Noxious Somatic Stimulation Research Articles

NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation

NMDA receptors (NMDAR) are important in the development and maintenance of central sensitization. Our objective was to investigate the role of spinal neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were injected with acidic saline adjusted to pH 4.0 in the gastrocnemius muscle every other day for 12 days. In adult rats, NR1 and NR2B subunits were examined in the lumbo-sacral (LS) spinal cord. A baseline, visceromotor response (VMR) to graded colorectal distension (CRD) was recorded before and after administration of the NMDA antagonist, CGS-19755. Extracellular recordings were performed from CRD-sensitive LS spinal neurons and pelvic nerve afferents (PNA) before and after CGS-19755. Rats that received pH 4.0 saline injections demonstrated a significant increase in the expression NR2B subunits and VMR response to CRD>20mmHg. CGS-19755 (i.v. or i.t.) had no effect in naïve rats, but significantly decreased the response to CRD in pH 4.0 saline injected rats. CGS-19755 had no effect on the spontaneous firing of SL-A, but decreased that of SL-S. Similarly, CGS-19755 attenuates the responses of SL-S neurons to CRD, but had no effect on SL-A neurons or on the response characteristics of PNA fibers. Neonatal noxious somatic stimulation results in chronic visceral hyperalgesia and sensitizes a specific subpopulation of CRD-sensitive spinal neurons. The sensitization of these SL-S spinal neurons is attenuated by the NMDAR antagonist. The results of this study suggest that spinal NMDARs play an important role in the development of hyperalgesia early in life.

Comparison of Burst and Tonic Spinal Cord Stimulation on Spinal Neural Processing in an Animal Model

Spinal cord stimulation (SCS) using bursts of pulses suppressed neuropathic pain as well or better than tonic stimulation and limited the incidences of parasthesias. The present translational study explored possible differences in mechanisms of burst and tonic SCS on nociceptive spinal networks and/or the gracile nucleus supraspinal relay. Visceromotor reflexes (VMRs, a nociceptive response) or extracellular activity of either L6-S2 spinal neurons or gracile nucleus neurons were recorded during noxious somatic stimulation (pinching) and visceral stimulation (colorectal distension [CRD]) in anesthetized rats. A stimulating (unipolar, ball) electrode at L2-L3 delivered 40 Hz burst or tonic SCS at different intensities relative to motor threshold (MT). Average MTs for burst SCS were significantly lower than for tonic SCS. Burst SCS reduced the VMR more than tonic SCS. After high-intensity SCS (90% MT), spinal neuronal responses to CRD and pinch were reduced similarly for burst and tonic SCS. At low-intensity SCS (60% MT), only burst SCS significantly decreased the nociceptive somatic response. Tonic but not burst SCS significantly increased spontaneous activity of neurons in the gracile nucleus. Based on the clinically relevant burst versus tonic parameters used in this study, burst SCS is more efficacious than tonic SCS in attenuating visceral nociception. Burst and tonic SCS also suppress lumbosacral neuronal responses to noxious somatic and visceral stimuli; however, burst SCS has a greater inhibitory effect on the neuronal response to noxious somatic stimuli than to noxious visceral stimuli. Reduced or abolished paresthesia in patients may be due in part to burst SCS not increasing spontaneous activity of neurons in the gracile nucleus.

Noxious somatic stimuli diminish respiratory–sympathetic coupling by selective resetting of the respiratory rhythm in anaesthetized rats

Noxious somatic stimulation evokes respiratory and autonomic responses. The mechanisms underlying the responses and the manner in which they are co-ordinated are still unclear. The effects of activation of somatic nociceptive fibres on lumbar sympathetic nerve activity at slow (2-10 Hz) and fast frequency bands (100-1000 Hz) and the effects on respiratory-sympathetic coupling are unknown. In anaesthetized, artificially ventilated Sprague-Dawley rats under neuromuscular blockade, ensemble averaging of sympathetic activity following high-intensity single-pulse stimulation of the sciatic nerve revealed two peaks (~140 and ~250 ms) that were present at similar latencies whether or not slow or fast band filtering was used. Additionally, in the slow band of both lumbar and splanchnic sympathetic nerve activity, a third peak with a very slow latency (~650 ms) was apparent. In the respiratory system, activation of the sciatic nerve decreased the expiratory period when the stimulus occurred during the first half of expiration, but increased the expiratory period if the stimulus was delivered in the second half of the expiratory phase. The phase shifting of the respiratory cycle also impaired the respiratory-sympathetic coupling in both splanchnic and lumbar sympathetic nerve activity in the subsequent respiratory cycle. The findings suggest that noxious somatosympathetic responses reduce the co-ordination between respiration and perfusion by resetting the respiratory pattern generator.

