Biomedical subjects

T J Ness

Publications and source records attributed to T J Ness.

At least 37 records · Page 2Linked to original sources

PubMed1999

Kappa opioid receptor agonists differentially inhibit two classes of rat spinal neurons excited by colorectal distention.

BACKGROUND & AIMS: Quantitative neurophysiological studies have identified the presence of at least 2 spinal neuronal populations (abrupt and sustained) that are excited by the noxious visceral stimulus colorectal distention. This study examined the effects of the kappa opioid receptor agonists fedotozine and U50488H on the activity of these neurons. METHODS: In decerebrate, cervical spinal cord-transected male rats, the lumbosacral spinal cord was exposed by a laminectomy. Dorsal horn neurons showing excitatory responses to colorectal distention (80 mm Hg, 20 seconds) were identified using microelectrodes. Cumulative doses of fedotozine and U50488H were administered intravenously or intrathecally, and antagonists were used. RESULTS: Intravenous fedotozine and U50488H dose-dependently inhibited the evoked activity of sustained neurons. This inhibition was partially reversed by the kappa opioid antagonist norbinaltorphimine. The same agents had insignificant effects on the evoked activity of abrupt neurons. Fedotozine inhibited spontaneous activity of both abrupt and sustained neurons. Intrathecally administered U50488H had no effect on abrupt or sustained neurons, but intrathecally administered fedotozine inhibited the evoked and spontaneous activity of both groups. CONCLUSIONS: Kappa opioid receptor agonists acting peripherally had differential effects on 2 spinal neuronal populations responsive to colorectal distention. Fedotozine had additional inhibitory effects acting within the spinal cord.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1999

The effect of spinal analgesia on visceral nociceptive neurons in caudal medulla of the rat.

UNLABELLED: A population of neurons resident in the caudal ventrolateral medulla are excited by noxious cutaneous and visceral stimuli from large portions of the body. These neurons act as monitors of ascending nociceptive information, and we hypothesized that they would be inhibited by spinally administered analgesics in a clinically relevant fashion. Rats were anesthetized with oxygen/ halothane. The caudal medulla was surgically exposed, and a catheter placed into the intrathecal space overlying the lower thoracic spinal cord via the surgical site. Single medullary neurons were characterized for responses to cutaneous and visceral (colorectal distension) stimuli. The effects of i.v. and intrathecally administered morphine and lidocaine were determined. The intrathecal infusion of morphine for 6 days before testing was also used as a pretreatment. Colorectal distension-evoked responses of medullary nociceptive neurons were inhibited in a dose-dependent, naloxonereversible fashion by intrathecal and i.v. morphine (50% effective dose values: 3.5 and 440 microg/kg, respectively). Intrathecal lidocaine abolished responses to colorectal distension and produced a spinal level at doses producing minimal effects when administered systemically. Prior treatment with an infusion of morphine produced tolerance to the effects of subsequent intrathecal morphine administration. These findings support the use of this preparation as a neurophysiologic model of spinal analgesia. IMPLICATIONS: Neurons in the brainstem, isolated electrophysiologically, were used as whole body monitors of pain-related activity in the rat. As a neurophysiologic model of nociception, this preparation may prove useful for the study of regionally administered analgesics and local anesthetics.

Analgesia↗

PubMed1998

Characterization of neurons in the area of the medullary lateral reticular nucleus responsive to noxious visceral and cutaneous stimuli.

In halothane-anesthetized rats, 283 caudal medullary neurons responsive to colorectal distension (CRD) were characterized using extracellular electrodes. Neurons inhibited by CRD (n = 82) were in the area dorsal to the lateral reticular nucleus (LRN). Most neurons excited by CRD (n = 130) were located within or immediately adjacent to the LRN, were excited by noxious heat and/or noxious pinch of at least half the body surface and were called bilateral nociceptive specific (bNS) neurons. bNS neurons had accelerating responses to graded CRD (threshold: 20 +/- 2 mmHg). Ten of twelve bNS neurons tested could be antidromically activated by electrical stimulation of the midline cerebellum. Other neurons excited by CRD (n = 71) had mixed responses to cutaneous stimuli and were generally located in the area dorsal to the LRN. Increases in blood pressure due to intravenous phenylephrine did not significantly alter the spontaneous activity of neurons excited by CRD, but altered spontaneous activity (12 excited, four inhibited) in all neurons tested which were inhibited by CRD. Decreases in blood pressure produced by intravenous nitroprusside produced a reciprocal response in most neurons inhibited by CRD and had a delayed onset (20-30 s after bolus administration) excitatory effect on 21 of 27 units excited by CRD. Combined with other studies, these data suggest a role for neurons within and adjacent to the LRN in the modulation of visceral nociception. They also implicate a role for the cerebellum in visceral nociceptive processing.

