MP12-01 SPINAL METABOTROPIC GLUTAMATE RECEPTOR 5 INVOLVEMENT IN PUDENDAL INHIBITION OF NOCICEPTIVE BLADDER REFLEX IN CATS

INTRODUCTION AND OBJECTIVES: Spinal cord transection (SCT) results in disruption of the Ad-fiber mediated supraspinal voiding reflex with emergence of a C-fiber mediated spinal reflex. Pudendal nerve stimulation (PNS) can increase bladder capacity and reduce storage pressures in both acute and chronic spinal cord injury models. Metabotropic glutamate receptor 5 (mGluR5) is widely expressed in the CNS and has been shown to suppress excitatory transmission of the micturition reflex. This study investigates the role and location of mGluR5 in pudendal nerve inhibition of C-fiber mediated spinal bladder reflex using an acute SCT model. METHODS: Cystometrograms (CMGs) were performed on 12 cats under a-chloralose anesthesia. Saline control capacity was establish followed by acute SCT at T9/T10. CMGs were performed using 0.25% acetic acid (AA) to activate nociceptive C-fiber bladder afferents and induce spinal bladder reflexes. PNS was applied at 5 Hz at 2 and 4 times the threshold (T) for inducing anal twitch. Under isovolumetric conditions, MTEP (a selective mGluR5 antagonist) was given (3 mg/kg, i.v.) to determine its effect on PNS. Six of the cats were treated with propranolol (3 mg/kg, i.v.) prior to MTEP administration. Hexamethonium (10 mg/kg, i.v.) was given at the end of each experiment to block the spinal bladder reflex. RESULTS: Following T9/T10 SCT and AA irritation, CMGs showed a spinal bladder reflex resulting in low amplitude (<50 cmH2O), short duration (<30 s) contractions at a significantly lower bladder volume 78.69% 26.2% of saline control capacity. During AA irritation, MTEP resulted in a significant increase in control capacity from 71.77% 24.17% to 93.97 34.05% but did not significantly change maximal contraction amplitude. MTEP given after propranolol resulted in significantly reduced contraction amplitude from 18.57 5.2 to 6.62 3.0 cmH2O and significantly increased capacity from 56.91 25.8% to 78.53 31.94%. MTEP resulted in elimination of PNS inhibition at both 2T and 4T stimulation without changing the control capacity. Propranolol did not fully remove PNS inhibition, but MTEP after propranolol treatment completely eliminated the PNS inhibition. CONCLUSIONS: Our study reveals the presence of mGluR5 in the nociceptive C-fiber mediated spinal bladder reflex and substantiates the role of spinal mGluR5 in PNS inhibition of the nociceptive C-fiber mediated bladder reflex. Understanding of the location and neurotransmitters involved in PNS may help to create new therapies for overactive bladder.