A dog model to study ovary, ovarian ligament and visceral pain

ObjectiveA dog model was developed to study visceral pain by stimulating the ovarian ligament. Study designProspective experimental trial. AnimalsTwelve 1-year old female hound dogs weighing 25.7 ± 3.6 kg. MethodsDogs were anesthetized with sevoflurane. The right ovary was accessed via laparoscopy. A suture was placed around the ovarian ligament and exteriorized through the abdominal wall for stimulation. The noxious stimulus consisted of pulling the ovary and ovarian ligament with a force transducer. The response to noxious stimulation was determined using the anesthetic minimum alveolar concentration requirement (MAC) for sevoflurane. The ovarian MAC was compared to the standardized somatic noxious stimulation tail clamp MAC. The results are depicted as mean ± SD and corrected to sea-level. ResultsThe stimulus–response curve during ovarian stimulation in three dogs was hyperbolic and best represented by a three-parameter logistic growth curve model. The curve plateaued at 7.12 ± 4.19 N. From the stimulus-response curve, we chose 6.61 N to test the consistency and repeatability of the model in nine dogs. The ovarian stimulation MAC for sevoflurane in these dogs was 2.16 ± 0.46%. The ovarian stimulation confidence interval and limits are comparable to the results from tail stimulation MAC. The tail stimulation MACs before and after laparoscopy surgery were not different (1.86 ± 0.28% and 1.77 ± 0.38% respectively; p > 0.05) but lower when compared to the ovarian MAC (p < 0.01). The dogs recovered from anesthesia without complications. Conclusions and clinical relevanceThe ovarian stimulation model is an adequate and repeatable means of producing visceral stimulation to determine MAC. The model may provide a humane mechanism to study the effectiveness of analgesics for acute ovarian pain.

Sex differences in inflammation evoked by noxious chemical, heat and electrical stimulation

Neurogenic inflammation (NI) is a feature of several inflammatory pain conditions in which females are overrepresented. Therefore, we asked if there are sex differences in the inflammatory response evoked by well known neurogenic stimuli. We compared the amount of plasma extravasation (PE), a measure of inflammation, in the hindpaw skin of male and female rats caused by subcutaneous injection of capsaicin, application of noxious heat (51 °C water bath) or electrical stimulation of the saphenous nerve. We also compared the amount of PE in males and females evoked by substance P (SP), the principal neurogenic mediator of PE. PE was quantified using a video camera and digital image analysis to measure changes in reflectance (pixel intensity, PI) of skin due to accumulation of extravasated Evans blue (EB) dye. The increase in PI induced by capsaicin was significantly greater in females compared to males ( p < 0.001) and in estrus, diestrus, and metestrus females compared to proestrus females. The time to reach maximal capsaicin-induced PE was two times longer in estrus, diestrus, and metestrus females compared to males ( p < 0.05). PE induced by heat was also significantly greater in females compared to males ( p < 0.001), however, there was no sex-related difference in PE induced by electrical stimulation or by injection of SP. These findings show that females have a greater inflammatory response when inflammation is induced by capsaicin and noxious heat suggesting possible sex-related changes in TRPV-1 receptor mediated mechanisms. These results add to the growing list of sex difference responses to noxious somatic stimulation.

T1452 Predicting the Magnitude of Endogenous Visceral Pain Modulation Using Simple Noxious Visceral or Somatic Stimulation

T1452 Predicting the Magnitude of Endogenous Visceral Pain Modulation Using Simple Noxious Visceral or Somatic Stimulation

Midazolam inhibits cardiac nociception evoked by coronary artery occlusion in rats

This study was designed to investigate the potential existence of the response of neurons in the parafascicular nucleus of the thalamus to acute myocardial ischaemia induced by selective coronary artery occlusion and the effects of midazolam on the response in rats. The left anterior descending branch of the coronary artery was instrumented with a snare occluder in anaesthetized Sprague-Dawley rats. A single-barrel glass microelectrode was used for recording the unit discharges of the neuron in the parafascicular nucleus. The neuron responding only to noxious somatic stimulation was further examined for the response to coronary artery occlusion. Once the effect of coronary artery occlusion on the discharges was detected, the pharmacological effects of midazolam and flumazenil were examined. It was observed that the discharge rate of the neuron was markedly increased following coronary artery occlusion. Midazolam attenuated the increase in the discharges of the neuron induced by coronary artery occlusion (P < 0.05). The effect of midazolam was reversed by flumazenil. The parafascicular nucleus is involved in the modulation of cardiac nociception and midazolam possesses antinociceptive property in modulating cardiac pain.

