Biomedical subjects

A Randich

Publications and source records attributed to A Randich.

At least 37 records · Page 2Linked to original sources

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

Antinociception and cardiovascular responses produced by intravenous morphine: the role of vagal afferents.

The mechanisms of the antinociceptive, depressor and bradycardic responses produced by intravenous (i.v.) administration of morphine were examined in rats lightly anesthetized with pentobarbital sodium. Intravenous administration of 0.1, 0.25, 0.5, 1.0 or 2.5 mg/kg of morphine produced dose-dependent inhibition of the nociceptive tail flick (TF) reflex, hypotension, and bradycardia. Bilateral cervical vagotomy (CVAG) significantly attenuated the antinociception produced by i.v. morphine and the degree of attenuation was inversely related to drug dose. CVAG had no effect on the depressor response produced by lesser doses of morphine (0.1 or 0.5 mg/kg), but at greater doses converted the depressor response into either a pressor response (1.0 mg/kg) or an initial pressor response followed by a depressor response (2.5 mg/kg). Morphine-induced bradycardia was blocked by CVAG at all drug doses tested (0.1, 0.5, 1.0 and 2.5 mg/kg). In selective tests of either 0.5 or 2.5 mg/kg of i.v. morphine, prior administration of the peripherally acting opioid receptor antagonist naloxone methobromide (NMB) attenuated the antinociception to the same degree as CVAG. NMB also completely blocked the depressor and bradycardic responses of these doses of morphine. Bilateral subdiaphragmatic vagotomy (SDVAG) resulted in a marginal attenuation of antinociception at 0.5 mg/kg but not 2.5 mg/kg of morphine, and the attenuation produced by SDVAG was delayed in onset following morphine administration relative to that produced by CVAG. Bilateral sino-aortic deafferentation (SAD) had no significant effect on the antinociception in tests with 0.5 mg/kg of morphine. SDVAG and SAD had little effect on cardiovascular responses produced by these doses of morphine. The spinal antinociceptive systems activated by vagal afferents following i.v. morphine administration were characterized with the 0.5 mg/kg dose. Spinal cold block significantly antagonized the antinociception, hypotension and bradycardia produced by this dose of morphine. Intrathecal administration of naloxone (1.5, 15 or 30 micrograms) significantly antagonized the antinociception compared to saline controls, whereas intrathecal administration of methysergide (30 micrograms), phentolamine (30 micrograms), or the combination of methysergide with phentolamine (30 micrograms each) had no significant effect on the antinociception. These intrathecal doses of naloxone also antagonized the depressor and bradycardic responses produced by morphine. However, the antagonism produced by 1.5 micrograms of intrathecal naloxone was not due to spread to the systemic circulation, since i.v. administration of 1.5 micrograms of naloxone did not significantly affect either the antinociceptive or cardiovascular responses produced by morphine. These findings indicate that vagal afferents play a significant role in the antinociception produced by i.v. administration of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)

Analgesics↗

PubMed1991

Antinociception produced by electrical stimulation of vagal afferents: independence of cervical and subdiaphragmatic branches.

Expt. 1 showed that electrical stimulation of either the main dorsal or ventral branch of the subdiaphragmatic vagus could produce inhibition of the nociceptive tail-flick reflex in lightly anesthetized rats. The antinociception produced by electrical stimulation of the dorsal subdiaphragmatic vagus was eliminated by resection of the right cervical vagus, but relatively unaffected by resection of the left cervical vagus. The opposite effects for cervical vagal resection were obtained with electrical stimulation of the ventral branch of the subdiaphragmatic vagus. These results indicate that the antinociceptive effects of subdiaphragmatic vagal stimulation are mediated via uncrossed afferents traveling in the cervical vagus to activate an inhibitory spinopetal system. These findings are consistent with the established anatomy of vagal afferents. Expt. 2 showed that degeneration of the dorsal subdiaphragmatic vagus did not alter the threshold intensity of right cervical vagal stimulation necessary to produce inhibition of the tail-flick reflex. These results demonstrate that the antinociceptive effects of cervical vagal stimulation are primarily due to activation of the cardiopulmonary component of the nerve, rather than the subdiaphragmatic component. The second experiment also demonstrated that the subdiaphragmatic branch of the vagus can be selectively degenerated with ricin while leaving the cervical branch intact, even though the cell bodies of both sets of afferents are located within the nodose ganglion. These data are discussed in terms of vagal afferents and their role in the modulation of nociceptive transmission.

