Noxious Somatic Stimuli Research Articles

Contactless Assessment of Cerebral Autoregulation by Photoplethysmographic Imaging at Green Illumination.

Accurate and practical assessment of the brain circulation is needed to adequately estimate the viability of cerebral blood flow regulatory mechanisms in various physiological conditions. The objective of our study was to examine feasibility of the contactless green-light imaging photoplethysmography (PPG) for assessing cerebral autoregulation by revealing the dynamic relationships between cortical microcirculation assessed by PPG and changes in systemic blood pressure caused by visceral and somatic peripheral stimuli. In anesthetized male Wistar rats, the PPG video images of the open parietal cortex (either with unimpaired or dissected dura mater), electrocardiogram, and systemic arterial blood pressure (ABP) in the femoral artery were continuously recorded before, during and after visceral (colorectal distension) or somatic (tail squeezing) stimulation. In the vast majority of experiments with intact and removed dura mater, both spontaneous and peripheral stimulation-evoked changes in ABP negatively correlated with the accompanying alterations in the amplitude of pulsatile PPG component (APC), i.e., an increase of ABP resulted in a decrease of APC and vice versa. The most pronounced ABP and APC alterations were induced by noxious stimuli. Visceral painful stimulation in all cases caused short-term hypotension with simultaneous increase in cortical APC, whereas somatic noxious stimuli in 8 of 21 trials produced hypertensive effect with decreased APC. Animals with pressure 50-70 mmHg possessed higher negative cerebrovascular response rate of ABP-APC gradients than rats with either lower or higher pressure. Severe hypotension reversed the negative ratio to positive one, which was especially evident under visceral pain stimulation. Amplitude of the pulsatile PPG component probably reflects the regulation of vascular tone of cerebral cortex in response to systemic blood pressure fluctuations. When combined with different kinds of peripheral stimuli, the technique is capable for evaluation of normal and elucidation of impaired cerebrovascular system reactivity to particular physiological events, for example pain. The reported contactless PPG monitoring of cortical circulatory dynamics during neurosurgical interventions in combination with recordings of changes in other physiological parameters, such as systemic blood pressure and ECG, has the appealing potential to monitor viability of the cortex vessels and determine the state of patient’s cerebrovascular autoregulation.

Differential responses of neurons in the rat caudal ventrolateral medulla to visceral and somatic noxious stimuli and their alterations in colitis

Visceral and somatic types of pain have been reported to manifest crucial differences not only in the experience, but also in their peripheral and central processing. However, the precise neuronal mechanisms that responsible for the modality-specific transmission of pain signals, especially at the supraspinal level, remain unclear. Very little is known also about the potential involvement of such mechanisms in the development of viscero-somatic hyperalgesia. Therefore, in the present study performed on urethane-anesthetized adult male Wistar rats we examined responses of neurons in the caudal ventrolateral medulla (CVLM)—the first site for supraspinal processing of both internal and external pain signals—to visceral (colorectal distension, CRD) and somatic (squeezing of the tail) noxious stimulations and evaluated alterations in response properties of these cells after the induction of colitis. It has been found out that the CVLM of healthy control rats, along with harboring of cells excited by both stimulations (23.7%), contained neurons that were activated by either visceral (31.9%) or somatic noxious stimuli (44.4%). In inflamed animals, the percentages of the visceral and somatic nociceptive cells were decreased (to 18.3% and 34.3%, correspondingly) and the number of bimodal neurons was increased (up to 47.4%); these alterations were associated with substantially enhanced responses of both the modality-specific and convergent CVLM neurons not only to CRD, but also to squeezing of the tail. Under these conditions, visceral and somatic pain stimuli induced similar changes in arterial blood pressure and respiratory rate, whereas in the absence of intestinal inflammation noxious CRD and tail stimulation evoked predominantly divergent autonomic reactions. The data obtained can benefit to a deeper understanding of the neuronal mechanisms that underlie differential supraspinal processing of visceral and somatic noxious stimuli and can potentially contribute to the realization of specific cardiovascular and respiratory accompaniments inherent to a particular type of pain. Therewith, results of the study elucidate colitis-induced alterations in these mechanisms, which may be responsible for the combined development of visceral hypersensitivity and somatic hyperalgesia.

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.