Influence of peripheral nerve injury on response properties of locus coeruleus neurons and coeruleospinal antinociception in the rat

Noradrenergic locus coeruleus (LC) is involved in pain regulation. We studied whether response properties of LC neurons or coeruleospinal antinociception are changed 10–14 days following development of experimental neuropathy. Experiments were performed in spinal nerve–ligated, sham-operated and unoperated male rats under sodium pentobarbital anesthesia. Recordings of LC neurons indicated that responses evoked by noxious somatic stimulation were enhanced in nerve-injured animals, while the effects of nerve injury on spontaneous activity or the response to noxious visceral stimulation were not significant. Microinjection of glutamate into the central nucleus of the amygdala produced a dose-related inhibition of the discharge rate of LC neurons in nerve-injured animals but no significant effect on discharge rates in control groups. Assessment of the heat-induced hind limb withdrawal latency indicated that spinal antinociception induced by electrical stimulation of the LC was significantly weaker in nerve-injured than control animals. The results indicate that peripheral neuropathy induces bidirectional changes in coeruleospinal inhibition of pain. Increased responses of LC neurons to noxious somatic stimulation are likely to promote feedback inhibition of neuropathic hypersensitivity, while the enhanced inhibition of the LC from the amygdala is likely to suppress noradrenergic pain inhibition and promote neuropathic pain. It is proposed that the decreased spinal antinociception induced by direct stimulation of the LC may be explained by pronociceptive changes in the non-noradrenergic systems previously described in peripheral neuropathy. Furthermore, we propose the hypothesis that emotions processed by the amygdala enhance pain due to increased inhibition of the LC in peripheral neuropathy.

Influence of innocuous cervical vertebral movement on the efferent innervation of the adrenal gland in the rat

In general, in central nervous system intact anesthetized animals, adrenal sympathetic efferent nerve activity and catecholamine secretion increase in response to noxious somatic stimulation, and decrease in response to innocuous somatic stimulation. In anesthetized rats, noxious chemical stimulation of the thoracic and lumbar interspinous tissues is associated with large increases in adrenal sympathetic efferent nerve activity and catecholamine secretion, with a clear segmental organization to the reflex apparent in spinalized animals. However, the adrenal sympathetic nerve responses to mechanical stimulation in the form of pressure applied laterally to the lower thoracic and lower lumbar vertebrae do not display segmental organization, and the depressor response is more characteristic of responses to innocuous somatic stimulation despite the use of large forces (up to 3.0 kg). Therefore, we sought to determine whether innocuous movements of the mechanoreceptor-rich deep tissues of the neck modulate the sympathetic outflow to the adrenal gland. We performed experiments in 14 anaesthetised (Urethane 1 g/kg and Chloralose 0.1 g/kg) adult rats. Rats were intubated and breathed spontaneously. A computer driven small animal manipulator was used to impose ramp and hold rotational displacements (12°/s, hold duration 2 s) of the 2nd cervical vertebra (range 2–30°) while recording multi-unit activity from sympathetic nerves innervating the adrenal gland. While noxious forepaw pinch elicited an increase in sympathetic nerve activity to the adrenal gland, there was no significant change in sympathetic nerve activity with small (2° or 6°) rotations. Significant changes ( P < 0.05) in sympathetic activity were observed in only 7% ( n = 21) of all trials at larger displacements (12°, 20°, 25°, 30° n = 287 trials). Our data suggest that although noxious stimuli may modulate sympathetic outflow, it is rare for afferents signalling innocuous cervical vertebral movements to modulate sympathetic nerves innervating the adrenal gland.

