Biomedical subjects

Steven L Jinks

Publications and source records attributed to Steven L Jinks.

13 recordsLinked to original sources

PubMed2005

Drastic decrease in isoflurane minimum alveolar concentration and limb movement forces after thoracic spinal cooling and chronic spinal transection in rats.

BACKGROUND: Individuals with spinal cord injury may undergo multiple surgical procedures; however, it is not clear how spinal cord injury affects anesthetic requirements and movement force under anesthesia during both acute and chronic stages of the injury. METHODS: The authors determined the isoflurane minimum alveolar concentration (MAC) necessary to block movement in response to supramaximal noxious stimulation, as well as tail-flick and hind paw withdrawal latencies, before and up to 28 days after thoracic spinal transection. Tail-flick and hind paw withdrawal latencies were measured in the awake state to test for the presence of spinal shock or hyperreflexia. The authors measured limb forces elicited by noxious mechanical stimulation of a paw or the tail at 28 days after transection. Limb force experiments were also conducted in other animals that received a reversible spinal conduction block by cooling the spinal cord at the level of the eighth thoracic vertebra. RESULTS: A large decrease in MAC (to </= 40% of pretransection values) occurred after spinal transection, with partial recovery (to approximately 60% of control) at 14-28 days after transection. Awake tail-flick and hind paw withdrawal latencies were facilitated or unchanged, whereas reflex latencies under isoflurane were depressed or absent. However, at 80-90% of MAC, noxious stimulation of the hind paw elicited ipsilateral limb withdrawals in all animals. Hind limb forces were reduced (by >/= 90%) in both chronic and acute cold-block spinal animals. CONCLUSIONS: The immobilizing potency of isoflurane increases substantially after spinal transection, despite the absence of a baseline motor depression, or "spinal shock." Therefore, isoflurane MAC is determined by a spinal depressant action, possibly counteracted by a supraspinal facilitatory action. The partial recovery in MAC at later time points suggests that neuronal plasticity after spinal cord injury influences anesthetic requirements.

Anesthetics, Inhalation↗

PubMed2005

Isoflurane disrupts central pattern generator activity and coordination in the lamprey isolated spinal cord.

BACKGROUND: Although volatile anesthetics such as isoflurane can depress sensory and motor neurons in the spinal cord, movement occurring during anesthesia can be coordinated, involving multiple limbs as well as the head and trunk. However, it is unclear whether volatile anesthetics depress locomotor interneurons comprising central pattern generators or disrupt intersegmental central pattern generator coordination. METHODS: Lamprey spinal cords were excised during anesthesia and placed in a bath containing artificial cerebrospinal fluid and D-glutamate to induce fictive swimming. The rostral, middle, and caudal regions were bath-separated using acrylic partitions and petroleum jelly, and in each compartment, the authors recorded ventral root activity. The authors selectively delivered isoflurane (0.5, 1, and 1.5%) only to the middle segments of the spinal cord. Spectral analyses were then used to assess isoflurane effects on central pattern generator activity and coordination. RESULTS: Isoflurane dose-dependently reduced fictive locomotor activity in all three compartments, with 1.5% isoflurane nearly eliminating activity in the middle compartment and reducing spectral amplitudes in the anesthetic-free rostral and caudal compartments to 23% and 31% of baseline, respectively. Isoflurane decreased burst frequency in the caudal compartment only, to 53% of baseline. Coordination of central pattern generator activity between the rostral and caudal compartments was also dose-dependently decreased, to 42% of control at 1.5% isoflurane. CONCLUSION: Isoflurane disrupts motor output by reducing interneuronal central pattern generator activity in the spinal cord. The effects of isoflurane on motor output outside the site of isoflurane application were presumably independent of effects on sensory or motor neurons.

Anesthetics, Inhalation↗

PubMed2004

Preserved reticular neuronal activity during selective delivery of supra-clinical isoflurane concentrations to brain in goats and its association with spontaneous movement.

We have previously observed spontaneous movement when supra-clinical concentrations of isoflurane were selectively delivered to the in situ goat brain. We presently examined whether neurons in the midbrain reticular formation (MRF) remained active during such delivery. Isoflurane (5.1+/-1.6%) was selectively delivered to the goat cranial circulation while the torso isoflurane was decreased to 0.2-0.3%. At the high cranial/low torso isoflurane combination, spontaneous movement occurred that usually consisted of running motions, stiffening and twitching. Seventeen MRF neurons recorded in six goats exhibited high spontaneous firing (33+/-20 Hz) despite the presence of an isoelectric electroencephalogram. We conclude that some MRF neurons are resistant to the depressant effect of isoflurane, and may contribute to the observed spontaneous movement.