Animals↗

PubMed1998

The development of tolerance to intrathecal morphine in rat models of visceral and cutaneous pain.

The development of tolerance to intrathecal morphine was studied in rats chronically implanted with intrathecal catheters connected to osmotic minipumps. Measures of cutaneous nociception were the hot plate (HP) and tail flick (TF) tests. Measures of visceral nociception were visceromotor (VM) responses to ramped colorectal distension (CRD) and cardiovascular (CV) responses to phasic colorectal distension. Tolerance to a continuous infusion of 6 or 20 nmol/h of morphine sulfate developed over 6 days. A significant reduction in the dose-dependent effects of intrathecal morphine in the TF and HP tests and VM and CV responses to CRD occurred in rats receiving continuous infusions of morphine. The development of tolerance to intrathecal morphine was similar in both cutaneous and visceral models.

Animals↗

PubMed1998

The effect of morphine on responses of mediodorsal thalamic nuclei and nucleus submedius neurons to colorectal distension in the rat.

In halothane-anesthetized rats, we characterized the responses of single neurons in the nuclei of medial thalamus (MT), specifically the mediodorsal thalamic nucleus (MD) and the nucleus submedius (Sm), to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine (Mor) on these responses using standard extracellular microelectrode recording techniques. 62 MD and 46 Sm neurons were isolated on the basis of spontaneous activity. 47 of the MD neurons (76%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. 38 of the Sm neurons (83%) responded to CRD, of which 89% had excitatory and 11% had inhibitory responses. Responses of MD and Sm neurons excited by CRD were related significantly to distension pressure (20-100 mmHg), with maximum excitation occurring at 60 and 100 mmHg, respectively. MD neurons inhibited by CRD also had graded responses to graded CRD, with maximum inhibition occurring at 80 mmHg. The responses to noxious (pinch, heat) and nonnoxious (tap, brush) cutaneous stimuli were studied in 59 of the MD and 44 of the Sm neurons isolated. 22 of the MD neurons (37%) studied had cutaneous receptive fields, of which 59% were large and bilateral, 41% were small and usually contralateral receptive fields. 55% of these neurons were nociceptive-specific, 45% responded to both noxious and nonnoxious cutaneous stimulation. 29 of the Sm neurons (66%) studied had cutaneous receptive fields, of which 72% were large and usually bilateral, 14% were small and bilateral, 14% were small and contralateral receptive fields. 90% of these neurons were nociceptive-specific, 10% responded to both noxious and nonnoxious stimulation. No MD or Sm neurons responded exclusively to nonnoxious cutaneous stimulation. Mor (0.125, 0.25, 0.5 and 1 mg/kg I.V.) attenuated MD and Sm neuronal excitatory responses to CRD in a dose-dependent fashion, abolishing evoked activity with a dose of 0.5 mg/kg (p < 0.05) and 1 mg/kg (p < 0.05), respectively. Naloxone (0.4 mg/kg I.V.) reversed the effects of Mor. Mor and naloxone had no effects on spontaneous activity. These data support the involvement of MD and Sm neurons in visceral nociception, and are consistent with a role of Sm in affective-motivational, and MD in both sensory-discriminative and affective-motivational aspects of nociception.

Analgesics, Opioid↗

PubMed1998

A psychophysical study of discomfort produced by repeated filling of the urinary bladder.

