Central neurotransmitter systems in the morphine suppression of jaw-opening reflex in rabbits: the cholinergic system.

The possible participation of the central cholinergic system in morphine suppression of the jaw-opening reflex was investigated in rabbits lightly anesthetized with pentobarbital sodium (30 mg/kg, i.v.). The averaged amplitude of EMG signals from the digastric muscle, evoked by intrapulpal stimulation, was used as the pain index. Drugs were administered directly into the cerebral circulation via a carotid artery, cannulated centrifugally from the heart. Injection of a subliminal dose of morphine (3 mg/kg) produced no appreciable effect on the jaw-opening reflex, which was, however, significantly depressed after a subsequent injection of physostigmine (0.1 mg/kg). Such physostigmine-potentiated analgesia still persisted after atropine administration (1 or 5 mg/kg). An optimal dose of morphine (6 mg/kg) was found to elicit drastic inhibition of the evoked digastric activity, which was again not reversed by atropine (1 or 5 mg/kg). We concluded that the cholinergic system is involved in the morphine suppression of the jaw-opening reflex, and suggest that shifting of the balance between central neurotransmitter systems may be a key to the precipitation of the analgesic process induced by the opiate.     

Responses of caudal brain stem neurons to vaginal and somatosensory stimulation in the rat and evidence of genital-nociceptive interactions.

In rabbits lightly anesthetized with pentobarbital, the effects of injecting morphine and its antagonist, nalorphine, directly into the cerebral circulation via a carotid artery cannulation, on the jaw-opening reflex elicited by intradental stimulation, were studied. Using averaged electromyogram signals from the digastric muscle as the index, a single dose of morphine (3 mg/kg) was found to produce only a transient depression of the jaw-opening reflex. After a second, cumulative injection of morphine (3 mg/kg), the jaw-opening reflex was sufficiently inhibited for at least 30 min. The morphine-induced analgesia could be reversed by nalorphine, indicating that such action was truly pharmacological. The likelihood of morphine acting on some central sites and promoting the release of neurotransmitters which produce inhibition of transmission of nociceptive information from the dental pulp is discussed in the light of recent physiological and pharmacological linkage between morphine-triggered and central stimulation-induced analgesia.     

Differential effects of clonidine on pain, arterial blood pressure, and heart rate in the cat: lack of interactions with naloxone

In cats anesthetized with alpha-chloralose and urethane, intravertebral administration of clonidine (4 and 10 micrograms/kg) dose-dependently suppressed the jaw-opening reflex, arterial blood pressure, and heart rate. For a given dose, there was a differential degree of inhibition in the order of analgesia much greater than hypotension greater than bradycardia. Naloxone injections (0.4 and 1.0 mg/kg, i.vert.) essentially failed to antagonize these effects, suggesting the lack of involvement of the opiate receptors or endogenous opioids in these processes. Furthermore, pain suppression by clonidine appeared to be independent of the vasodepression and cardioinhibition it promoted. It is possible that neural mechanisms responsible for clonidine-induced antinociception, hypotension, and bradycardia are likely to have differential sensitivities to the imidazoline compound, regardless of whether they exist in separate central sites or in subpopulations of neurons within common neural substrates.     

Central neurotransmitter systems in the morphine suppression of jaw-opening reflex in rabbits: The dopaminergic system

The possible participation of the central dopaminergic system in the suppression by morphine of the jaw-opening reflex was investigated in rabbits lightly anesthetized with pentobarbital sodium (30 mg/kg, i.v.). The averaged amplitude of EMG signals from the digastric muscle, evoked by intrapulpal stimulation, was used as the pain index. Drugs were administered either directly into the cerebral circulation via a cannulated carotid artery or intraperitoneally. Pretreatment of the animals with haloperidol (0.5 mg/kg) or pimozide (0.5 mg/kg) essentially eliminated the inhibitory action of an optimal dose of morphine (6 mg/kg) on the jaw-opening reflex. Such antagonistic action of pimozide (and to a lesser extent, of haloperidol) on the opiate effect could be reversed by physostigmine (0.1 mg/kg). Apomorphine (0.5 mg/kg) pretreatment sufficiently potentiated the effect of a suboptimal dose of morphine (3 mg/kg), resulting in significant suppression of the evoked digastric activities. We concluded that the dopaminergic system is involved synergistically in morphine suppression of the jaw-opening reflex; the present study also reinforced a previous proposal that shifting of the balance between central neurotransmitter systems may be a key to the precipitation of the analgesic process induced by the opiate.     

