NGF over-expression during development leads to permanent alterations in innervation in the spinal cord and in behavioural responses to sensory stimuli

Transgenic mice expressing nerve growth factor (NGF) under the control of a myelin basic protein promoter display above normal NGF levels in the spinal white matter from birth to the age of 2 months. These transient high levels of NGF result in a lasting hyper-innervation of the spinal white matter by ectopic Substance P (SP)-immunoreactive (IR) sensory fibres. Ultrastructural studies in adult transgenic mice demonstrated that the SP-containing fibres establish synapses on neuronal dendrites in the white matter and that most such dendrites express SP receptors. The transgenic animals display a stimulus-induced hyperalgesia and allodynia in a test measuring the latency to tail withdrawal following a heat stimulus. The hyperalgesia and allodynia were reversed by systemic administration of SP receptor or NMDA receptor antagonists. Surprisingly, the application of morphine resulted in an increase in withdrawal latency which was greater than that observed in non-transgenic controls.