Psychophysical studies were performed in 10 healthy, female volunteers using urinary bladder distension (UBD) as a visceral stimulus. Stimulus methodology was similar to that used clinically for obtaining cystometrograms with a fixed-rate (100 cc/min normal saline) filling of the urinary bladder, occasional pauses and simultaneous measure of bladder pressure using a catheter-transducer assembly. During bladder filling, subjects were asked to report sensations by verbal report and by using an electronic, hand-held, visual-analog-scale device. Sensations evoked by UBD were generally localized to the suprapubic region. UBD produced cardiovascular responses which increased with repeated trials. Sensation intensity increased with repeated UBDs as indicated by global pain ratings. Intravesical pressure and volume correlated with sensation intensity. The volume of distending fluid needed to produce a report of discomfort was highly variable from trial to trial and did not change significantly with repeated UBDs. The intravesical pressure which produced a report of discomfort was less variable and significantly decreased with repeated UBDs. The change in intravesical pressure and volume needed to produce discomfort was inversely correlated with initial intravesical pressure measures. Similar to findings in other organ systems, these findings demonstrate that repeated presentations of a visceral stimulus may lead to an increase in physiological and perceptual responses to pain.

Adult↗

PubMed1991

Further behavioral evidence that colorectal distension is a 'noxious' visceral stimulus in rats.

'Noxious' stimuli are pain-producing stimuli and have been traditionally defined as tissue damaging. This definition is not valid for visceral stimuli. Hence, behavioral definitions are needed. Awake, unanesthetized rats learned to passively avoid colorectal distension. The rate of acquisition increased as a function of the distending pressure. Two manipulations, intrathecal morphine and neonatal treatment with capsaicin, attenuated acquisition of avoidance behavior whereas the production of colorectal inflammation using turpentine enhanced acquisition of this behavior. These findings are consistent with the hypothesis that aversion to the stimulus is due to the 'noxious' nature of the stimulus.

Animals↗

PubMed1991

Neonatal capsaicin treatment abolishes the nociceptive responses to intravenous 5-HT in the rat.

The intravenous (i.v.) administration of serotonin (5-HT) to lightly pentobarbital-anesthetized rats is known to produce a triad of reflex cardiovascular responses, distinct afferent-mediated pseudaffective reactions, and a vagally mediated inhibition of the nociceptive tail-flick (TF) reflex consistent with 5-HT acting as a noxious stimulus. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating these responses. Lightly pentobarbital-anesthetized 16-week-old male Sprague-Dawley rats which had been treated as neonates (in the first 48 h of life) with capsaicin (50 micrograms/kg, s.c.) were compared to age-matched neonatal vehicle-treated controls. Whereas the i.v. administration of 5-HT produced a dose-dependent (6-96 micrograms/kg, i.v.) inhibition of the nociceptive TF reflex (ED50 = 48.1 +/- 11.3 micrograms/kg; n = 7) and distinct pseudaffective responses (usually by 24-48 micrograms/kg) in vehicle-treated rats, 5-HT (6-192 micrograms/kg, i.v.) failed to significantly alter TF latency or produce pseudaffective behaviors in the capsaicin-treated rats (n = 10). There was no difference in baseline TF latencies between the two groups. There were essentially no differences between vehicle- and capsaicin-treated rats with respect to the initial cardiopulmonary vagal afferent-mediated (Bezold-Jarisch reflex) decreases in heart rate and arterial blood pressure or the subsequent pressor phase. However, the magnitude of the late hypotensive phase was significantly greater in capsaicin-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Central mechanisms of visceral pain.

Deep pain arising from muscle, joints, connective tissue, and the viscera is different in character and quality from pain arising from cutaneous structures. Deep pains, particularly visceral pain, are poorly localized, typically referred or transferred to a cutaneous site, and generally produce strong emotional and autonomic responses and tonic muscle contractions. Despite the prevalence and clinical importance of deep pains, it is only relatively recently that investigative efforts have begun to focus on the mechanisms of deep pain. The present report briefly reviews the development and use of a model of visceral pain that employs constant pressure distension of the colon and rectum as a noxious stimulus. Converging behavioral, pharmacological, and physiological evidence that colorectal distension is a valid, reliable, noxious, visceral stimulus is presented.

Animals↗

PubMed1991

Interactions between visceral and cutaneous nociception in the rat. I. Noxious cutaneous stimuli inhibit visceral nociceptive neurons and reflexes.

