Visceral inflammation and somatic pain sensation

Visceral inflammation is frequently associated with changes in sensory pathways that lead to increased sensitivity to innocuous or noxious stimuli applied to peripheral structures. This dissertation reports the occurrence of peripheral mechanical sensitization during acute and chronic cystitis in rodents. First, we established acute and chronic models of cystitis that incited consistent bladder inflammation and reduced the threshold to sensation to mechanical stimuli applied to the hind paws. We then showed that nerve growth factor (NGF) partially mediates peripheral mechanical sensitivity that accompanies experimental cystitis in rodents. We also investigated brain-derived neurotrophic factor (BDNF) as having a potential role in inducing transient or persistent plastic changes that contribute to mechanical hypersensitivity in these models. Cystitis did not induce an increase in BDNF protein content within the bladder, and in contrast to control rats, BDNF was reduced in L6/S1 dorsal root ganglia (DRG) by acute or chronic cystitis. The second part of this dissertation investigates whether the sensitization that accompanies bladder inflammation can he suppressed or eliminated by intrathecal or intravesical administration of lidocaine and the effects of lidocaine treatment on NGF and BDNF protein content in the bladder, L6/S1 DRG and dorsal lumbar spinal cord. We observed that peripheral mechanical sensitization that accompanies cystitis was blocked by lidocaine administered prior to intravesical instillation of acrolein, but this effect was not observed when lidocaine was administered after initiation of cystitis. In addition, lidocaine reduced NGF and BDNF protein content within the bladder and L6/S1 DRG after acute cystitis in rats. A better understanding of the involvement of bladder afferent pathways in peripheral mechanical sensitivity associated with bladder inflammation raises the possibility of multiple targets for treatment and prevention of pain that accompanies cystitis.