Inflammation of the rat urinary bladder is associated with a referred thermal hyperalgesia which is nerve growth factor dependent

We have assessed whether a referred somatic hyperalgesia to thermal stimulation of the hind limb of rats occurs after inflammation of the urinary bladder. Furthermore, we evaluated whether any such viscero-somatic hyperalgesia (VSH) is dependent on the neurotrophin nerve growth factor (NGF). Limb withdrawal thresholds from thermal stimulation of both fore and hind limbs were assessed simultaneously at baseline and at fixed times for 24 h after various interventions. After plotting curves for the difference in withdrawal time of fore and hind limbs against time, the area under the curve (AUC) was calculated to provide a single measure over the 24-h period. A negative value indicated relative hyperalgesia of the hind limb. With simple catheterization, although there was a trend towards hind limb hyperalgesia, there was no significant difference in this AUC (mean -100.5) compared with naive control animals (mean AUC +53.6). However, inflammation with 50% turpentine oil was associated with a significant change in AUC (mean -676.8), indicative of relative hyperalgesia of the hind limb. This hyperalgesia was mimicked by intra-vesical instillation of NGF (in place of turpentine) (mean AUC -1418.3 while mean AUC in naive animals was +439.4). Furthermore, prior administration of an NGF sequestering molecule, trkA-IgG, attenuated turpentine-induced VSH. These findings increase our knowledge of the nature of visceral and referred pain and further implicate NGF in the hyperalgesic response to inflammation of the urinary bladder.