Involvement of the noradrenergic system in modulating the blink reflex in humans

Several researches have shown that the spinal reflex transmission in animals, as well as humans, was inhibited by alpha(2)-agonists, due to a disfacilitation of tonic noradrenergic control on motoneuronal output. To understand better the mechanisms regulating certain aspects of motor activity, here we reinvestigated the possible role of noradrenergic systems in modulating reflex activity of the brainstem in humans. To this aim, blink reflex responses (R1 and R2) evoked by electrical stimulation of the supraorbital nerve were electromyographically recorded in healthy volunteers. Both R1 and R2 areas were measured at 10-min intervals before and after i.v. injection of alpha(2)-agonist clonidine (0.5 microg/kg). The substance induced consistent depression of R1, which reached its maximum 40 min after drug administration (-43% of the control values). Ipsilateral R2 area resulted little affected by clonidine (-15% at 50 min), whereas no effects were observed in contralateral R2. Blood pressure values were never altered by drug injections. These results, taken together with previous observations, support the hypothesis that alpha(2)-agonist substances may cause a transient inactivation of noradrenergic neurons, thus releasing neurons involved in the circuitry of the blink reflex from a facilitatory drive. Since clonidine differentially modulated blink reflex responses, it is likely to assume that such a disfacilitation concerns mostly pontine units mediating the R1. However, the complexity of clonidine's effects at multiple pre- and postsynaptic sites does not allow us to exclude that other systems are involved in the alpha(2)-mediated control of facial motoneurons.     

Iontophoretic analysis of the pharmacologic mechanisms responsible for initiation and modulation of trigeminal motoneuronal discharge evoked by intra-oral afferent stimulation

This study investigated the effects of iontophoretic application of excitatory amino acid (EAA) and norepinephrine (NE) agonists and antagonists on synaptic transmission to individual jaw-opener motoneurons (digastric) during activation of the jaw-opening reflex (JOR) evoked by stimulation of either fibers within the oral mucosa (OM), or tooth-pulp (TP). During both OM and TP stimulation, kynurenic acid (KYN), a wide-spectrum EAA antagonist, suppressed jaw-opener motoneuron discharge. Application of APV, an NMDA receptor antagonist, also suppressed motoneuron discharge evoked by TP stimulation, but produced minimal effects on motoneuron discharge evoked by OM stimulation. These data suggest a role of EAA in mediating synaptic transmission from last-order interneurons to jaw-opener motoneurons during the jaw-opening reflex evoked by intra-oral stimulation. Iontophoretic application of NE produced dual effects (facilitation or suppression) on motoneuronal discharge evoked by OM or TP stimulation. The effects were not related to the mode of motoneuronal activation. Iontophoretic application of the alpha 1 agonist, phenylephrine, facilitated motoneuronal discharge. In contrast, application of the alpha 2 agonist, clonidine, suppressed motoneuronal discharge during intra-oral stimulation. These effects were antagonized by prior iontophoretic application of the alpha 1 antagonist, prazosin, or the alpha 2 antagonist, yohimbine, respectively. In those cells in which the predominant effect of NE application on synaptic transmission was either facilitation or suppression of motoneuronal discharge, prior iontophoretic application of prazosin or yohimbine, respectively, antagonized the effects of NE application. These data suggest that NE can modulate synaptic transmission to jaw-opener motoneurons evoked by intra-oral stimulation via activation of alpha 1 or alpha 2 adrenoreceptors on trigeminal motoneurons.     

Tooth pulp-evoked jaw-opening reflex in the cat: evidence for central facilitation induced by noxious discharge in the intradental nerve fibers

The tooth pulp-evoked jaw-opening reflex was studied in the barbiturate-anesthetized cat. At liminal intensity of the stimulus, a stable short-latency response was obtained in the digastricus and in the tongue. At a higher stimulus intensity, there occasionally appeared to be a prolonged discharge of variable duration in the digastricus, and a second period of activity in the tongue after a silent period. The threshold intensity for these late discharges was supraliminal for the intradental A-fibers and subliminal for intradental C-fibers. Noxious conditioning stimulation of a tooth led to a temporary decrease of the threshold for the jaw-opening reflex elicited from a contralateral or adjacent tooth; only conditioning stimulation at an intensity producing a marked arousal reaction was effective in this respect. Infiltration of the tooth apex with epinephrine produced a local elevation of the threshold for the tooth pulp-evoked jaw-opening reflex. Distant noxious conditioning stimulation (tail pinch) did not influence the jaw-opening threshold. The results indicated that based on some central mechanisms, conditioning noxious stimulation of a tooth can produce a facilitation of the jaw-opening reflex.     

