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Pain. 2013 Nov;154(11):2344-52. doi: 10.1016/j.pain.2013.07.007. Epub 2013 Jul 16.

Repeated intramuscular injections of nerve growth factor induced progressive muscle hyperalgesia, facilitated temporal summation, and expanded pain areas.

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Laboratory for Musculoskeletal Pain and Motor Control, Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark; Department of Functional Anatomy, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, Japan.


Intramuscular injection of nerve growth factor (NGF) is known to induce deep-tissue mechanical hyperalgesia. In this study it was hypothesised that daily intramuscular injections of NGF produce a progressive manifestation of soreness, mechanical hyperalgesia, and temporal summation of pain. In a double-blind placebo-controlled design, 12 healthy subjects were injected on 3 days with NGF into the tibialis anterior muscle and with isotonic saline on the contralateral side. Assessments were performed before and after the injections on days 0, 1, and 2, and repeated on days 3, 6, and 10. The self-perceived muscle soreness was assessed on a Likert scale. Computer-controlled pressure algometry was used to assess the pressure pain thresholds (PPTs). Temporal summation of pain after repeated pressure stimulations was assessed by computer-controlled pressure algometry. The pain distribution following painful pressure stimulation was also recorded. Compared with baseline and isotonic saline, the NGF injections caused (P<0.05): (1) progressively increasing soreness scores from 3 hours after the first injection until day 2, after which it remained increased; (2) decreased PPTs at days 1 to 3; (3) facilitated temporal summation of pressure pain at days 1 to 10; and (4) enlarged pressure-induced pain area after the injection on day 1 to day 6. The daily injections of NGF produced a progressive manifestation of muscle soreness, mechanical hyperalgesia, temporal summation of pressure pain, and pressure-induced pain distribution. These data illustrate that the prolonged NGF application affects peripheral and central mechanisms and may reflect process in musculoskeletal pain conditions.


Muscle hyperalgesia; Nerve growth factor (NGF); Referred pain; Soreness; Temporal summation

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