Animals↗

PubMed1991

Indices of stress in rats: effects of sex, perinatal alcohol and artificial rearing.

Three groups of rats were normally reared by dams, artificially reared but not exposed to alcohol or artificially reared and exposed to 6.6 g/kg/day of ethanol condensed into 8 h of each 24-h period. Alcohol exposure was given from postnatal day 4 through 9 and artificial rearing was conducted from postnatal day 4 to 12. In adulthood, approximately half of the rats were fitted with a chronic jugular catheter and were exposed to swim stress for 1 min in 21 degrees C water. Alcohol exposure augmented the corticosteroid stress response to the swim stress in female rats but not in male rats. The other half of the animals were tested for acquisition and extinction of a conditioned emotional response (CER). While alcohol exposure had no effects on the CER, extinction of CER was greatly accelerated by artificial rearing alone in female rats but not in male rats. Taken together, these findings suggest that some aspects of the stress response in female rats are more vulnerable to insults during the early postnatal period than those in male rats and that the insult-induced alterations can affect hormonal and behavioral measures differentially.

Adrenal Cortex Hormones↗

PubMed1991

Spinal serotonergic and kappa opioid receptors mediate facilitation of the tail flick reflex produced by vagal afferent stimulation.

Facilitation of the nociceptive tail flick (TF) reflex produced by low intensity (2.0 msec, 20 Hz) electrical stimulation of cervical vagal afferents (VAS) was studied in rats lightly anesthetized with pentobarbital. Serotonin (methysergide, LY 53857 or ICS 205-930), adrenergic (prazosin or yohimbine) or opioid (naloxone, nor-binaltorphimine or naltrindole) receptor antagonists were administered into the subarachnoid space of the lumbar enlargement to characterize the spinal receptors mediating VAS-produced facilitation. Spinal 5-HT1 and kappa-opioid receptors were determined to be involved in facilitation of the TF reflex produced by VAS, suggesting that facilitation of spinal nociceptive transmission by activation of cervical vagal afferents is mediated by subtypes of spinal serotonergic and opioid receptors.

Animals↗

PubMed1991

Effects of electrical stimulation of vagal afferents on spinothalamic tract cells in the rat.

The effects of electrical stimulation of cervical vagal afferents (VAS) on the background activity and on the responses of 25 spinothalamic tract (STT) neurons to noxious stimuli were studied in anesthetized rats. Background (spontaneous) activity of 9 (36%) STT neurons was inhibited by all intensities of VAS. 6 (24%) units were facilitated at lesser and inhibited at greater intensities of VAS, 5 (20%) units were only facilitated by all intensities of VAS, and 5 (20%) units were not affected by VAS. Responses of 8 (36%) STT neurons to noxious stimuli were only inhibited by VAS, 9 (41%) were facilitated at lesser and inhibited at greater intensities of VAS, and 5 units (23%) were only facilitated by VAS. There were no significant differences in VAS-produced modulatory effects between STT neurons and 16 unidentified lumbar spinal dorsal horn neurons studied under the same conditions. These results reveal that descending facilitatory and inhibitory pathways engaged by activation of vagal afferents modulate rostrally projecting nociceptive transmission neurons in the spinal cord, constituting an important regulatory network for nociception.

Anesthesia↗

PubMed1990

Acute increases in arterial blood pressure produced by occlusion of the abdominal aorta induces antinociception: peripheral and central substrates.