1. Numerous studies have demonstrated that neural, behavioral, and reflex responses to a nociceptive test stimulus are inhibited by conditioning nociceptive stimuli; this inhibition has supraspinal, intraspinal, and segmental components. The general phenomenon is defined here as nocigenic inhibition. The present study of nocigenic inhibition documents that noxious cutaneous pinch and heat, used as conditioning stimuli, inhibit neuronal and reflex responses evoked by a noxious visceral stimulus, colorectal distension. 2. A total of 196 dorsal horn neurons were examined: 110 were short latency-abrupt (SL-A) neurons that were excited at short latency by colorectal distension and returned to baseline activity abruptly after termination of the distending stimulus, and 86 were short latency-sustained (SL-S) neurons that also were excited by colorectal distension at short latency, but demonstrated after-discharges for 4-240 s after termination of the distending stimulus. All SL-A and SL-S neurons studied had convergent cutaneous receptive fields. 3. The spontaneous activities of 100% of the 110 SL-A neurons tested were inhibited by greater than 25% by noxious pinch in sites distant from their convergent cutaneous receptive fields. In both anesthetized, intact, and spinalized rats, noxious conditioning pinch or noxious conditioning heat significantly reduced responses of SL-A neurons during noxious test colorectal distension. The magnitude of this nocigenic inhibition was graded with the intensity of the noxious conditioning stimulus. Noxious conditioning tail heating produced a parallel shift to the right in stimulus-response functions relating neuronal responses to the intensity of colorectal distension (20-100 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Interactions between visceral and cutaneous nociception in the rat. II. Noxious visceral stimuli inhibit cutaneous nociceptive neurons and reflexes.

1. Nocigenic inhibition is the inhibition of neural, behavioral, or reflex responses to a nociceptive test stimulus produced by another, conditioning, nociceptive stimulus. The present study examines whether a natural noxious visceral stimulus, colorectal distension, used as a conditioning stimulus would inhibit neuronal or reflex responses to noxious cutaneous stimuli. Segmental effects of colorectal distension have been previously characterized; hence conditioning effects of colorectal distension on stimuli applied at sites distant (heterosegmental effects) and adjacent (perisegmental effects) to those areas of the spinal cord that receive the greatest afferent input from the colon were examined. The conditioning effects of colorectal distension were compared with those of noxious pinch. 2. Heterosegmental effects of colorectal distension were studied in 129 neurons located in the area of the trigeminal nucleus caudalis and cervical spinal dorsal horn. Steady-state activity (spontaneous activity or activity evoked by sustained pressure) of 106 of 129 trigeminal-cervical dorsal horn neurons was inhibited by both noxious colorectal distension (100 mmHg, 20 s) and noxious pinch of the tail; all neurons inhibited by colorectal distension were also inhibited by noxious pinch. Inhibition was graded with the intensity of the distending stimulus. The class 2-class 3 classification system (neurons excited by nonnoxious and noxious or only by noxious cutaneous stimuli, respectively) was roughly predictive of susceptibility to nocigenic inhibition, because 74 of 75 class 2 neurons tested were inhibited by noxious colorectal distension or noxious pinch and only 32 of 54 class 3 neurons were similarly inhibited. Five neurons were excited by colorectal distension, all of which were class 3 neurons. 3. Perisegmental effects of colorectal distension were observed in 100 L3-L5 spinal dorsal horn neurons. The spontaneous activities and responses during noxious test heating of the glabrous skin of the hindpaw of these neurons were affected in the same way by noxious (conditioning) colorectal distension. All neurons inhibited by colorectal distension (51 class 2 and 8 class 3 neurons) were also inhibited by noxious pinch of the nose or forepaw. The magnitude of the nocigenic inhibition of responses during heating of the hindpaw was graded with the intensity and duration of the noxious conditioning colorectal distension, was a function of the number of preceding distensions given to the rat, and outlasted the distending stimulus. Conditioning colorectal distension also produced a parallel shift to the right in stimulus-response functions relating responses of neurons to the intensity of the noxious test stimulus (42-50 degrees C).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Vagal afferent-mediated inhibition of a nociceptive reflex by intravenous serotonin in the rat. I. Characterization.