An Endogenous Pain Control System is Altered in Subjects with Interstitial Cystitis

Multiple studies have demonstrated that in healthy subjects, painful stimuli applied to one part of the body inhibit pain sensation in other parts of the body, a phenomenon referred to as conditioned pain modulation. Conditioned pain modulation is related to the presence of endogenous pain control systems. Studies have demonstrated deficits in conditioned pain modulation associated inhibition in many but not all chronic pain disorders. In this study we determine whether conditioned pain modulation is altered in subjects with interstitial cystitis/bladder pain syndrome. Female subjects with and without the diagnosis of interstitial cystitis/bladder pain syndrome were studied psychophysically using quantitative cutaneous thermal, forearm ischemia and ice water immersion tests. Conditioned pain modulation was assessed by quantifying the effects of immersion of the hand in ice water (conditioning stimulus) on threshold and tolerance of cutaneous heat pain (test stimulus) applied to the contralateral lower extremity. The conditioned pain modulation responses of the subjects with interstitial cystitis/bladder pain syndrome were statistically different from those of healthy control subjects for cutaneous thermal threshold and tolerance measures. Healthy control subjects demonstrated statistically significant increases in thermal pain tolerance whereas subjects with the diagnosis of interstitial cystitis/bladder pain syndrome demonstrated statistically significant reductions in thermal pain tolerance. An endogenous pain inhibitory system normally observed with conditioned pain modulation was altered in subjects with interstitial cystitis/bladder pain syndrome. This finding identifies interstitial cystitis/bladder pain syndrome as similar to several other chronic pain disorders such as fibromyalgia and irritable bowel syndrome, and suggests that a deficit in endogenous pain inhibitory systems may contribute to such chronic pain disorders.

Neurophysiology and Intraoperative Nociception

Neurophysiology and Intraoperative Nociception

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.

Pregabalin modulation of spinal and brainstem visceral nociceptive processing

Brainstem and spinal mechanisms mediating visceral nociception are investigated here using electrophysiology and immunohistochemistry techniques in a model of acute visceral pain. Colorectal distension (CRD) produced graded visceromotor responses (VMR) in normal rats, and these were facilitated by intracolonic mustard oil (MO) that generated acute visceral hyperalgesia. The neuropathic pain drug pregabalin (PGB) is thought to have state-dependent effects in attenuating neuropathic, but not acute somatic pain, likely by impairing calcium-channel trafficking. We found that systemic PGB produced antinociceptive effects on CRD-evoked VMRs in naïve rats lacking pathophysiology and in MO-pretreated rats. Systemic PGB also significantly reduced Fos labelling in lumbosacral spinal cords of rats given noxious repetitive CRD; however, PGB did not alter this measure of neural activity in the brainstem. Differential brainstem processing of noxious somatic and visceral stimuli may underlie the unique lack of state-dependent actions of PGB in this visceral pain model. Single-unit recordings in the rostral ventromedial medulla (RVM) verify that brainstem processing of somatic and visceral stimuli differs. The effects of CRD on RVM cells classed as ON, OFF, or NEUTRAL were independent of their somatic responses, with surprising changes in RVM cell activity to innocuous visceral stimulation. PGB also markedly reduced the visceral responses of RVM ON-cells to noxious CRD. These results illustrate clear differences in the central processing of visceral and somatic stimuli, yet a common role for descending modulation by brainstem activity in mediating evoked pain measures.

Role of ATP in the Mechanisms Underlying Intestinal Afferent Sensitivity to Hydrogen Sulphide

the 3rd CRD, 24 h after the last WAS (day 5). The VMR to CRD after WAS was expressed as percentage of the respective baseline values at different pressures of CRD. Data were analyzed using two-way ANOVA followed by a multiple comparison Bonferroni post-hoc test. Results: Immediately after the 1h exposure to WAS, on day 4, non-injected male and female rats exhibited visceral analgesia at 40 mmHg (p<0.05). Saline or naloxone injected sc before each WAS enhanced the visceral analgesia in both sexes in comparison to noninjected rats (analgesic response at 40 and 60 mmHg). On day 5, 24h after the last session of stress, the VMR was back to baseline values in all non-injected and injected male and female rats, except in females injected with naloxone which exhibited an analgesia at 60 mmHg (74.8±11.9 vs 100.0±0.0 %, p<0.05). Conclusions:When monitored non-invasively, intermittent repeated exposure to a psychological stress induces an immediate naloxoneindependent visceral analgesia in male and female rats. Repeated sc injections potentiate the immediate analgesic response suggesting that the concomitant somatic noxious stimuli may exert heterotopic analgesic effects. The sex-dependent delayed restoration of the VMR to baseline values by naloxone indicates an opioid-dependent component in females' stressinduced visceral response. Supported by NIH P50 DK-64539, The Kosciuszko Foundation (AM) and Wonkwang University (YSK) *ML, AM equal contribution