Occlusion of the abdominal aorta proximal to the renal arteries results in an increase in arterial blood pressure, inhibition of forepaw and hindpaw withdrawal to a noxious mechanical stimulus, and inhibition of the tail-flick reflex to noxious heat. Occlusion of the abdominal aorta distal to the renal arteries does not elevate arterial blood pressure and produces no antinociceptive effects. Occlusion of the vena cava lowers arterial blood pressure and produces no antinociception. The inhibitory effects of occlusion of the abdominal aorta depend upon activation of high pressure baroreceptors since bilateral sinoaortic denervation, but not bilateral vagotomy, eliminates the inhibition with respect to all behavioral measures. The inhibitory effects with respect to the tail-flick reflex also depend upon activation of a descending inhibitory system since reversible cold block of the spinal cord at the level of the second thoracic vertebra eliminates the antinociception. This antinociception is also eliminated following intrathecal administration of the noradrenergic receptor antagonist phentolamine, but not by intrathecal administration of either methysergide or naloxone. These data support the view that activation of high pressure baroreceptors by increases in arterial blood pressure produces antinociception via activation of a spinopetal noradrenergic system.

Animals↗

PubMed1990

Modulation of spinal nociceptive transmission from nuclei tractus solitarii: a relay for effects of vagal afferent stimulation.

1. The effects of electrical and chemical stimulation in the nucleus tractus solitarii (NTS) on spinal nociceptive transmission were examined in pentobarbital sodium-anesthetized, paralyzed rats. These studies also examined the role of the NTS as a relay for the effects of vagal afferent stimulation (VAS) on spinal nociceptive transmission. All 75 neurons studied were located in laminae I-VI in the L3-L5 spinal segments, with receptive fields on the glabrous skin of the plantar surface of the ipsilateral hindpaw. The units responded to mechanical (low and/or high intensities) and thermal stimuli (42-52 degrees C). 2. Electrical stimulation in the NTS either ipsilateral or contralateral to the spinal unit inhibited neuronal responses to noxious thermal stimuli. The magnitude of inhibition did not significantly differ as a function of either ipsilateral (15 units) or contralateral (12 units) NTS stimulation (NTSS) as indicated by extrapolated thresholds for inhibition of responses to heat, intensities to produce 50% inhibition of responses to heat, and the slope of recruitment lines for inhibition. Tracking experiments also revealed that stimulation in the area ventral to the NTS produced a greater magnitude of inhibition of these units than did NTSS. 3. NTSS significantly decreased the slope of the stimulus-response functions (SRFs) of dorsal horn units to graded thermal stimuli (42-52 degrees C), whereas response threshold was unaffected by NTSS. The apparent latency of NTSS to produce inhibition of unit responses to heating of the hindpaw was determined to be 50 +/- 10 ms (mean +/- SE). 4. Microinjection of 50 nmol of glutamate into the NTS ipsilateral to the spinal unit also inhibited neuronal responses to thermal stimuli in 17/21 units; responses of 2/21 units were facilitated. Inhibition typically lasted 4-7 min and was shown to be dose-volume dependent. 5. The effects of VAS and NTSS on spinal nociceptive transmission were directly compared. The responses of 17 units to 50 degrees C heating of the hindpaw were facilitated by low and inhibited by greater intensities of VAS (Biphasic units); the responses of 12 units were only inhibited by VAS (Inhib units); three were only facilitated (Facil units), and 2 were unaffected by VAS. In contrast, NTSS generally inhibited the same spinal units, although modest facilitation was produced by NTSS contralateral to the recording site. NTSS produced greater inhibition of the Biphasic units than did VAS, shown by a leftward shift of the recruitment line of inhibition and greater inhibition at the same intensity of electrical stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1990

Electrical stimulation of cervical vagal afferents. I. Central relays for modulation of spinal nociceptive transmission.