Anesthetic effects on the thalamus, reticular formation and related systems

Anesthetics are used extensively clinically and in research. However, the mechanisms by which anesthetics act to produce the desired end-points of unconsciousness, amnesia and immobility are only beginning to be understood. Recent evidence indicates that the immobilizing effect of anesthetics occurs largely in the spinal cord, whereas it is assumed that the sedative and amnesic actions occur in the brain. Our recent studies, however, indicate that anesthetics exert an indirect, spinal effect on reticulo-thalamo-cortical mechanisms of arousal and, thus, might affect consciousness and memory. These data are consistent with reports of reduced anesthetic requirements for sedation during neuroaxial blockade by spinal anesthesia. The presumed mechanism is decreased afferent impulses to the brain, which reduces arousal and, thereby, reduces sedative requirements. We have used the complementary approaches of single-unit recording and intracranial electrical stimulation to investigate the effects of a common inhaled anesthetic, isoflurane, on reticulo-thalamo-cortical arousal in a goat preparation. The excitatory responses of single neurons in the midbrain reticular formation (MRF) to noxious somatic stimulation are significantly attenuated when the concentration of systemically delivered isoflurane was increased above 1 MAC (the minimum alveolar concentration required to prevent coordinated movement in response to a noxious stimulus), in parallel with a loss of stimulus-evoked desynchronization of the cortical electroencephalogram (EEG). Part of this depressant effect is mediated indirectly in the spinal cord because selectively reducing the concentration of isoflurane delivered differentially to the spinal cord enhances MRF neuronal responses and cortical arousal. In goats anesthetized with isoflurane at ∼1 MAC, electrical stimulation at distinct sites, including the MRF, peduncolopontine tegmentum (PTT), and medial/intralaminar thalamus, elicits desynchronization of the cortical EEG. Increasing the concentration of isoflurane above 1 MAC abolished this effect. In goats prepared for differential delivery of anesthetic to the cranial and torso (spinal) circulations, electrical stimulation in the medial thalamus elicits greater cortical desynchronization at lower currents when the concentration of isoflurane delivered to the spinal cord is reduced while maintaining the cranial isoflurane concentration ≥1 MAC. These results indicate that the depressant effect of isoflurane anesthesia on spinal somatosensory transmission indirectly influences the threshold for reticulo-thalamo-cortical arousal.

Gerard W. Ostheimer “What’s New in Obstetric Anesthesia” Lecture

Gerard W. Ostheimer “What’s New in Obstetric Anesthesia” Lecture

Acupuncture inhibition on neuronal activity of spinal dorsal horn induced by noxious colorectal distention in rat

To observe how acupuncture stimulation influences the visceral nociception in rat and to clarify the interactions between acupuncture or somatic input and visceral nociceptive inputs in the spinal dorsal horn. These will provide scientific base for illustrating the mechanism of acupuncture on visceral pain. Experiments were performed on Sprague-Dawley rats and the visceral nociceptive stimulus was generated by colorectal distention (CRD). Unit discharges from individual single neuron were recorded extracellularly with glass-microelectrode in L(1-3) spinal dorsal horn. Acupuncture stimulation was applied at contralateral heterotopic acupoint and ipsilateral homotopic acupoint, both of which were innervated by the same segments that innervate also the colorectal-gut. The visceral nociception could be inhibited at the spinal level by the heterotopic somatic mechanical stimulation and acupuncture. The maximal inhibition was induced by acupuncture or the somatic noxious stimulation at spinal dorsal horn level with inhibiting rate of 68.61% and 60.79%, respectively (P<0.01 and <0.001). In reversible spinalized rats (cervical-thoracic cold block) both spontaneous activity and responses to CRD increased significantly in 16/20 units examined, indicating the existence of tonic descending inhibition. The inhibition of acupuncture on the noxious CRD disappeared totally in the reversible spinalized rats (P<0.001). The inputs of noxious CRD and acupuncture may interact at the spinal level. The nociceptive visceral inputs could be inhibited by acupuncture applied to hetero-topic acupoint. The effect indicates that the spinal dorsal horn plays a significant role in mediating the inhibition of acupuncture and somatic stimulation on the neuronal response to the noxious visceral stimulation and the inhibition is modulated by upper cervical cord and/or supra-spinal center.

Nociception attenuates parasympathetic but not sympathetic baroreflex via NK1 receptors in the rat nucleus tractus solitarii.

