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Spatial and temporal aspects of muscle hyperalgesia induced by nerve growth factor in humans

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Abstract

Intramuscular injection of nerve growth factor (NGF) has been shown to induce long-term sensitisation and time-dependent hyperalgesia indicating potential involvement of both central and peripheral pain mechanisms. This double-blind placebo-controlled study was designed to describe the spatial distribution of muscle hyperalgesia over time (immediately after, 3 h, 1, 4, 7 and 21 days) after injecting NGF (5 μg) into the tibialis anterior (TA) muscle, to explore possibly involved central pain mechanisms and to investigate the effect of gender on development of hyperalgesia. Totally 20 healthy volunteers (10 men and 10 women) participated in the study. An isotonic saline injection into the contralateral TA muscle served as a control condition for the NGF injection. Pressure pain thresholds (PPT) were used to test for muscle hyperalgesia along the TA (seven sites) muscle at the extensor digitorum longus and at the web between 1st and 2nd metatarsal (central involvement). One day after the NGF/control injections, hypertonic saline (0.5 ml, 5.8%) was injected into the left and right TA to study the pain response to chemical stimulation of the hyperalgesic muscle tissue. Scores on a modified Likert scale were used to assess soreness during muscle function. An area of hyperalgesia was observed locally at the injected site 3 h after injection of NGF, which expanded both proximally and distally on day 1; this effect subsided on day 4. Decreased PPT was also found between 1st and 2nd metatarsal on day 1. Hypertonic saline evoked more pain in men when injected in the NGF treated TA compared to the control leg. Injection of NGF increased muscle soreness during muscle activity for 7 days. In this material there was no gender effect of NGF-induced muscle hyperalgesia. The expansion of muscle hyperalgesia to distant areas indicates that central mechanisms are involved.

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Acknowledgments

The authors are grateful to Dr. John Hansen (Center for Sensory-Motor Interaction (SMI), Aalborg University, Denmark) for invaluable help with software development and hardness analysis. This study was supported by the Oak Foundation, Sundheds CVU Nordjylland and the CW Obel’s Foundation.

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Authors and Affiliations

  1. Laboratory for Musculoskeletal Pain and Motor Control, Center for Sensory–Motor Interaction (SMI), Aalborg University, Fredrik Bajers Vej 7-D, 9220, Aalborg E, Denmark

    Helle Andersen, Lars Arendt-Nielsen & Thomas Graven-Nielsen

  2. Department of Clinical Oral Physiology, Dental School, University of Aarhus, Aarhus, Denmark

    Peter Svensson

  3. The Parker Institute, Frederiksberg Hospital, Frederiksberg, Denmark

    Bente Danneskiold-Samsøe

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  1. Helle Andersen
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  2. Lars Arendt-Nielsen
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  4. Bente Danneskiold-Samsøe
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  5. Thomas Graven-Nielsen
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Correspondence to Thomas Graven-Nielsen.

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Andersen, H., Arendt-Nielsen, L., Svensson, P. et al. Spatial and temporal aspects of muscle hyperalgesia induced by nerve growth factor in humans. Exp Brain Res 191, 371–382 (2008). https://doi.org/10.1007/s00221-008-1531-5

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