1. Supraspinal relays for vagal afferent modulation of responses of spinal dorsal horn neurons to 50 degrees C heating of the skin were examined by the use of nonselective, reversible local anesthesia or soma-selective, irreversible neurotoxic damage of neural tissue. Eighty-five neurons were isolated in the lumbar spinal dorsal horn of 80 pentobarbital-anesthetized, paralyzed rats. All neurons studied had receptive fields on the glabrous skin of the plantar surface of the ipsilateral hind paw and responded to mechanical stimuli of both low and high intensity as well as noxious thermal stimulation. 2. Intensity-dependent modulation by vagal afferent stimulation (VAS) of neuronal responses to heating of the skin was established. Responses of 40 units were facilitated by low and inhibited by greater intensities of VAS. Another 36 units were only inhibited by VAS, and four were only facilitated. 3. Local anesthesia of the dorsolateral pons by bilateral microinjections of lidocaine (4%, 0.5 microliter) were made to examine the contribution of this area to VAS-produced spinal modulation. The microinjection of lidocaine bilaterally into the ventral locus coeruleus/subcoeruleus (LC/SC) reversibly and significantly attenuated VAS-produced inhibition of unit responses to heat from 63 to 89% of control and abolished VAS-produced facilitation. The microinjection of lidocaine bilaterally into the dorsal LC had no significant effect on VAS-produced modulation of spinal dorsal horn neurons. 4. Ibotenic acid (10 micrograms, 0.5 microliter) was microinjected into the dorsolateral pons to determine the relative contributions of cell bodies in this area to VAS-produced spinal modulation. Unilateral microinjection of ibotenic acid into the LC/SC ipsilateral to the vagus nerve stimulated had no significant effect on VAS-produced inhibition but significantly attenuated VAS-produced facilitation of unit responses to heat. Bilateral microinjections of ibotenic acid significantly attenuated VAS-produced inhibition of unit responses to heat from 48 to 94% of control. 5. Local anesthesia of the medial rostroventral medulla (RVM), primarily the nucleus raphe magnus (NRM), significantly attenuated VAS-produced inhibition of unit responses to heat from 55 to 87% of control but had no significant effect on VAS-produced facilitation. Microinjection of ibotenic acid into the RVM also significantly reduced VAS-produced inhibition of unit responses to heat. No significant change in VAS-produced spinal modulation was found after lidocaine microinjection into areas dorsal to the NRM, the nucleus raphe pallidus, or the olivary nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Electrical stimulation of cervical vagal afferents. II. Central relays for behavioral antinociception and arterial blood pressure decreases.

1. Supraspinal substrates mediating vagal afferent stimulation (VAS)-induced inhibition of the nociceptive tail-flick reflex were examined by the use of the soma-selective neurotoxin ibotenic acid and the nonselective local anesthetic lidocaine. Fifty rats were studied in the lightly anesthetized state maintained with pentobarbital sodium. 2. The threshold intensity of VAS required to inhibit the tail-flick reflex to a cut-off latency of 10 s was established in all rats. Ibotenic acid (5 or 10 micrograms, 0.5 microliter) or lidocaine (4%, 0.5 microliter) was then microinjected into various regions of the brain stem followed by reestablishment of the intensity of VAS required to produce inhibition of the tail-flick reflex. 3. Microinjections of ibotenic acid into the ipsilateral nucleus tractus solitarius (NTS), medial rostroventral medulla (principally the nucleus raphe magnus; NRM), or bilaterally into the dorsolateral pons (principally the locus coeruleus/subcoeruleus; LC/SC), significantly increased the threshold intensity of VAS required to inhibit the tail-flick reflex. Microinjections of ibotenic acid into either the rostral or caudal ventrolateral medulla (RVLM or CVLM, respectively) ipsilateral to the vagus nerve stimulated or ipsilateral LC/SC did not significantly affect the inhibition produced by VAS. Arterial blood pressure decreases produced by VAS were significantly attenuated or eliminated after microinjections of ibotenic acid into the NTS, RVLM, CVLM, or NRM. Lidocaine microinjected into the ipsilateral CVLM also significantly increased the intensity of VAS required to inhibit the tail-flick reflex. 4. These outcomes obtained with behavioral measures are consistent with the outcomes of the preceding study using electrophysiological measures in establishing that cells in the NTS, LC/SC, and NRM regions and fibers of passage in the CVLM are important in mediating the inhibitory effects of VAS. The present studies confirm previous reports of the importance of the RVLM and CVLM in VAS-produced depressor responses but also demonstrate that the NRM is critical for this cardiovascular response.