Site and action of electroacupuncture-induced effects on the rat jaw-opening reflex

The aims of the present study were to identify the specificity of the pain-relieving effects of electroacupuncture (EA) stimulation by comparing its effects on the jaw-opening reflex evoked by noxious and nonnoxious inputs, and to identify the site of action of EA in the jaw-opening reflex arc. I examined the EA effects on three responses involved in the jaw-opening reflex arc using Wistar albino rats: (i) the jaw-opening reflex to stimulation of the orofacial region, (ii) evoked responses in a secondary neuron site, and (iii) jaw-opening responses to stimulation of the secondary neuron site. EA stimulation almost suppressed the responses involved in the pathway of the jaw-opening reflex evoked by high-threshold afferent fibers, whereas it scarcely affected those in the pathway of the reflex evoked by low-threshold afferent fibers. From a comparison of the degree of suppression of the three responses, I suggest that EA suppression of the jaw-opening reflex was induced chiefly on the activity of the spinal trigeminal nucleus. In conclusion, it can be said that EA stimulation is almost selectively effective on the activity of the secondary neuron site involved in the jaw-opening reflex evoked by noxious input.     

Alpha 2-adrenoreceptor subtypes regulate ACTH and beta-endorphin secretions during stress in the rat

The effect of different alpha 2-adrenoreceptor subtype agonists and antagonists on adrenocorticotrop hormone (ACTH) and beta-endorphin release induced by ether stress was examined. Ether inhalation-induced ACTH and beta-endorphin increase was inhibited by i.c.v. administration of 30 micrograms but not 1 and 10 micrograms clonidine (alpha 2-adrenoreceptor agonist). I.c.v. oxymetazoline (alpha 2A-adrenoreceptor agonist; 1-10-30 micrograms) or the alpha 1-agonist methoxamine (100 micrograms/rat) failed to inhibit the stress-induced rise. Pretreatment with the alpha 1/alpha 2B.C-antagonist prazosin (0.5 mg/kg, i.p.) prevented the effect of clonidine on the ether stress, while the alpha 1/alpha 2A-antagonist WB-4101 (0.5 mg/kg, i.p.) was unable to counteract the inhibitory effect of clonidine. Prazosin alone had no effect on the ether-induced plasma ACTH and beta-endorphin elevation. These results suggest that noradrenaline in the central nervous system may inhibit the stress-induced hypothalamo-pituitary-axis and pituitary beta-endorphin activation via alpha 2B.C-adrenoceptor subtypes and prazosin may antagonize its effect on these receptors.     

Potent antinociceptive effects of clonidine systemically administered in an experimental model of clinical pain, the arthritic rat.

The effects of various doses of the alpha-2 adrenoceptor agonist clonidine administered systemically (30, 50 and 100 micrograms/kg i.v.), were investigated on the vocalization threshold to paw pressure in normal rats and in rats with Freund's adjuvant-induced arthritis. Previous results have suggested that there is an increase in the activity of the bulbospinal noradrenergic systems in these arthritic animals. In the present study, clonidine led to significant antinociceptive effects in both groups of rats. Clonidine was found to be highly effective in arthritic animals, even at the lower concentration: the elevation in threshold produced by 30 micrograms/kg i.v. was 160% in arthritic vs. 124% in normal rats. The effects of clonidine were prevented dose-dependently by pretreatment with yohimbine or idazoxan 250 to 1000 micrograms/kg i.v., in the two groups of rats, indicating clearly that the dose-dependent effects of i.v. clonidine are mediated by alpha-2 adrenoceptors.     