Somatic noxious stimulation can evoke profound cardiovascular responses by altering activity in the autonomic nervous system. This noxious stimulation attenuates the cardiac vagal baroreflex, a key cardiovascular homeostatic reflex. This attenuation is mediated via NK1 receptors expressed on GABAergic interneurones within the nucleus of the solitary tract (NTS). We have investigated the effect of noxious stimulation and exogenous substance P (SP) on the sympathetic component of the baroreflex. We recorded from the sympathetic chain in a decerebrate, artificially perfused rat preparation. Noxious hindlimb pinch was without effect on the sympathetic baroreflex although the cardiac vagal baroreflex gain was decreased (56 %, P < 0.01). Bilateral NTS microinjection of SP (500 fmol) produced a similar selective attenuation of the cardiac vagal baroreflex gain (62 %, P < 0.005) without effect on the sympathetic baroreflex. Recordings from the cardiac sympathetic and vagal nerves confirmed the selectivity of the SP inhibition. Control experiments using a GABAA receptor agonist, isoguvacine, indicated that both components of the baroreflex (parasympathetic and sympathetic) could be blocked from the NTS injection site. The NTS microinjection of a NK1 antagonist (CP-99,994) in vivo attenuated the tachycardic response to hindlimb pinch. Our data suggest that noxious pinch releases SP within the NTS to selectively attenuate the cardiac vagal, but not the sympathetic, component of the baroreflex. This selective withdrawal of the cardiac vagal baroreflex seems to underlie the pinch-evoked tachycardia seen in vivo. Further, these findings confirm that baroreflex sympathetic and parasympathetic pathways diverge, and can be independently controlled, within the NTS.

Fos expression in tyrosine hydroxylase-containing neurons in rat brainstem after visceral noxious stimulation: an immunohistochemical study.

To prove that neurons in the different structures of the brainstem that express tyrosine hydroxylase (TH) are involved in the transmission and modulation of visceral or somatic nociceptive information in rat. Immunohistochemical double-staining method was used to co-localize TH and Fos expression in neurons of the rat brainstem in visceral or subcutaneous noxious stimulation models. Neurons co-expressing TH/Fos were observed in lateral reticular nucleus (LRT), rostroventrolateral reticular nucleus (RVL), solitary tract nucleus (SOL), locus coeruleus (LC), A5, A7 neuronal groups and ventrolateral subdivision of the periaqueductal gray (vlPAG) in both models. But the proportion and number of the double-labeled neurons responding to the two noxious stimuli were significantly different in the LRT, RVL and LC nuclei. The proportion and number of the TH/Fos double-labeled neurons in the visceral pain model were smaller than that in the subcutaneous pain model. However, in the case of SOL, they were similar in the two models. Differences of Fos expression in TH immunoreactive neurons in animals after visceral and somatic noxious stimulation indicate that the mechanisms of the transmission and modulation of visceral nociceptive information in the brainstem may be different from that of somatic nociceptive information.

The nucleus of the solitary tract: an integrating station for nociceptive and cardiorespiratory afferents.

Painful stimuli can evoke dramatic responses in the cardiovascular and respiratory systems. We have assessed the role of both the sympathetic and parasympathetic nervous system in mediating the reflex tachycardia that accompanies somatic nociception. We describe a major role for the nucleus tractus solitarii (NTS) as a site for integrating nociceptive and cardiorespiratory afferents. Since cardiorespiratory and nociceptive afferents terminate in the NTS, this nucleus offers a powerful opportunity for central modulation. We show that the NTS plays a major role in mediating the reflex tachycardia evoked by somatic noxious stimulation. Similar noxious stimulation attenuates the cardiac component of the peripheral chemoreceptor reflex and inhibits the peripheral chemoreceptor-evoked excitatory synaptic response of some NTS neurones. The functional interpretation we propose is that by depressing homeostatic reflexes at the NTS, noxious stimulation-evoked cardiorespiratory changes can be expressed and maintained, which may be essential for the survival of the animal.

Nociceptive afferents selectively modulate the cardiac component of the peripheral chemoreceptor reflex via actions within the solitary tract nucleus

Our previous findings showed that the nucleus of the solitary tract (NTS) mediated part of the tachycardia evoked during somatic noxious stimulation. Here, we investigated the interaction between somatic nociceptor- and peripheral chemoreceptor-evoked cardiac changes. We sought to determine whether this interaction occurred within the NTS, the primary site of termination of chemoreceptor afferents. In a working heart–brainstem preparation of rat, mechanical noxious activation of a forelimb evoked a tachycardia of 17.5±3 (mean±S.E.M.) b.p.m., whereas sodium cyanide (7–30 μg) stimulation of peripheral chemoreceptors produced a sub-maximal bradycardia of −140±15 b.p.m. During nociceptor stimulation the sodium cyanide-evoked bradycardia was attenuated to −42.6±12 b.p.m. but could be prevented by a multiple bilateral NTS microinjection of bicuculline (i.e. −173±18 b.p.m.). Furthermore, the activity of NTS neurones responding to peripheral chemoreceptor stimulation increased from 2.8±1.3 to 9.4±1.9 Hz during sodium cyanide injection ( n=7; P<0.01). The latter response was attenuated reversibly to 2.9±0.9 Hz during simultaneous stimulation of the brachial nerve. Pressure ejection of bicuculline abolished this inhibitory action of brachial-nerve stimulation on the chemoreceptor-evoked excitatory synaptic response. We conclude that somatic noxious stimulation attenuates the chemoreceptor reflex-evoked bradycardia via a GABA Aergic mechanism in the NTS.