Animals↗

PubMed1989

Vagal afferent modulation of spinal nociceptive transmission in the rat.

1. The effects of vagal afferent stimulation (VAS) on spinal nociceptive transmission and the spinal pathway(s) mediating VAS-produced effects were examined in pentobarbital sodium- and urethane-anesthetized, paralyzed rats. The 60 units studied responded to mechanical stimuli and noxious heating (50 degrees C) of cutaneous receptive fields confined to the glabrous skin of the toes and footpads. Recording sites were located in laminae I-VI of the L3-L5 spinal segments. 2. VAS facilitated and inhibited neuronal responses to heat. In pentobarbital-anesthetized rats, responses of most (24/44) units were facilitated by low and inhibited by higher intensities of VAS. Responses of some units (15/44) were only inhibited and others (4/44) only facilitated by VAS. Inhibition produced by VAS was intensity-, pulse width-, frequency-, and stimulation duration-dependent. In urethane-anesthetized rats, responses of 6/16 units were initially facilitated, then inhibited as the intensity of VAS was increased; responses of nine units were inhibited by VAS. Quantitative comparisons of recruitment indices, mean thresholds for inhibition and mean intensities to inhibit unit responses to heat to 50% of control revealed no significant differences between the two anesthetic conditions. 3. The effects of VAS on neuronal responses to heat were dissociable from its effect on blood pressure. Regardless of the effect of VAS on unit responses to noxious heat, VAS consistently produced intensity-dependent depressor responses. The latencies to onset of inhibition and facilitation by VAS were determined by a cumulative sum technique and bin-by-bin analysis of peristimulus time histograms. The apparent latencies were 91 +/- 11 (SE) ms for inhibition and 278 +/- 59 ms for facilitation, both of which occurred before changes in blood pressure. Finally, microinjections of lidocaine into the ventrolateral funiculus (VLF) or transections of the dorsolateral funiculus (DLF) of the thoracic spinal cord attenuated VAS-produced effects on neuronal responses, but did not affect VAS-induced depressor responses. 4. The responses of 11 dorsal horn units to graded noxious heating of the skin were studied; the stimulus-response functions (SRF) were linear and monotonic throughout the temperature range examined (42-52 degrees C). VAS at intensities which inhibited unit responses to heat significantly decreased the slope of the SRF. VAS at intensities which facilitated unit responses to heat produced a leftward, parallel shift of the SRF.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1988

Vagal afferent modulation of a nociceptive reflex in rats: involvement of spinal opioid and monoamine receptors.

Modulation of the spinal nociceptive tail flick (TF) reflex by electrical stimulation of subdiaphragmatic or cervical vagal afferent fibers was characterized in rats lightly anesthetized with pentobarbital. Cervical vagal afferent stimulation (VAS) inhibited the TF reflex in a pulse width-, frequency-, and intensity-dependent fashion. The optimum parameters for inhibition of the TF reflex were determined to be 2.0 ms pulse width, 20 Hz frequency with a threshold (T) current of 60 microA. Cervical VAS at 0.2-0.6 T facilitated the TF reflex. Cervical VAS at T typically produced a depressor arterial blood pressure response, but inhibition of the TF reflex by VAS was not due to changes in blood pressure. Subdiaphragmatic VAS also inhibited the TF reflex and generally produced a pressor effect, but did not facilitate the TF reflex at intensities of stimulation less than T as did cervical VAS. The parameters of cervical VAS required for inhibition of TF reflex suggest that excitation of high-threshold, unmyelinated fibers are important in VAS-induced descending inhibition. The intrathecal administration of pharmacologic receptor antagonists into the subarachnoid space of the lumbar enlargement indicated that the opioid receptor antagonist naloxone produced a dose-dependent antagonism of cervical VAS-produced inhibition of TF reflex, but single doses of either phentolamine or methysergide (30 micrograms each) failed to affect the inhibition by VAS. Combined intrathecal injection of both phentolamine and methysergide (30 micrograms each), however, significantly attenuated inhibition of the TF reflex by cervical VAS. These results suggest that cervical VAS engages a spinal opioid system and co-activates descending serotonergic and noradrenergic systems to modulate spinal nociceptive processing.