A Functional Magnetic Resonance Imaging (FMRI) Scanning Environment Enhances Visceral Pain in Patients With Irritable Bowel Syndrome (IBS)

the 3rd CRD, 24 h after the last WAS (day 5). The VMR to CRD after WAS was expressed as percentage of the respective baseline values at different pressures of CRD. Data were analyzed using two-way ANOVA followed by a multiple comparison Bonferroni post-hoc test. Results: Immediately after the 1h exposure to WAS, on day 4, non-injected male and female rats exhibited visceral analgesia at 40 mmHg (p<0.05). Saline or naloxone injected sc before each WAS enhanced the visceral analgesia in both sexes in comparison to noninjected rats (analgesic response at 40 and 60 mmHg). On day 5, 24h after the last session of stress, the VMR was back to baseline values in all non-injected and injected male and female rats, except in females injected with naloxone which exhibited an analgesia at 60 mmHg (74.8±11.9 vs 100.0±0.0 %, p<0.05). Conclusions:When monitored non-invasively, intermittent repeated exposure to a psychological stress induces an immediate naloxoneindependent visceral analgesia in male and female rats. Repeated sc injections potentiate the immediate analgesic response suggesting that the concomitant somatic noxious stimuli may exert heterotopic analgesic effects. The sex-dependent delayed restoration of the VMR to baseline values by naloxone indicates an opioid-dependent component in females' stressinduced visceral response. Supported by NIH P50 DK-64539, The Kosciuszko Foundation (AM) and Wonkwang University (YSK) *ML, AM equal contribution

TRP Channels-Mediated Intestinal Afferent Sensitivity to Hydrogen Sulphide

the 3rd CRD, 24 h after the last WAS (day 5). The VMR to CRD after WAS was expressed as percentage of the respective baseline values at different pressures of CRD. Data were analyzed using two-way ANOVA followed by a multiple comparison Bonferroni post-hoc test. Results: Immediately after the 1h exposure to WAS, on day 4, non-injected male and female rats exhibited visceral analgesia at 40 mmHg (p<0.05). Saline or naloxone injected sc before each WAS enhanced the visceral analgesia in both sexes in comparison to noninjected rats (analgesic response at 40 and 60 mmHg). On day 5, 24h after the last session of stress, the VMR was back to baseline values in all non-injected and injected male and female rats, except in females injected with naloxone which exhibited an analgesia at 60 mmHg (74.8±11.9 vs 100.0±0.0 %, p<0.05). Conclusions:When monitored non-invasively, intermittent repeated exposure to a psychological stress induces an immediate naloxoneindependent visceral analgesia in male and female rats. Repeated sc injections potentiate the immediate analgesic response suggesting that the concomitant somatic noxious stimuli may exert heterotopic analgesic effects. The sex-dependent delayed restoration of the VMR to baseline values by naloxone indicates an opioid-dependent component in females' stressinduced visceral response. Supported by NIH P50 DK-64539, The Kosciuszko Foundation (AM) and Wonkwang University (YSK) *ML, AM equal contribution

Central Processing of Noxious Somatic Stimuli in Patients With Irritable Bowel Syndrome Compared With Healthy Controls

To compare a central analgesic mechanism known as diffuse noxious inhibitory controls (DNIC) using somatic test stimuli and somatic conditioning stimuli, (CS) in irritable bowel syndrome (IBS) patients and healthy controls. Participants were 48 premenopausal females (27 with IBS), mean age of 29 years. The phasic heat test stimulus (peak temperature, 50 degrees C) was applied to the left palm. The DNIC effect, which measured reductions in average pain ratings (APR) during counter irritation (submersion of the participant's right hand in painful 12 degrees C circulating water) compared with baseline, was compared between groups. In addition, a second, counterbalanced, CS protocol (right hand submerged in nonpainful 32 degrees C circulating water) was performed. Differences in APR between the 2 counterirritation protocols were compared between groups to control for nonspecific effects known to influence DNIC. Psychologic measures and cardiovascular reactivity were also assessed. IBS patients demonstrated smaller DNIC than controls (P=0.011, repeated measures analysis of variance), and greater state-anxiety, depression, catastrophizing, and anger-out expression (P<0.05). Group differences in DNIC were enhanced after controlling for nonspecific effects occurring during the nonpainful CS, and for psychologic measures (P=0.001, repeated measures analysis of covariance). There were no group differences in age, cardiovascular reactivity, APR, or pain ratings for the 12 degrees C CS. These data demonstrate deficient DNIC in IBS. This is the first study to adequately control for alternative explanations of pain reduction during counterirritation. Only by controlling for nonspecific effects can evidence of deficient DNIC be attributed to dysregulation in endogenous analgesic mechanisms.

