1. Single-unit activity was recorded from S1 dorsal root afferent fibers in pentobarbital-anesthetized rats. In 25 experiments, 245 afferent fibers were identified by electrical stimulation of the pelvic nerve. Fifty-two percent were C fibers (conduction velocity: 1.70 +/- 0.04 m/s; mean +/- SE) and 48% were A delta-fibers (conduction velocity: 11.07 +/- 0.95 m/s). 2. Of 245 pelvic nerve afferent fibers, 92 (38%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 57 of these fibers were C fibers and 35 were A delta-fibers. Forty-four fibers responded to colorectal distension (CRD; 80 mmHg); 32 were C fibers and 12 were A delta-fibers. A total of 39 fibers were identified in the anal mucosa; 3 were C fibers and 36 were A delta-fibers. Seventy fibers (28%) in these experiments were unresponsive to either UBD or CRD or to probing of the anal mucosa; 32 were unmyelinated C fibers and 38 were A delta-fibers. 3. Reproducibility of responses to repeated UBD (80 mmHg, 20 s; 8 trials at 4-min intervals) was tested in 10 fibers. In nine fibers, responses to repeated distension did not change; one fiber exhibited a progressive decrease in response magnitude after the third trial. 4. Of the 92 afferent fibers that responded to UBD, 45 were further characterized for responses to graded intensities of UBD. Forty fibers had some resting activity (1.7 +/- 0.3 impulses/s) and five fibers exhibited no ongoing activity. The response to UBD adapted slowly during the 20-s period of phasic UBD or during slow isotonic filling of the bladder. 5. The stimulus-response function (SRF) of fibers (n = 45) to graded UBD was monotonic < or = 80 mmHg. Thresholds for responses were determined after extrapolation of the least-squares linear regression line to the ordinate, and varied between 0 and 45 mmHg. The frequency distribution profile of thresholds revealed two populations of pelvic nerve afferent fibers in the urinary bladder: a larger group (n = 36) of low-threshold (LT) fibers (5.7 +/- 1.0 mmHg) and a smaller group (n = 9) of high-threshold (HT) fibers (34 +/- 2.5 mmHg). 6. Responses of four LT fibers to graded UBD were tested before and 30 min after instillation of 0.5 ml of 0.5% acetic acid (pH 3) into the bladder. The mean threshold for response of these fibers before instillation of acetic acid (9.4 +/- 3.1 mmHg) more than doubled (to 22.3 +/- 6.7 mmHg) after instillation of acetic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Single-unit activity was recorded from S1 sacral dorsal root afferent fibers in the anesthetized rat. A total of 364 afferent fibers were identified by electrical stimulation of the pelvic nerve and subsequently tested for response to colorectal distension (CRD) and urinary bladder distension (UBD). Sixty-seven percent (n = 244) of the fibers were unmyelinated C-fibers and 33% (n = 120) were thinly myelinated A delta-fibers. 2. In three initial experiments, 35 fibers were identified by pelvic nerve stimulation and tested for response only to CRD; none of these fibers responded to CRD. In 20 subsequent experiments, 329 pelvic nerve afferent fibers were tested for response to CRD and UBD. Thirty-four percent (n = 112) of the 329 fibers were unresponsive to noxious CRD (80 mmHg) or to UBD (slow filling< or = 100 mmHg), 44% (n = 146) responded to UBD, 16% (n = 53) responded to CRD, and 6% (n = 18) responded to mechanical stimulation of the anal mucosa. 3. Of the total of 53 pelvic nerve afferent fibers that responded to CRD, 43 (81%) were C-fibers (mean: 1.5 m/s) and 10 (19%) were A delta-fibers (mean: 4.7 m/s). Fifteen of the CRD-sensitive fibers had no resting activity, whereas 38 fibers exhibited some resting activity (mean: 2.6 imp/s). 4. Reproducibility of responses to repeated CRD (80 mmHg, 30s, 10 trials at 4-min intervals) was tested in 17 fibers. In 16, responses to repeated distension were reproducible without evidence of facilitation or inhibition of subsequent responses. One fiber gave greater responses during the 9th and 10th trials. 5. Responses to graded CRD were studied in 44 fibers. All fibers exhibited monotonic, increasing stimulus-response functions < or = 80 mmHg of distension. Thresholds for response of the 44 fibers were determined after extrapolation of the least-squares linear-regression line to the ordinate and varied between 0 and 40 mmHg. Two populations of pelvic nerve afferent fibers in the colon were apparent: low threshold (LT) afferent fibers had a mean threshold of 2.9 mmHg (range: 0-10 mmHg; n = 34) and high threshold (HT) afferent fibers had a mean threshold of 32.6 mmHg (range: 28.0-40.0 mmHg; n = 10). 6. Chemosensitivity to bradykinin (BK) was tested in nine LT fibers. Seven fibers responded to BK (0.1 to 100 micrograms/kg ia) and two fibers did not respond up to 100 micrograms/kg of BK. Responses to BK tested in three fibers were dose dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

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The objective of this study was to examine the antinociceptive effects of peripherally restricted kappa-opioid receptor agonists (ORAs) in a rat model of inflammatory bowel disease produced by intracolonic instillation of trinitrobenzine sulfonic acid (TNBS). Antinociceptive effects of mu-(morphine) and kappa-ORAs (EMD 61,753 and ICI 204,488) were evaluated in a behavioral model of visceral nociception. The effects of these agonists and a delta-ORA (SNC 80) on responses of pelvic nerve afferent fibers innervating the colon were also tested. In the behavioral study, systemic injections of morphine and both kappa-ORAs dose-dependently inhibited the visceromotor response to colorectal distension in rats with uninflamed or inflamed colons. The inhibitory effects of kappa-ORAs, but not morphine, were significantly greater in rats with colons inflamed 4 days previously by TNBS. A mu-receptor-selective dose (30 microg/kg) of naloxone methiodide (NLXM) blocked the inhibitory effect of morphine, but not of EMD 61,753. In the single-fiber study, neither morphine nor the delta-ORA SNC 80 attenuated the responses of pelvic nerve afferent fibers, whereas kappa-ORAs dose-dependently inhibited responses of pelvic nerve afferent fibers with significantly greater potency in the inflamed colon. Pretreatment with a non-opioid receptor-selective dose (2 mg/kg) of NLXM produced a rightward shift in the dose-response function of EMD 61,753. The greater potency of kappa-ORAs in the TNBS-inflamed condition suggests a peripheral upregulation of kappa-opioid receptors in colonic inflammation.