved.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - Nerve growth factor
KW - hyperalgesia
KW - injection
KW - muscle contraction
KW - pain measurements
UR - http://www.scopus.com/inward/record.url?scp=85060332946&partnerID=8YFLogxK
U2 - 10.1016/j.jpain.2018.11.005
DO - 10.1016/j.jpain.2018.11.005
M3 - Journal article
C2 - 30513347
SN - 1526-5900
VL - 20
SP - 566
EP - 576
JO - Journal of Pain
JF - Journal of Pain
IS - 5
ER -