The effect of intravenous (i.v.) serotonin (5-HT) on nociception and blood pressure was examined in male Sprague-Dawley rats. Intravenous 5-HT produced a dose-dependent (6-192 micrograms/kg, i.v.) inhibition of the nociceptive tail-flick (TF) reflex in lightly pentobarbital-anesthetized (ED50 = 40 micrograms/kg) and conscious rats (ED50 = 44 micrograms/kg). In the lightly pentobarbital-anesthetized rat, the blood pressure response to i.v. 5-HT was typically a triphasic response with a marked Bezold-Jarisch reflex-induced decrease in pressure (associated with a brief period of apnea) followed by a pressor phase and a subsequent delayed hypotension. In the conscious rat, the response was typically biphasic with the late hypotensive phase absent. A variety of anatomical and pharmacological manipulations were performed to characterize the 5-HT-induced inhibition of the TF reflex and associated changes in blood pressure. Prevention of 5-HT-induced reflex apnea by artificial ventilation did not affect inhibition of the TF reflex produced by 5-HT. Pharmacological manipulations were performed to mimic, as closely as possible, the acute increases and decreases in blood pressure associated with i.v. 5-HT. Nitroprusside (8 micrograms/kg, i.v.) produced a decrease in blood pressure of similar magnitude and rate as that associated with the Bezold-Jarisch reflex-induced decrease in pressure produced by 72 micrograms/kg 5-HT, but did not change TF latency from baseline. Similarly, acute increases in pressure produced by phenylephrine (8 micrograms/kg, i.v.), intended to mimic the secondary pressor effect of 5-HT, did not change TF latency. The short-acting ganglion blocker trimethaphan (5 mg/kg, i.v.) closely mimicked the late hypotensive phase produced by 5-HT, but again resulted in no change in TF latency. Pretreatment with the ganglion blocker chlorisondamine (2.5 mg/kg) abolished all depressor responses to 72 micrograms/kg 5-HT, but did not significantly affect the TF reflex. These results indicate that acute changes in blood pressure and respiration associated with i.v. 5-HT do not contribute to inhibition of the TF reflex. This conclusion was confirmed in experiments in which bilateral vagotomy abolished approximately 70% of the 5-HT-induced inhibition of the TF reflex (and all depressor responses), and resulted in a significantly greater pressor response. Finally, low thoracic spinal cord transection (T9-10) abolished the inhibition of the TF reflex produced by i.v. 5-HT. Therefore, 5-HT stimulates vagal afferents and inhibits the TF reflex by activating descending inhibitory systems from the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1990

Visceral pain: a review of experimental studies.

This paper reviews clinical and basic science research reports and is directed toward an understanding of visceral pain, with emphasis on studies related to spinal processing. Four main types of visceral stimuli have been employed in experimental studies of visceral nociception: (1) electrical, (2) mechanical, (3) ischemic, and (4) chemical. Studies of visceral pain are discussed in relation to the use and 'adequacy' of these stimuli and the responses produced (e.g., behavioral, pseudoaffective, neuronal, etc.). We propose a definition of an adequate noxious visceral stimulus and speculate on spinal mechanisms of visceral pain.

Abdominal Pain↗

PubMed1990

A psychophysiological study in humans using phasic colonic distension as a noxious visceral stimulus.

Psychophysiological experiments were performed in 9 humans using constant-pressure, phasic, graded distention (30 sec, 20-70 mm Hg) of the sigmoid colon as a visceral stimulus. Reliable cardiovascular (pressor), respiratory and visceromotor responses in addition to reports of pressure/pain sensations were evoked by colonic distension in 8 of the 9 subjects. The pressure/pain sensations were referred to the lower abdomen, lower back and perineum and their intensity quantified using a visual analogue scale. Responses to colonic distension were graded and increased with repeated distensions at the same intensity (60 mm Hg). The area of referral as indicated by subject drawings increased with repeated distensions as did the intensity of the subjects' sensory and affective descriptors of the sensation. Five of the subjects differentiated between 'pressure' and 'pain' sensations evoked by colonic distension; the intensity of the 'pain' sensation accelerated during the distending stimulus whereas the 'pressure' sensation was typically stable or adapting during the distending stimulus.

