Previous studies have shown that spinal cord stimulation (SCS) of upper lumbar segments decreases visceromotor responses to mechanical stimuli in a sensitized rat colon and reduces symptoms of irritable bowel syndrome in patients. SCS applied to the upper cervical spinal dorsal column reduces pain of chronic refractory angina. Further, chemical stimulation of C1-C2 propriospinal neurons in rats modulates the responses of lumbosacral spinal neurons to colorectal distension. The present study was designed to compare the effects of upper cervical and lumbar SCS on activity of lumbosacral neurons receiving noxious colorectal input. Extracellular potentials of L6-S2 spinal neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. SCS (50 Hz, 0.2 ms) at low intensity (90% of motor threshold) was applied to the dorsal column of upper cervical (C1-C2) or upper lumbar (L2-L3) ipsilateral spinal segments. Colorectal distension (CRD, 20, 40, 60 mmHg, 20 s) was produced by air inflation of a latex balloon. Results showed that SCS applied to L2-L3 and C1-C2 segments significantly reduced the excitatory responses to noxious CRD from 417.6±68.0 imp to 296.3±53.6 imp (P<0.05, n=24) and from 336.2±64.5 imp to 225.0±73.3 imp (P<0.05, n= 18), respectively. Effects of L2-L3 and C1-C2 SCS lasted 10.2±1.9 min and 8.0 ±0.9 min after offset of CRD. Effects of SCS were observed on spinal neurons with either high or low threshold excitatory responses to CRD. However, L2-L3 or C1-C2 SCS did not significantly affect inhibitory neuronal responses to CRD. C1-C2 SCS-induced effects were abolished by cutting the C7-C8 dorsal column but not by spinal transection at cervicomedullary junction. These data demonstrated that upper cervical or lumbar SCS modulated responses of lumbosacral spinal neurons to noxious mechanical stimulation of the colon, thereby, proved two loci for a potential therapeutic effect of SCS in patients with irritable bowel syndrome and other colonic disorders.