Central and peripheral hypersensitivity in the irritable bowel syndrome

Previous investigations of somatic hypersensitivity in IBS patients have typically involved only a single stimulus modality, and little information exists regarding whether patterns of somatic pain perception vary across stimulus modalities within a group of patients with IBS. Therefore, the current study was designed to characterize differences in perceptual responses to a battery of noxious somatic stimuli in IBS patients compared to controls. A total of 78 diarrhea-predominant and 57 controls participated in the study. We evaluated pain threshold and tolerance and sensory and affective ratings of contact thermal, mechanical pressure, ischemic stimuli, and cold pressor stimuli. In addition to assessing perceptual responses, we also evaluated differences in neuroendocrine and cardiovascular responses to these experimental somatic pain stimuli. A subset of IBS patients demonstrated the presence of somatic hypersensitivity to thermal, ischemic, and cold pressor nociceptive stimuli. The somatic hypersensitivity in IBS patients was somatotopically organized in that the lower extremities that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. There were also changes in ACTH, cortisol, and systolic blood pressure in response to the ischemic pain testing in IBS patients when compared to controls. The results of this study suggest that a more widespread alteration in central pain processing in a subset of IBS patients may be present as they display hypersensitivity to heat, ischemic, and cold pressor stimuli.

Central Processing of Noxious Somatic Stimuli in Patients With Irritable Bowel Syndrome Compared With Healthy Controls

Central Processing of Noxious Somatic Stimuli in Patients With Irritable Bowel Syndrome Compared With Healthy Controls

Spinal coadministration of ketamine reduces the development of tolerance to visceral as well as somatic antinociception during spinal morphine infusion.

This study was designed to investigate the effects of ketamine, an N-methyl-D-aspartate receptor antagonist, on the development of tolerance to morphine and morphine antinociception during intrathecal infusion. Two intrathecal catheters were implanted in the subarachnoid space in male rats under pentobarbital anesthesia. One catheter was used for the intrathecal infusion with the following solutions: morphine 1 microg x kg(-1) x hr(-1)(M1) and 5 microg x kg(-1) x hr(-1) (M5);ketamine 250 microg x kg(-1) x hr(-1) (K250); morphine plus ketamine, 1 microg x kg(-1) x hr(-1) plus 250 microg x kg(-1) x hr(-1) (M1 + K250) and 5 microg x kg(-1) x hr(-1) + 250 microg x kg(-1) x hr(-1) (M5 + K250); or saline. The other catheter was used for morphine challenge tests. The responses to noxious somatic and visceral stimuli were measured by tail flick (TF) and colorectal distension (CD) tests, respectively. Measurements were performed once a day for 7 days. Challenge tests with intrathecal morphine were performed to assess the magnitude of tolerance on Day 5 and Day 7. The antinociceptive effect was evaluated by using the percent of maximal possible effect (%MPE). Morphine infusion produced significant increases in %MPEs in TF and CD tests, while the saline and K250 infusions did not show any changes. The M1 + K250 infusion significantly increased the %MPEs in TF and CD tests, although the M1 and K250 infusions alone showed no changes. M5 + K250 enhanced the increases of %MPEs in TF and CD tests compared with the M5 infusion alone. In the challenge tests, the M1 + K250 infusion showed no significant decrease in %MPEs and TF and CD tests. The M5 + K250 infusion significantly inhibited those decreases in %MPEs, although the M5 infusion showed significant decreases in TF and CD tests. We concluded that ketamine attenuated the development of morphine tolerance to antinociceptive effects and increased the somatic and visceral antinociception of morphine. Intrathecally coinfused ketamine attenuated morphine tolerance to somatic and visceral antinociception and increased morphine antinociception at the spinal level. These results suggest that a combination of morphine with ketamine may have an advantage in long-term use of opioids for controlling visceral as well as somatic pain.