Action Potentials↗

PubMed2004

Isoflurane differentially modulates medullary on and off neurons while suppressing hind-limb motor withdrawals.

BACKGROUND: Isoflurane acts primarily in the spinal cord to block movement; however, it is unclear how supraspinal sites might contribute to anesthetic effects on quantified parameters of movement such as force. METHODS: The authors investigated the effects of isoflurane on spontaneous and noxious heat-evoked activity of nociceptive reflex-modulating ON and OFF cells in the rostral ventromedial medulla of rats. Single ON or OFF neurons were recorded simultaneously with hind-limb withdrawal force elicited by graded noxious thermal hind paw stimulation. Isoflurane concentrations were administered in reference to each animal's minimum alveolar concentration (MAC) of isoflurane. RESULTS: From 0.65 to 1.15 MAC, isoflurane dose-dependently reduced spontaneous activity of ON cells by 70% (P < 0.001). OFF-cell spontaneous activity was dose-dependently increased 138% (P < 0.001). ON-cell heat-evoked activity was depressed 95% by isoflurane from 0.65 to 1.15 MAC (P < 0.001). Isoflurane-induced changes in ON- and OFF-cell activity paralleled similar reductions in withdrawal force, with the largest change in both neuronal activity and withdrawal force occurring between 0.85 and 1.15 MAC. For the lowest stimulus temperature, excitatory responses of ON cells and inhibitory responses of OFF cells were significantly greater for trials in which withdrawals occurred than for trials in which no withdrawal occurred, suggesting that responses in both classes of neurons were related to movement rather than the stimulus alone. CONCLUSIONS: The results show that isoflurane modulation of ON- and OFF-cell activity corresponds to anesthetic-induced reductions in hind-limb withdrawal force, and therefore, the effects of isoflurane on these classes of neurons in rostral ventromedial medulla might contribute to motor depression.

Animals↗

PubMed2004

Spectral analysis of movement patterns during anesthesia.

UNLABELLED: It remains unclear how anesthetics produce immobility, an end-point used in determining anesthetic potency. Understanding how movement (in response to noxious stimulation) is ablated by anesthetics could be aided by using spectral analysis of the high and low frequency components of complex movement patterns. We therefore applied a spectral analysis to previously published movement data from rats anesthetized with isoflurane and halothane at 0.6, 0.9, and 1.1 minimum alveolar concentration (MAC). We recorded isometric forces of hindlimb movement elicited by noxious mechanical stimulation of the hindpaw. The movement patterns were subjected to spectral analysis to determine force amplitude for each frequency component. When halothane was increased from 0.6 to 0.9 MAC, force amplitude decreased only for the lowest-frequency (<1 Hz) components, in part related to the generally lower high-frequency forces at 0.6 MAC. Between 0.6 and 0.9 MAC isoflurane amplitude was reduced for most frequencies in the 0-10 Hz range. For both halothane and isoflurane at 1.1 MAC, as expected, force amplitude substantially decreased at all frequencies. We conclude that spectral analysis is useful to describe and quantify the effects of anesthetics on complex movement patterns resulting from noxious stimuli applied during anesthesia. IMPLICATIONS: Complex movement can occur when a noxious stimulus is applied to an anesthetized animal. The frequency components of these movement patterns can be described and quantified by spectral analysis, thus providing a useful tool to investigate the immobilizing properties of anesthetics.

Algorithms↗

PubMed2004

Isoflurane depresses windup of C fiber-evoked limb withdrawal with variable effects on nociceptive lumbar spinal neurons in rats.

Windup is a progressive increase in responses of nociceptive spinal cord neurons to repeated electrical C fiber stimulation. We hypothesized that isoflurane would depress windup at approximately the minimum alveolar anesthetic concentration (MAC) required to suppress purposeful movement in response to noxious stimulation. We recorded windup responses in single lumbar spinal neurons (n = 17) to a series of 15 repetitive electrical stimuli delivered at 1 Hz to the hindpaw at C fiber strength; hindpaw withdrawal force was simultaneously recorded. The total number of action potentials per 15 stimuli (mean +/- sem as a percentage of each neuron's maximal response) was 83% +/- 5%, 84% +/- 5%, 67% +/- 7%, and 57% +/- 8% at 0.7, 0.9, 1.1, and 1.4 MAC, respectively. The 0.9 and 1.1 MAC values differed significantly from each other, whereas the 0.7 and 0.9 MAC values differed from the 1.4 MAC value (P < 0.05). The reduced firing was attributed to a depression of the initial C fiber-evoked responses in most units, and a reduction in windup slope over the initial 5 stimuli in 6 units. Muscle force was 67%, 11%, and 4% of the 0.7 MAC value at 0.9, 1.1, and 1.4 MAC, respectively. Isoflurane depressed excitability and variably affected windup of lumbar spinal cord neurons, while uniformly depressing windup of limb withdrawals in a concentration-dependent manner.