Yohimbine reverses the exhaustion of the coital reflex in spinal male rats

The possible participation of the central noradrenergic system in the expression of the ejaculatory reflex of the rat was explored by evaluating the effects of the alpha(2)-adrenoceptor antagonist, yohimbine, on the exhausted coital reflex model. Male sexually experienced Wistar rats, subjected to the coital reflex exhaustion paradigm received a single i.v. injection of yohimbine (10 microg/animal), immediately after reaching exhaustion. Enhancement of noradrenergic transmission by yohimbine provoked the immediate expression of a single ejaculatory genital motor pattern (GMP) similar to a first reflexively evoked one, but in the absence of urethral mechanical stimulation. Pre-treatment with clonidine (10 microg/animal) completely prevented the yohimbine-induced GMP, implying that its effect was exerted upon alpha(2)-adrenoceptors. Clonidine treatment per se induced the expression of a single GMP, similar to a last reflexively evoked one, that was completely blocked by pre-treatment with prazosin (1 microg/animal) indicating that it was due to the alpha(1) properties of clonidine. Administration of prazosin previous to yohimbine did not interfere with the expression of the GMP but attenuated it, suggesting the involvement of alpha(1)-adrenoceptors in the yohimbine-induced motor response. Data reveal a facilitatory influence of the noradrenergic system on ejaculatory function mediated by both alpha(1)- and alpha(2)-adrenoceptors and support the notion of yohimbine acting at a spinal level.     

Comparison of drugs with different selectivity for central alpha 1-and alpha 2-adrenoceptors in animal models of epilepsy

The effects of two drugs which differ in selectivity for central alpha 1- and alpha 2-adrenoceptors were compared in different animal models of epilepsy. Clonidine, a selective alpha2-adrenoceptor agonist, up to 0.5 mg/kg i.p. was inactive against electroconvulsions in mice, but decreased the threshold for electroconvulsions in rats, whereas it exerted anticonvulsant effects against seizures induced by pentylenetetrazol in mice, amygdala kindling in rats and air blast stimulation in seizure-sensitive gerbils. In gerbils, the anticonvulsant effect of clonidine was counteracted by pretreatment with the alpha2-antagonist yohimbine (2.5 mg/kg i.p.), but not by the alpha 1-selective antagonist corynanthine (10 mg/kg i.p.). St 587 [2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine], a highly alpha 1-selective agonist which easily penetrates into the brain, up to 20 mg/kg i.p. exerted no effects on the thresholds for electroshock and pentylenetetrazol-induced seizures in mice and rats, but displayed significant anticonvulsant efficacy in kindled rats and epileptic gerbils. In gerbils, corynanthine but not yohimbine antagonized the anticonvulsant effect of St 587. The data indicate that, at least in certain seizure models, anticonvulsant effects can be reached via stimulation of both alpha 1- and alpha 2-adrenoceptors.     

Activation of central mu-opioid receptors is involved in clonidine analgesia in rats

The analgesic effect of clonidine in spontaneously hypertensive rats (SHR) and in normotensive Sprague-Dawley (SD) rats was assessed by using the formalin pain test. The analgesic response of SD rats to low doses (15-60 micrograms/kg i.p.) but not to a high dose (150 micrograms/kg i.p.) of clonidine was inhibited by naloxone, 2 mg/kg i.p., and similar interaction was noted in SHR. In both rat strains, the analgesic response to low i.p. doses of clonidine was also inhibited by injection of 5 micrograms of naloxone or 7 micrograms of beta-funaltrexamine, a mu-receptor antagonist, into the lateral cerebral ventricle. I.c.v. injection of 5 micrograms of ICI 174864, a delta-receptor antagonist, potentiated or did not influence clonidine analgesia in SD rats and SHR, respectively. It is concluded that the analgesic response to clonidine involves activation of central mu-opioid receptors in both SHR and SD rats, possibly by an endogenous opioid released by clonidine.     

Tonic descending inhibition of the spinal cardio-sympathetic reflex in the cat

Electrical stimulation of the left inferior cardiac nerve elicited a two-component reflex potential (spinal and supraspinal reflexes) in the ipsilateral white ramus T3 from which recordings were made in chloralose-anaesthetised cats. Reversible interruption of all spinal pathways achieved by cooling the spinal cord at C2/C3 produced an enhancement of the spinal reflex and abolished the supraspinal reflex, the latter usually being the more prominent reflex potential prior to spinal cord block. The spinal cord block-induced increase in the amplitude of the spinal reflex was, however, less than the increase observed during stimulation of the somatic intercostal nerve T4. Recordings of the afferent volley following cardiac nerve stimulation and analysis of the stimulus-reflex response relationship in neuraxis-blocked cats indicated that the spinal reflex as determined here was activated by A delta afferent fibres. However, if stimulus strength was raised above C-fibre threshold, spinal cord block revealed in addition a late spinal reflex response. In some cases, the appearance of this late potential was accompanied by a secondary decline of the earlier spinal reflex potential, possibly indicating C-fibre-mediated afferent inhibition. Neither baroreceptor activation nor denervation had any effect on spinal reflex amplitudes. Pharmacologically, clonidine given i.v. to cats with a blocked neuraxis reduced the spinal reflex amplitudes to pre-block values, an action which could be antagonised by the subsequent administration of the alpha 2-adrenoceptor antagonist rauwolscine. When given to non-pretreated cats with intact neuraxis, however, neither rauwolscine nor its analog yohimbine were capable of inducing a persistent release from tonic inhibition. The results suggest that both purely visceral and somato-visceral reflexes are subject to tonic descending inhibition, but they do not support the hypothesis that a catecholamine is the responsible transmitter mediating this inhibition.     