Intrathecal treatment with MK-801 suppresses thermal nociceptive responses and prevents c-fos immunoreactivity induced in rat lumbar spinal cord neurons

Sensitization of the second order neurons in the spinal dorsal horn after somatic noxious stimuli is partly mediated by the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor. These neurons also express c-Fos immunoreactivity in response to the somatic noxious stimuli. The present study assessed the inifluence of intrathecal pre-treatment with MK-801, a non-competitive antagonist of NMDA receptor, on thermal sensitization following peripheral noxious heat stimulation. In addition, the influence of MK-801 on c-Fos immunoreactivity in the rat lumbar spinal cord neurons after the peripheral noxious heat was examined. Sprague-Dawley rats were subject to intrathecal catheterization and administration of MK-801 or saline before and after noxious heat (52° C) stimulation of rat hind paws. Thermal sensitization was tested after MK-801 (0.1 μmol 10 μl–1). Fos-like immunoreactivity was evaluated 2 h after noxious stimulation in a separate group of animals. MK-801 significantly increased the thermal withdrawal threshold by 60% following noxious heat stimulation and reduced c-Fos immunoreactivity in the second order neurons by 70% in the dorsal horn. The study suggests that glutamate plays a pivotal role in the thermal nociceptive pathway and indicates that the NMDA receptor is necessary to maintain normal thermal sensitization, possibly by regulating c-fos gene expression in second order neurons. [Neurol Res 1999; 21: 593–598]

Viscerosomatic interactions in the thalamic ventral posterolateral nucleus (VPL) of the squirrel monkey

In anesthetized squirrel monkeys single cell recordings were performed using tungsten microelectrodes. The responses of 29 viscerosomatoceptive and somatoceptive VPL neurons to noxious distension of the urinary bladder, the lower esophagus and the distal colon and to innocuous and noxious somatic stimuli were assessed when these stimuli were presented separately or together. Neuronal responses were defined as additive or interactive depending on the relative changes in responses to individual somatic or visceral stimuli, and on their responses during conditioning (somatic and visceral stimuli applied concurrently). In 13 neurons interactions between the somatosensory and visceral inputs could be demonstrated. The dominant interactive effect was inhibition, although facilitatory effects were seen as well (2 of 13). The magnitude or direction of the interactions seemed independent of the location of the somatic and visceral receptive fields. The mean population response of the neurons showing interactions was 4.66 spikes/s to somatic stimulation, and 0.07 spikes/s to visceral stimulation. During conditioning the mean interactive effect was −62% of the calculated additive effect. This implies that overall the somatic responses are halved during a coincident visceral stimulus. In a subgroup of the VPL neurons, which were classified as pure somatic responsive ( n=14) due to their unresponsiveness during visceral stimulation alone, a third ( n=5) still exhibited visceral convergence during conditioning. The latter neurons, therefore, receive visceral inputs, which function in a purely interactive (modulatory) manner. It is concluded that part of the described effects is due to competition (cross modality suppression) between the visceral and somatic inputs. We further conclude that the suppression of somatic information by noxious visceral stimuli may contribute to a more effective processing of the discriminatory aspects of nociceptive visceral information previously demonstrated in VPL.

Minimum alveolar anesthetic concentrations for airway occlusion in cats: a new concept of minimum alveolar anesthetic concentration-airway occlusion response.

Minimum alveolar anesthetic concentration (MAC) is defined as an end-tidal concentration of inhaled anesthetic required to prevent purposeful movement (positive motor response) in 50% of subjects to somatic noxious stimuli. Although MAC for visceral noxious stimuli has not been well investigated, airway occlusion can be a noxious respiratory stimulus that can induce a visceral sensation of choking. In this study, MAC for airway occlusion (MAC-AOR) was determined during halothane, isoflurane, and sevoflurane anesthesia and compared with the MAC values for somatic noxious stimuli such as toe pinch (MAC-pinch) or tetanic stimulus (MAC-tetanus) in cats. Thirty-four adult cats were used. In 24 cats, the motor responses to three different stimuli (toe pinch, tetanic stimulus, and airway occlusion for 6 min) were observed during inhaled anesthesia and rated as positive or negative. The concentration of an inhaled anesthetic was changed in steps of 0.1%-0.2 vol% until the bracketing procedure (i.e., the highest concentration of inhaled anesthetic permitting a positive motor response and the lowest concentration preventing the response were determined) was completed. In 10 cats, the effect of anesthetic duration on MAC-AOR was also investigated. Each mean MAC (MAC-pinch, MAC-AOR, and MAC-tetanus, respectively) was as follows: halothane 0.99, 1.13, and 1.46; isoflurane 1.50, 1.65, and 2.22; and sevoflurane 3.07, 3.38, and 3.95. The first and last MAC-AOR values determined during 6-h halothane anesthesia were 1.10 and 1.11, respectively. In conclusion, airway occlusion can be a noxious stimulus and can induce an all-or-none type of motor response, depending on the depth of inhalational anesthesia in cats. This phenomenon can permit the introduction a new concept of MAC-AOR. Airway occlusion can be a noxious visceral stimulus and induce all-or-none type of motor response in cats, depending on the depth of inhalational anesthesia. This permits the introduction of a new concept of minimum alveolar anesthetic concentration airway occlusion response.

