TY - JOUR
T1 - Nerve growth factor-induced muscle hyperalgesia facilitates ischaemic contraction-evoked pain
AU - Sørensen, L B
AU - Gazerani, P
AU - Graven-Nielsen, T
N1 - © 2019 European Pain Federation - EFIC®.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Background: Intramuscular injection of Nerve Growth Factor (NGF) may influence the responsiveness of active chemo-sensitive channels affecting muscle pain sensitivity. This double-blinded crossover study in healthy humans assessed contraction-evoked pain responses and pain sensitivity during acute ischaemia in the tibialis anterior (TA) muscle before and 24 hr after five distributed NGF injections (1 µg, 4 cm interval) compared with control injections (isotonic-saline). Methods: Twenty-one subjects participated in two experimental phases, each including five sessions over 7 days, with a gap of 4 weeks in-between. Muscle pain intensity evoked with daily functional tasks (Likert scale score) was collected using a paper diary. Pain intensity evoked by ischaemic and non-ischaemic contractions numerical rating scale (NRS) was collected at Day0 and Day1. Pressure pain thresholds (PPTs) on the TA were recorded before (Day0), 3 hr, 1, 3, and 7 days post-injection, and after the ischaemic-contractions and post-cuff deflation at Day0 and Day1. Results: Increased Likert scores of pain were present for 7 days after NGF compared to control injections (p <.05). Higher NRS pain scores of ischaemic-contractions were seen when contracting the muscle injected with NGF compared to baseline (p =.003) and control (p =.012). Pain during non-ischaemic contractions was not significantly affected by NGF injections. Decreased PPTs were found at 3 hr, Day1 and Day3 post-injection (p <.05) in both conditions. Compared with pre-contractions, PPTs were increased following ischaemic contractions at Day0 (p <.05) and Day1 (p <.05) in both conditions. Conclusion: This study showed that ischaemic contraction-evoked pain was facilitated in an NGF-sensitized muscle. Significance: Acidification of the muscle environment may affect muscle nociceptors and pain by different mechanisms, including activation of ASIC
3 and TRPV1. In this study, pain evoked following ischaemic contractions was increased in the Nerve Growth Factor (NGF)-sensitized muscle compared with non-ischaemic contractions and in the non-sensitized muscle. These findings illustrate that responses of peripheral afferents under ischaemic conditions are altered by a pre-sensitized muscle. This highlights the role of growth factors, including NGF, in peripheral muscle sensitization with clinical implications for ischaemic myalgia.
AB - Background: Intramuscular injection of Nerve Growth Factor (NGF) may influence the responsiveness of active chemo-sensitive channels affecting muscle pain sensitivity. This double-blinded crossover study in healthy humans assessed contraction-evoked pain responses and pain sensitivity during acute ischaemia in the tibialis anterior (TA) muscle before and 24 hr after five distributed NGF injections (1 µg, 4 cm interval) compared with control injections (isotonic-saline). Methods: Twenty-one subjects participated in two experimental phases, each including five sessions over 7 days, with a gap of 4 weeks in-between. Muscle pain intensity evoked with daily functional tasks (Likert scale score) was collected using a paper diary. Pain intensity evoked by ischaemic and non-ischaemic contractions numerical rating scale (NRS) was collected at Day0 and Day1. Pressure pain thresholds (PPTs) on the TA were recorded before (Day0), 3 hr, 1, 3, and 7 days post-injection, and after the ischaemic-contractions and post-cuff deflation at Day0 and Day1. Results: Increased Likert scores of pain were present for 7 days after NGF compared to control injections (p <.05). Higher NRS pain scores of ischaemic-contractions were seen when contracting the muscle injected with NGF compared to baseline (p =.003) and control (p =.012). Pain during non-ischaemic contractions was not significantly affected by NGF injections. Decreased PPTs were found at 3 hr, Day1 and Day3 post-injection (p <.05) in both conditions. Compared with pre-contractions, PPTs were increased following ischaemic contractions at Day0 (p <.05) and Day1 (p <.05) in both conditions. Conclusion: This study showed that ischaemic contraction-evoked pain was facilitated in an NGF-sensitized muscle. Significance: Acidification of the muscle environment may affect muscle nociceptors and pain by different mechanisms, including activation of ASIC
3 and TRPV1. In this study, pain evoked following ischaemic contractions was increased in the Nerve Growth Factor (NGF)-sensitized muscle compared with non-ischaemic contractions and in the non-sensitized muscle. These findings illustrate that responses of peripheral afferents under ischaemic conditions are altered by a pre-sensitized muscle. This highlights the role of growth factors, including NGF, in peripheral muscle sensitization with clinical implications for ischaemic myalgia.
UR - http://www.scopus.com/inward/record.url?scp=85070525227&partnerID=8YFLogxK
U2 - 10.1002/ejp.1455
DO - 10.1002/ejp.1455
M3 - Journal article
C2 - 31314952
SN - 1090-3801
VL - 23
SP - 1814
EP - 1825
JO - European Journal of Pain
JF - European Journal of Pain
IS - 10
ER -