Modulatory action of noradrenergic system on spinal motoneurons in humans.

Previous findings in animals demonstrated that the noradrenergic coeruleospinal system exerts a tonic facilitation on spinal reflexes and that activation of alpha2-autoinhibitory receptors can be responsible for a disfacilitation of the spinal activity. To investigate this issue further, we examined whether this system is also involved in descending facilitatory control of spinal motoneurons in healthy humans. The H-reflex technique was utilized to assay the motoneuronal excitability. The ratio between the maximal reflex response (H) and maximal direct response (M) was determined in each subject and was calculated at 10 min intervals before and after i.v. administration of the alpha2-agonist clonidine (0.5 microg/kg). In all subjects a marked decrease of the H/M ratio, due to depression of the H response, occurred 10 min following the clonidine injection and reached its maximum within 30 min. No significant changes of blood pressure values were provoked by drug injections. These results suggest that an autoinhibitory action may be induced by alpha2-receptor activation of locus coeruleus neurons in humans, and that this device may serve as a mechanism for a myotonolytic action on spinal motoneurons.     

Investigation of the role of alpha‐2 adrenergic receptors on prepulse inhibition of acoustic startle reflex in rats

Objectives : Alpha‐2 adrenergic receptors target several behavioral functions. These receptors may connect with the brain pathways mediating sensorimotor gating system that associate with psychoses, and the literature that investigate the relationship between alpha‐2 receptors and sensorimotor gating system is very limited and some results are controversial. Thus, we aimed to investigate the role of alpha‐2 receptors on prepulse inhibition (PPI) of acoustic startle reflex which is a measure of sensorimotor gating. Experimental Design : Adult male Wistar rats were subjects. PPI was measured as the per cent inhibition of the startle reflex produced by a startling pulse stimulus. The average PPI levels were used in the further analyses. Clonidine (0.03–1 mg/kg), an agonist of alpha‐2 receptors, idazoxan (10 mg/kg), an antagonist alpha‐2 receptors, and saline were injected to rats intraperitoneally. PPI was evaluated at two different startle intensity levels (78 and 86 dB, respectively). Principal Observations : Treatments produced some significant changes on PPI of startle reflex at all two levels of startle intensity. While clonidine (0.06, 0.25, 0.5, and 1 mg/kg) disrupted significantly PPI, idazoxan (10 mg/kg) did not produce any significant effect on PPI. However, pretreatment with idazoxan reversed significantly clonidine‐induced disruption of PPI. Neither idazoxan (10 mg/kg) nor clonidine (1 mg/kg) produces any significant change on locomotor activity in naive rats. Conclusion : Because idazoxan and clonidine also act through imidazoline receptors, our results suggest that alpha‐2 and/or imidazoline receptors are associated with PPI of acoustic startle reflex in rats. Stimulation of these receptors may cause sensorimotor gating disturbances.     

Chronic variable stress induces supersensitivity of central α2-adrenoceptors which modulate the jaw-opening reflex in the rat