Adult↗

PubMed1989

Characterization of superficial T13-L2 dorsal horn neurons encoding for colorectal distension in the rat: comparison with neurons in deep laminae.

Fifty-five neurons responsive to colorectal distension located in the superficial spinal dorsal horn (0.0-0.3 mm ventral to the cord dorsum) of the T13-L2 spinal segments of pentobarbital-anesthetized, physiologically intact or spinalized (C1 transection), decerebrate rats were characterized. These neurons could be separated into three groups based upon their response to an 80 mm Hg, 20 s colorectal distension: (1) short latency-abrupt (SL-A) neurons (n = 22) that were excited by colorectal distension at a short latency (less than 1 s) and abruptly terminated responses following the termination of the distending stimulus; (2) short latency-sustained (SL-S) neurons (n = 26) that were excited by colorectal distension at a short latency (less than 1 s) and demonstrated sustained responses (greater than 4 s) following termination of the distending stimulus; and (3) INHIB neurons (n = 7) that were spontaneously active and were inhibited by colorectal distension. All 55 neurons had convergent cutaneous receptive fields (i.e. were 'viscerosomatic'), exhibiting excitatory responses to noxious (pinch/heat) and/or non-noxious (brush) stimuli. Neurons excited by colorectal distension also demonstrated monotonic, accelerating responses to graded colorectal distension, were excited by the intraarterial administration of bradykinin, could be antidromically activated by electrical stimulation in the caudal ventrolateral medulla and were subject to tonic descending inhibitory modulation as evidenced by more vigorous responses to distension when rats were reversibly spinalized using a cold block.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Differential effects of morphine and clonidine on visceral and cutaneous spinal nociceptive transmission in the rat.

1. The effect of morphine or clonidine administered systemically on visceral and cutaneous spinal nociceptive transmission was examined in 45 dorsal horn neurons in spinalized, decerebrate rats: 17 "cutaneous" dorsal horn neurons located in the L3-L5 spinal segments were excited by heating the glabrous skin of the hindpaw (48 degrees C, 15 s) and 28 "visceral" dorsal horn neurons located in the T13-L2 spinal segments were excited by colorectal distension (80 mmHg, 20 s). The 28 visceral dorsal horn neurons were subclassified as 18 short-latency abrupt neurons (SL-A), which were excited by colorectal distension at short latency (less than 1 s) and whose activity abruptly returned to base line following termination of the distending stimulus, and as 10 short-latency-sustained (SL-S) neurons, which also were excited at short latency (less than 1 s) by colorectal distension, but whose activity was sustained above base line for 4-31 s following termination of the distending stimulus. 2. Morphine produced a dose-dependent, naloxone-reversible inhibition of both spontaneous activity and/or neuronal responses during heating or colorectal distension of 8 SL-A, 7 SL-S, and 11 cutaneous dorsal horn neurons. Comparison of the effective doses of morphine to produce a 50% reduction in the response of the neurons (ED50s) during colorectal distension or heating demonstrated that, at the intensities of distension and heating employed, SL-S neurons were affected at the least dosage (ED50 = 0.46 mumol/kg), followed by SL-A neurons (ED50 = 1.95 mumol/kg) and cutaneous neurons (ED50 = 6.12 mumol/kg). Effects on spontaneous activity were variable: at low doses morphine produced an increase in the spontaneous activity of 2 SL-A and 5 cutaneous neurons; greater doses (up to 42 mumol/kg) inhibited in all of the SL-A and SL-S neurons, but not three cutaneous neurons studied. With the exclusion of these three neurons, the ED50s for inhibition of spontaneous activity were comparable to the ED50s for inhibition of neuronal responses during colorectal distension or heating of the hindpaw in all three neuronal groups. 3. Clonidine produced a dose-dependent, yohimbine- or phentolamine-reversible inhibition of both spontaneous activity and neuronal responses during heating or colorectal distension of 10 SL-A, 3 SL-S, and 6 cutaneous dorsal horn neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudaffective reflexes in the rat.