Inhalation anesthetics suppress the expression of c-Fos protein evoked by noxious somatic stimulation in the deeper layer of the spinal cord in the rat

The effects of inhalation anesthetics, nitrous oxide (N 2O) and halothane, on the expression of c-Fos protein evoked by formalin injection were studied in the spinal cord in the rat. The expression of c-Fos protein was detected by immunocytochemistry following the injection of formalin (5%, 100 μl) into the plantar surface of the left hindpaw. After 15 min of halothane (F) anesthesia, the anesthetics was switched to 40% or 70% of N 2O, 0.5% or 1.5% of F or room air (for control) immediately following the formalin injection. Two hours later the rats were sacrificed and perfused. Sections of the L4 level of spinal cord were immunostained with anti c-Fos antibody. We counted the number of Fos-like immunoreactive (FLI) cells in every specific lamina as follows; superficial layer (laminae I and II), nucleus proprius (laminae III and IV), neck of the dorsal horn (laminae V and VI) and ventral gray (laminae VII–X). Then we compared the results of each category of sample. Both N 2O and halothane suppressed the expression of c-Fos in the neck of the dorsal horn and ventral gray in a dose-dependent manner, but no effects were seen at the superficial layer or nucleus proprius. Suppression of c-Fos expression was greater under N 2O than halothane anesthesia. This finding suggests that N 2O had a stronger analgesic effect than halothane. The current study indicates that inhalation anesthetics do not act equally on every kind of spinal neurons. Both N 2O and halothane have effects on spinal neurons in the deeper layers but not on the neurons existed in laminae I–II, some of which directly receive noxious inputs. Pretreatment with 2 mg/kg of naloxone, which completely reversed the effects of morphine, did not alter the effect of 70%N 2O, suggesting that the analgesic effect of N 2O is not mediated by an intrinsic opioid mechanism at the spinal cord level. ©1977 Elsevier Science B.V. All rights reserved.

Estrous and sex variations in vocalization thresholds to hindpaw and tail pressure stimulation in the rat

This study examined sex and estrous differences in vocalization thresholds of rats to hindpaw and tail pressure stimulation tested daily throughout at least 3 weeks. When all the measures were pooled, compared to males, female rats had higher thresholds for tail pressure (499 ± 6 g, n = 188 measures vs. 466 ± 2 g, n = 144 measures, respectively), but equal thresholds for hindpaw pressure (321 ± 6 g n = 188 measures vs. 319 ± 2 g, n = 144 measures, respectively). Thresholds of female rats in proestrus and estrus were lower than those of rats in metestrus and diestrus for both tail and hindpaw stimulation, whereas those of males did not vary systematically. Thresholds at the two stimulation sites covaried in females but not in males. These results add to the growing list of important interacting factors that underly behavioral sensitivity to noxious somatic stimulation.

Contributions of anterior cingulate cortex to behaviour.

Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of morphine on neuronal and behavioural responses to visceral and somatic nociception at the level of sinal cord

This study was undertaken to examine the role of morphine in modulation of nociception in visceral and somatic pain tests at the level of the spinal cord, using neurophysiological and behavioural reflex assays. In the neurophysiological study, we recorded extracellularly the activity of the single viscero-somatic convergent neurons of the spinal dorsal horn, which was evoked by the colorectal distention (80 mmHg) of noxious visceral stimulation and the radiant heat (51 degrees C) of noxious somatic stimulation, in decerebrated, spinally transected cats. Spinally administered morphine (200 micrograms) produced significant suppression of noxiously evoked activity by both stimuli in a time-dependent manner. In addition, intravenously administered naloxone reversed the suppressive effects of morphine. In the behavioral reflex study, colorectal distension threshold and tail-flick latency were measured in rats chronically implanted with lumbar intrathecal catheter. Intrathecally administered morphine significantly elevated the colorectal distension threshold and prolonged the tail-flick latency in a time- and dose-dependent manner. The results of the present study demonstrated that spinal morphine was capable of suppressing the evoked activity of the viscero-somatic convergent neurons, resulting in suppression visceral and somatic pain behavioral reflexes.