In a previous study, we found that the sensitivity of central postsynaptic α₂-adrenoceptors which modulate, in an inhibitory way, the activity of the jaw-opening reflex (JOR) is reduced after chronic repeated stress (tail pinch) in the rat. The aim of this study was to assess the effects of exposure to a chronic variable stress regime on these adrenoceptors. To do this, the digastric electromyographic responses elicited by orofacial electrical stimulation after the intravenous administration of cumulative doses (×3.3) of the α₂-adrenoceptor agonist, clonidine (0.1–10 000 μg/kg), were recorded. As expected, in unmanipulated control rats, clonidine inhibited the reflex, in a dose-dependent manner, until abolition (ED₅₀=17.3±2.2 μg/kg). Single tail pinch did not significantly alter the ability of clonidine to abolish the reflex. However, chronic variable stress led to an enhancement of the inhibitory effect of clonidine on the amplitude of JOR, resulting in a shift to the left of the dose-response curve in comparison with that of the control group (ED₅₀ was reduced by 37%, P=0.032), without affecting either the estimated maximum effect for the agonist or the slope of the inhibitory function. This in vivo result indicates that chronic variable stress leads to an increased sensitivity of central α₂-adrenoceptors which modulate JOR, in contrast to the desensitization of these adrenoceptors found after repeated exposure to the same stressor.     

Suppression of the jaw-opening reflex by conditioning A-delta fiber stimulation and electroacupuncture in the rat

Selective conditioning stimulation of A-delta fibers in the peripheral nerve with triangular pulses as well as electroacupuncture to the hind leg (5 Hz, 15 min) strongly suppressed the jaw-opening reflex in a lightly anesthetized rat, whereas maximal A-beta fiber stimulation with rectangular pulses was almost ineffective. Hence, the participation of A-delta fibers in electroacupuncture analgesia is suggested.     

Spinalization unmasks clonidine's alpha 1-adrenergic mediated excitation of the flexor reflex in rats

Clonidine exerts alpha 2-adrenergic mediated depressant effects on most behaviors measured in a normal animal. However, in the spinal-transected (spinalized) animal, clonidine apparently facilitates the flexor reflex through a stimulation of spinal alpha 1-adrenoceptors. The purpose of the present study was to determine if spinalization per se causes the shift in clonidine's profile from an alpha 2- to an alpha 1-adrenergic agonist. The hindlimb flexor reflex was elicited by electrical pulses delivered through electrodes implanted subcutaneously in the hindpaw and was measured with a force transducer and polygraph. In contrast to an alpha 2-adrenergic mediated inhibition of the flexor reflex in intact rats, clonidine produced an alpha 1-adrenergic mediated increase in flexor reflex amplitude in spinalized rats. Because decerebration did not alter the depression due to clonidine, and intraventricular (but not intrathecal) administration of oxymetazoline mimicked the effect of clonidine, the depressant effects of alpha 2-adrenergic agonists are mediated through alpha 2-adrenergic receptors localized in the brainstem. Alternate methods for inducing a functional spinal transection (spinal block with intrathecal procaine; spinal ligation) indicated that the shift in clonidine's effect from inhibition of the flexor reflex to excitation occurred immediately following spinalization. Spinal ligation did not produce alpha 1-adrenergic supersensitivity at 15 min or 2 hr after transection, as measured by alterations in [3H]prazosin receptor binding or behavioral responses to clonidine. Thus, the shift in clonidine's effects from alpha 2-adrenergic mediated inhibition of the flexor reflex in intact rats to alpha 1-adrenergic mediated excitation in spinalized rats results because spinal transection unmasks clonidine's alpha 1-adrenergic stimulatory effect. Other conditions under which clonidine exerts alpha 1-adrenoceptor mediated excitatory effects on behavior are discussed.     

Inhibition of gastric motility by noxious chemical stimulation of interspinous tissues in the rat

In urethane anesthetized, adult male Wistar rats, noxious chemical stimulation of the mid to lower thoracic interspinous tissues, in the form of capsaicin injection, was accompanied by a pronounced increase in gastric sympathetic nerve activity and inhibition of gastric motility. Much weaker effects on gastric sympathetic nerve activity and gastric motility were observed with similar stimulation of the lower lumbar interspinous tissues. The inhibitory response of gastric motility to thoracic stimulation was preserved in spinalized animals, somewhat diminished in vagotomized animals and was abolished in most animals from which the coeliac ganglion had been extirpated. In vagotomized animals, treatment with 1 mg/kg propranolol i.v. did not cause any further attenuation of the inhibitory reflex. However, the inhibitory reflex was extinguished in vagotomized animals which received 1 mg/kg propranolol plus 10 mg/kg phentolamine i.v. These results suggest that noxious chemical stimulation of the interspinous tissues elicits a segmentally organized reflex which is mediated principally at the spinal level and which expresses itself principally, but not exclusively via sympathetic efferents traversing the coeliac ganglion. The expression of the reflex response appears to be largely dependent upon the integrity of alpha adrenergic receptors.