This report presents evidence that colorectal distension is a reproducible, reliable, valid, noxious visceral stimulus that can be used in studies performed in awake, unanesthetized, unrestrained rats. Colorectal distension produces aversive behavior and cardiovascular and visceromotor responses which are quantifiable, reliable, reproducible and useful for inter- and intra-animal studies. The cardiovascular response, a pressor response with tachycardia, is graded and thought to be due to an increase in sympathetic outflow coupled with removal of vagal tone since it is attenuated in a dose-dependent way by atropine, propranolol, phentolamine, chlorisondamine and adrenal demedullation. The visceromotor response is a contraction of abdominal and hindlimb musculature. The distending pressure threshold for the visceromotor response (22.4 +/- 0.9 mm Hg) is significantly greater than that necessary to evoke a non-nociceptive response, relaxation of the anal sphincters (13.2 +/- 0.7 mm Hg). Both the cardiovascular and visceromotor responses act via brainstem loops since both are vigorous in decerebrate (midcollicular) but not spinalized (C1 or T6) rats. Anesthetics attenuated (alphaxalone/alphadolone, ketamine) or reversed (urethane, pentobarbital, alpha-chloralose) the cardiovascular responses to colorectal distension and attenuated (alphaxalone/alphadolone) or abolished (others listed above) the visceromotor response. Both morphine (systemic and intrathecal) and clonidine (intrathecal) produced a dose-dependent inhibition of both the cardiovascular and visceromotor responses to colorectal distension. Thus, in the awake, unrestrained rat, the cardiovascular and visceromotor responses to colorectal distension are quantifiable, reliable and reproducible signs of acute visceral nociception.

Anesthetics↗

PubMed1988

Characterization of neurons responsive to noxious colorectal distension in the T13-L2 spinal cord of the rat.

1. One-hundred thirty-two neurons responsive to colorectal distension in the dorsal horn of the T13-L2 spinal segments of 35 spinalized and 7 intact, deeply pentobarbital-sodium-anesthetized rats were characterized for convergent cutaneous receptive fields, long ascending projections and responses to the intra-arterial administration of the algesic peptide bradykinin. All but 9 neurons had an identifiable excitatory cutaneous receptive field; all receptive fields were located on the lower abdomen, flank, and dorsal body surface. Electrical stimulation in the cutaneous fields of 28 neurons demonstrated that neurons responsive to colorectal distension receive afferent information carried by A- and C-fibers. Stimulus-response functions (SRFs) of 52 neurons excited by graded colorectal distension (20-100 mmHg, 20 s) were monotonic and accelerating, allowing extrapolation of threshold distending pressures to neuronal response. Neurons were subdivided into four classes based upon their response to an 80-mmHg, 20-s colorectal distension search stimulus. 2. Short-latency abrupt [SL-A] neurons (spinalized, n = 46; intact, n = 9) were excited at short latency; activity abruptly returned to base line on termination of distension. Six of 9 neurons in intact rats had long ascending projections as demonstrated by antidromic invasion from the contralateral, ventrolateral caudal medulla. Responses of SL-A neurons to colorectal distension were significantly greater in spinalized than in intact rats. Fifty-three of 55 SL-A neurons had convergent excitatory cutaneous receptive fields and most were responsive to both noxious and nonnoxious stimuli. Ten of 13 neurons tested were excited by intra-arterial bradykinin. The threshold distending pressure, determined from the SRFs of 29 neurons in both the spinalized and intact states, extrapolated to near 0 mmHg. 3. Short-latency sustained (SL-S) neurons (spinalized, n = 31; intact, n = 11) were also excited at short latency in response to colorectal distension, but responses were sustained for 4-50 s following termination of the distending stimulus. Nine of 11 SL-S neurons in intact rats had long ascending projections. All 42 SL-S neurons were spontaneously active and 41 of 42 had convergent excitatory cutaneous receptive fields, excited exclusively by noxious stimuli (n = 29) or excited by both noxious and nonnoxious stimuli (n = 12). Responses to colorectal distension and spontaneous activity were significantly greater in spinalized rats. Twelve of 12 neurons tested were excited by intra-arterial bradykinin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