Action Potentials↗

PubMed2003

Deletion of the preprotachykinin A gene in mice does not reduce scratching behavior elicited by intradermal serotonin.

Itch is thought to be signaled by a sub-population of pruritogen-selective C-fiber primary afferents. To assess a possible role of the neuropeptide, substance P (SP), in the central neurotransmission of itch, we investigated itch-related scratching behavior elicited by intradermal injection of serotonin (5-HT; 0.03-0.3%) in normal mice (wildtype, WT) and knockout mice (KO) with deletion of the preprotachykinin A gene. Both KO and WT groups showed dose-related increases in the number of 5-HT-evoked scratching bouts over the 44 min observation period. There were no significant differences in the numbers or durations of scratching bouts between WT and KO groups, although KO mice exhibited numerically more spontaneous and 5-HT-evoked scratching. It is concluded that either SP is not involved in the central neurotransmission of itch-related scratching behavior in this strain of mouse, or that compensatory developmental changes in the KO mice allow itch-related signaling.

Animals↗

PubMed2003

Peri-MAC depression of a nociceptive withdrawal reflex is accompanied by reduced dorsal horn activity with halothane but not isoflurane.

BACKGROUND: Anesthetics act in the spinal cord to suppress movement evoked by a noxious stimulus, although the exact site is unknown. METHODS: This study investigated sensorimotor processing in hind limb withdrawal reflexes, and effects of two general anesthetics, halothane and isoflurane, on simultaneously recorded responses of single dorsal horn neurons and hind limb withdrawal force, elicited by graded noxious thermal hind paw stimulation in rats. Minimum alveolar anesthetic concentration (MAC) needed to block gross movement to a supra-maximal mechanical stimulus was determined for each animal. RESULTS: Between 0.9 and 1.1 MAC, halothane and isoflurane greatly reduced or abolished withdrawal force (79 and 89% reduction, respectively). Halothane (0.75-1.4 MAC) depressed heat-evoked neuronal responses in a concentration-related manner (41% reduction between 0.9 and 1.1 MAC averaged across all stimulus temperatures, P < 0.05) and decreased stimulus-response function slopes, with corresponding reductions in withdrawal force. In contrast, isoflurane did not reduce neuronal responses in the 0.75-1.4 MAC range and slightly facilitated responses (by 16%) when concentration increased from 0.9 to 1.1 MAC, despite a concurrent withdrawal force reduction. Anesthetic depression of heat-evoked withdrawal force correlated well with MAC determination using a supra-maximal mechanical stimulus. At sub-MAC anesthetic concentrations, some units exhibited firing rate changes that preceded and paralleled moment-to-moment changes in force during a given withdrawal. CONCLUSIONS: Halothane reduces noxious-evoked movement at least partly via depression of dorsal horn neurons, whereas isoflurane suppresses movement by an action at more ventral sites in the spinal cord.

Animals↗

PubMed2003

Isoflurane depresses diffuse noxious inhibitory controls in rats between 0.8 and 1.2 minimum alveolar anesthetic concentration.

UNLABELLED: Diffuse noxious inhibitory control (DNIC) occurs when the response to a noxious stimulus is inhibited by a second, spatially remote noxious stimulus. The minimum alveolar anesthetic concentration (MAC) to suppress movement is not altered by a second remote noxious stimulus. We hypothesized that DNIC would be depressed in the peri-MAC range. Rats were anesthetized with isoflurane, and MAC was measured. We recorded dorsal horn neuronal responses to noxious thermal stimulation of the hindpaw, with or without concomitant supramaximal noxious mechanical stimulation of the tail or contralateral hindpaw. At 0.8 MAC, the tail clamp decreased neuronal responses 70% compared with control heat-evoked responses (from 1032 +/- 178 impulses per minute to 301 +/- 135 impulses per minute; P < 0.05). The tail clamp had no significant effect on neuronal responses at 1.2 MAC (from 879 +/- 139 impulses per minute to 825 +/- 191 impulses per minute; P > 0.05). Similarly, 1.2 MAC isoflurane significantly depressed DNIC elicited by hindpaw clamping. In another group, the cervical spinal cord was reversibly blocked by cooling to determine whether the inhibition was mediated supraspinally. With spinal cord cooling, the counterstimulus-evoked inhibition was not observed at 0.8 MAC. These results suggest that DNIC involves supraspinal structures and is present at sub-MAC isoflurane concentrations but is depressed at more than 1 MAC. IMPLICATIONS: Diffuse noxious inhibitory control (DNIC) occurs when a noxious stimulus is perceived as being less painful when a second noxious stimulus is applied elsewhere on the body. DNIC is present in anesthetized animals, although how anesthesia affects it is unknown. We found that isoflurane depressed DNIC in the transition from 0.8 to 1.2 minimum alveolar anesthetic concentration, suggesting that DNIC is depressed in the anesthetic range needed to suppress movement.