Afferent Pathways↗

PubMed1988

Medullary substrates mediating antinociception produced by electrical stimulation of the vagus.

Electrical stimulation of afferents of the right cervical vagus inhibited the tail-flick reflex elicited by noxious heat in barbiturate-anesthetized rats. This inhibitory effect was eliminated in rats receiving local anesthetic blockade of either the nucleus tractus solitarii (NTS), the lateral reticular nuclei, the nucleus raphe magnus-medullary reticular formation, or nucleus raphe obscurus regions of the medulla. Similarly, the vasodepressor and bradycardic effects of vagal stimulation were either attenuated or eliminated by local anesthetic blockade of these regions. Microinjection of the non-specific glutamate antagonist gamma-D-glutamylglycine (DGG) into the NTS region also eliminated vagally evoked inhibition of the tail-flick reflex, hypotension, and bradycardia. Conversely, microinjection of glutamate into the NTS region resulted in inhibition of the tail-flick reflex, hypotension, and bradycardia. These findings with DGG and glutamate are consistent with the view that glutamate serves as a neurotransmitter of the primary vagal afferents mediating these antinociceptive and cardiovascular responses. These results are discussed in terms of vagal afferent influences on somatosensory, somatomotor, and cardiovascular function.

Afferent Pathways↗

PubMed1988

Effects of intrathecal antagonists on the antinociception, hypotension, and bradycardia produced by intravenous administration of [D-Ala2]-methionine enkephalinamide (DALA) in the rat.

DALA is a synthetic pentapeptide that produces inhibition of the tail-flick reflex evoked by radiant heat, as well as hypotension and bradycardia. Two experiments examined the effects of administration of various receptor antagonists into the subarachnoid space of the lumbar spinal cord on the antinociception produced by IV administration of DALA. Experiment 1 showed that intrathecal administration of 30 micrograms of phentolamine produced a significant reduction in the antinociceptive effect of DALA, while naloxone (30 micrograms), methysergide (30 micrograms), or vehicle control had no effect. Experiment 2 showed that intrathecal administration of combinations of either phentolamine and methysergide, or phentolamine and naloxone, were no more effective in reducing the antinociceptive effect of DALA than administration of phentolamine alone. These data demonstrate the involvement of descending noradrenergic systems in the production of antinociception by IV DALA. Further, they indicate that the antinociception produced by DALA is independent of a direct spinal action of the drug.

Analgesics↗

PubMed1988

Characterization of antinociception produced by glutamate microinjection in the nucleus tractus solitarius and the nucleus reticularis ventralis.

Four experiments examined the role of the nucleus tractus solitarius (NTS) and subjacent nucleus reticularis ventralis (NRV) in the production of antinociception. Experiment 1 showed that microinjection of glutamate (50 nmol) into the caudal NTS resulted in inhibition of the tail-flick reflex, hypotension, and mild bradycardia, whereas microinjection of glutamate into the rostral NTS resulted only in hypotension and mild bradycardia. Microinjections of glutamate into the NRV resulted in inhibition of the tail-flick reflex, hypertension, and mild bradycardia. Experiment 2 demonstrated that the magnitude of the antinociceptive and cardiovascular responses resulting from glutamate microinjections into both the depressor and pressor regions were dose dependent. Experiment 3 showed that the antinociceptive effects resulting from microinjections of glutamate into either the depressor or pressor regions could not be antagonized by phentolamine (30 micrograms), methysergide (30 micrograms), or naloxone (30 micrograms) alone, but the combined intrathecal administration of phentolamine and methysergide (7.5, 15, or 30 micrograms of each) attenuated the antinociception resulting from microinjection of glutamate into either depressor or pressor regions in a dose-dependent fashion. Experiment 4 showed that systemic administration of hexamethonium blocked the pressor response produced by microinjection of glutamate into the NRV but did not reduce the antinociceptive effect of the microinjection. These findings are consistent with a role for the NTS and NRV in the production of antinociception.