Antinociceptive interaction of intrathecal alpha2-adrenergic agonists, tizanidine and clonidine, with lidocaine in rats.

The intrathecal alpha2-adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia. The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2-adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine. Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2-adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored. Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in microg) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure. The authors' results show that intrathecal tizanidine and clonidine synergistically interact with lidocaine so that the degree of antinociception to somatic noxious stimuli are enhanced. The antinociceptive synergistic interaction between tizanidine and lidocaine may be useful in clinical practice without affecting blood pressure, heart rate, or motor function.

Effects of remote deep somatic noxious stimuli on a jaw reflex in man

The effects on an inhibitory jaw reflex of activating deep somatic afferent nerves in a remote part of the body (the arm) were studied in 13 humans. Electromyographic recordings were made from the active masseter of the long-latency (mean 42.0 ± 1.1 ms) inhibitory reflex evoked by electrical stimulation of the upper lip. Immediately after a 1-min conditioning period during which the participants compressed a hand-held spring once a second while ischaemia was produced in the arm with an inflated pneumatic cuff, the magnitude of the inhibitory reflex decreased significantly (by 43%). The reflex recovered within 5 min to a magnitude that was not significantly different from its pre-conditioning value. The arm exercise or the ischaemia alone produced no significant changes in the reflex. Furthermore, neither of these last two conditions was reported to be painful, whereas the ischaemic exercise produced pain in all but one participant. It is concluded that activation of remote nociceptive, but not non-nociceptive, deep somatic nerves can modulate jaw reflexes in man.

Intrathecal prostaglandin E 1 produces a long-lasting allodynic state

The existence of prostaglandin (PG) receptors in the spinal cord has been demonstrated, but their role in sensory processing is not yet well defined. PGE 1 is widely used clinically as a vasodilator. The present study was designed to investigate the effects of intrathecally administered PGE 1 on the transmission of different types of sensory information, including that associated with noxious somatic, noxious visceral, and non-noxious somatic stimulation. The tail-flick (TF) test was employed to measure responses to noxious somatic stimuli, and the colorectal distension test was used to examine responses to noxious visceral stimuli. Withdrawal response to mechanical pressure produced by Semmes-Weinstein mono-filaments (SWMs) was measured as an assessment of sensitivity to non-noxious mechanical somatic stimulation. TF latencies and colorectal distension thresholds decreased for a short time (10–20 min) following the intrathecal (i.t.) administration of both 100 ng or 500 ng of PGE 1. In sharp contrast to these short duration effects, there was a long-lasting increase in agitation scores (allodynia) produced by 3 different intensities of SWMs (0.217, 0.745 and 2.35 g) after administration of PGE 1. The changes in agitation scores to SWMs were dependent on the dose of PGE 1 and the intensity of stimulation. This increase of agitation score was seen when PGE 1 was administered through the i.t. catheter or by direct i.t. puncture and the increase lasted for at least 2 days after drug administration. Intrathecal administration of saline, however, did not produce any changes in TF latencies, colorectal distension thresholds, or agitation scores produced by SWMs. No significant histological difference was seen between spinal cords exposed to 500 ng PGE 1 and saline 48 h after drug administration. These results demonstrate that PGE 1 may trigger a hypersensitive (allodynic and/or hyperalgesic) state in sensory processing pathways at the spinal level. They also indicate that long-lasting changes in processing of non-noxious, but not noxious, information produced by PGE 1 continues after the disappearance of the direct action of PGE 1.