Attenuation of Spinal Cord Injury-induced Hyperalgesia by Administration of Antibody to Nerve Growtb Factor in the Rat

Background: Spinal cord injury (SCI) often leads to central pain syndrome, including hyperalgesia to mechanical stimulation. Since there is evidence that nerve growth factor (NGF) contributes to pain-related behaviors, we wanted to determine if anti-NGF might inhibit the abnormal somatosensory behaviors that develop following SCI in rats. Methods: SCI was performed in male Sprague Dawley rats by T13 spinal hemisection. After the spinal hemisection, the animals were treated daily with anti-NGF or saline intraperitoneally for 10 days or left untreated. Extracellular recordings of neuronal activity were made from the dorsal horn neurons in the lumbar spinal cord (L4-L5), using a recording glass microelectrode. The single unit responses of the neurons to mechanical stimuli, applied to the receptive fields, were analyzed. The wide dynamic range (WDR) neurons, which were characterized by their graded responses to increased intensities of mechanical stimuli, were subjected to the investigation. Results: In both the hemisection only and hemisection with saline treatment groups, mechanical hyperalgesia developed in both hind limbs, as evidenced by a decrease in the paw withdrawal thresholds. The mechanical responsiveness of the WDR neurons on both sides of the spinal cord also increased. The anti-NGF treated group demonstrated significant suppression of both the mechanical hyperalgesia and increased WDR neuronal responsiveness. Conclusions: These results indicate that anti-NGF prevents the development of abnormal somatosensory behavior, suggestive of a potential pre-emptive analgesic treatment for central pain.