Animals↗

PubMed1987

Medullary substrates of descending spinal inhibition activated by intravenous administration of [D-Ala2]methionine enkephalinamide in the rat.

Two experiments were performed in pentobarbital-anesthetized rats to provide information about the locus of the descending inhibitory system(s) in the brainstem engaged by [D-Ala2]methionine enkephalinamide (DALA) activation of vagal afferents. In Expt. 1, local anesthetic block of either the medial medullary nucleus raphe magnus (NRM) or the combined NRM-lateral medullary reticular formation (MRF) region failed to affect DALA-induced inhibition of the tail-flick reflex or reflex bradycardia. The hypotensive action of DALA was marginally enhanced in rats with a combined NRM-MRF local anesthetic block. However, inhibition of the tail-flick reflex produced by electrical stimulation in the NRM-MRF was eliminated by the local anesthetic. In Expt. 2, local anesthetic blocks of regions at the level of and caudal to obex were effective in blocking DALA-induced inhibition of the tail-flick reflex. These regions included lateral sites approximately 0.4 mm rostral to obex to -2.4 mm caudal to obex, and midline sites approximately -2.4 to -3.2 mm caudal to obex. These findings suggest that brainstem areas mediating DALA-induced antinociception are lateral to the midline at the level of the obex. The spinopetal efferents mediating antinociception then course medially and ventrally, and finally course bilaterally in the dorsolateral funiculi before terminating in the spinal dorsal horn.

Anesthetics, Local↗

PubMed1986

Volume loading hypoalgesia in SHR, WKY and F1 offspring of a SHR x WKY cross.

The effects of volume loading on a nociceptive reflex, arterial blood pressure and heart rate were studied in spontaneously hypertensive rats (SHRs), Wistar Kyoto normotensive rats (WKYs) and the F1 offspring of a SHR x WKY cross. Volume loading resulted in significantly greater inhibition of the tail-flick reflex to painful radiant heat in SHRs compared to WKYs. The F1 offspring of a SHR x WKY cross showed levels of hypoalgesia to volume loading that were intermediate to those of SHRs and WKYs. There were no differences between these strains in their hypotensive and bradycardic responses to volume loading. These findings are discussed in terms of cardiovascular-somatosensory interactions.

Animals↗

PubMed1986

[D-Ala2]-methionine enkephalinamide (DALA): characterization of antinociceptive, cardiovascular, and autonomic nervous system actions in conscious and pentobarbital-anesthetized rats.

The antinociceptive, cardiovascular, and autonomic nervous system actions of [D-Ala2]-methionine enkephalinamide (DALA) were assessed in conscious and pentobarbital-anesthetized rats. Intravenous administration of DALA inhibited the tail-flick reflex evoked by noxious radiant heat in both conscious and pentobarbital-anesthetized rats. In general, the magnitude of the inhibition was not significantly affected by the presence of pentobarbital-anesthesia. DALA also induced hypotension and bradycardia in these rats, but these responses were significantly attenuated by pentobarbital-anesthesia. Arterial blood flows were initially decreased and vascular resistances increased in mesenteric, renal, and hindquarter beds following DALA administration, but these parameters rapidly returned to baseline levels except in the hindquarter bed where flows increased significantly above baseline levels. All of the changes in blood flows were significantly greater in conscious compared to pentobarbital-anesthetized rats. In intact pentobarbital-anesthetized rats, DALA induced inhibition of renal sympathetic nerve activity. However, DALA induced a pressor response with a brief increase in renal sympathetic nerve activity in rats with bilateral vagotomy. Similarly, in the conscious rat with ganglionic blockade, DALA induces a brief pressor response. These outcomes indicate that the brief hypotension observed in the intact rat following administration of DALA is probably the net outcome of a large vagally-induced decrease in sympathetic tone and a small increase in sympathetic tone of either neurogenic or peripheral origin. These outcomes are discussed in terms of cardiovascular-somatosensory interactions.

Anesthesia↗