Time Course and Dose-Dependence of Nerve Growth Factor–Induced Secondary Hyperalgesia in the Mouse

Administration of the neurotrophin nerve growth factor (NGF) to rats and humans has been shown to induce both thermal and mechanical hyperalgesia and is used as a model of inflammatory pain. Here we describe a mouse model of secondary hyperalgesia after NGF application. NGF was injected into the biceps femoris muscle unilaterally, and at various intervals afterwards the electromyographic (EMG) activity from the same muscle was recorded in response to mechanical von Frey hair stimulation of the plantar surface of the hind paw in isoflurane-anesthetized mice. Secondary cutaneous hyperalgesia in the hind paw reached a peak 60 minutes after injection and returned to baseline levels after an additional 60 minutes. This was followed by a second increase in EMG magnitude at 24 hours after injection that was still present after 5 days. The effects of NGF were dose-dependent, and a dose of 2 μg/g NGF had the maximal observed effect. No increase in EMG magnitude occurred on the untreated side. This study describes a quantitative mouse model of prolonged secondary cutaneous hyperalgesia after NGF-induced muscle inflammation that can be used for genetic manipulations of putative central molecular pathways that underlie secondary hyperalgesia.PerspectiveThis study describes the development of a novel model of NGF-induced secondary hyperalgesia. The development of this model will allow further investigations into the processes that underlie the development of secondary hyperalgesia and pain associated with the musculature.