Action Potentials↗

PubMed2002

C-fos induction in rat superficial dorsal horn following cutaneous application of noxious chemical or mechanical stimuli.

The method of c-fos immunodetection was used to map the distributions of neurons in the lumbar spinal dorsal horn that were activated following intracutaneous (i.c.) microinjection, or iontophoretic application, of different irritant chemicals to the lateral hindpaw of rats. Microinjections (1 microl) of histamine, serotonin (5-HT), nicotine, capsaicin, or formalin each elicited similar distributions of Fos-like immunoreactivity (FLI) in laminae I-II of the ipsilateral superficial dorsal horn, with little or no FLI in deeper laminae or contralaterally. In laminae I and II, FLI cell counts were significantly higher following i.c. histamine, 5-HT, capsaicin, formalin, and noxious pinch, compared to i.c. saline controls. Capsaicin-evoked FLI was dose-dependent. Multivariate analysis of variance revealed no significant difference in spatial distributions of FLI induced by any of the chemical or pinch stimuli. Iontophoretic application of histamine, 5-HT, or nicotine also elicited similar distributions of FLI in the superficial dorsal horn, and cell counts of FLI were significantly higher compared to controls receiving iontophoretic vehicle (methyl cellulose). These results indicate either that individual laminae I-II neurons are activated by each of the irritant chemicals, or that neurons selectively responsive to a given irritant are comingled without any apparent laminar segregation.

Administration, Cutaneous↗

PubMed2002

Isoflurane, but not halothane, depresses c-fos expression in rat spinal cord at concentrations that suppress reflex movement after supramaximal noxious stimulation.

UNLABELLED: We investigated the effects of isoflurane and halothane on the induction of fos-like immunoreactivity (FLI) in the rat lumbosacral spinal cord after supramaximal noxious mechanical stimulation of the hindpaw. Compared with unstimulated controls (0.9% isoflurane), noxious stimulation at 0.9%-1.5% elicited significant (0.9%-1.5% isoflurane) increases in FLI bilaterally. FLI was distributed mainly in the superficial dorsal horn (laminae I-III) and, to a lesser extent, in the deep dorsal horn (laminae IV-VI) and intermediate zone (lamina VII), with three- to fivefold greater labeling ipsilaterally. At 1.8% isoflurane, mean FLI counts in all laminar regions were significantly smaller (1.7 +/- 1.3 per section) compared with the other concentrations (11.4 +/- 9.5, 7.5 +/- 6.8, and 9.7 +/- 6.6 at 0.9%, 1.2%, and 1.5%, respectively) but were not different from unstimulated controls. At sacral levels, we observed a bilateral distribution of FLI primarily in superficial laminae in unstimulated controls that was not significantly different at any isoflurane concentration. FLI counts were not significantly different across groups receiving halothane (0.9%-1.5%). FLI was reduced only at isoflurane concentrations that depressed both gross, purposeful movement and reflex withdrawal, whereas halothane did not cause depression even at concentrations that depressed withdrawal reflexes. Isoflurane and halothane may have differing effects on neuronal function and responses to noxious stimulation. IMPLICATIONS: Isoflurane depressed neuronal activity in the spinal cord as measured with fos-like immunoreactivity (FLI), but this occurred only when reflex withdrawal responses were abolished. Halothane, however, did not depress FLI, even at concentrations sufficient to block reflex withdrawal. These two anesthetics may have differing effects on neuronal function and responses.

Anesthetics, Inhalation↗

PubMed2002

Responses of superficial dorsal horn neurons to intradermal serotonin and other irritants: comparison with scratching behavior.

Scratching behavior is used to assess itch sensation in animals, but few studies have addressed the relative scratch-inducing capacity of different algesic and pruritic chemicals. Furthermore, central neural mechanisms underlying itch are not well understood. We used electrophysiological and behavioral methods to investigate the ability of several irritant chemicals to excite neurons in the superficial dorsal horn, as well as to elicit scratching, in rats. In anesthetized rats, single neurons in the superficial lumbar dorsal horn, identified by their responsiveness to intracutaneous (ic) histamine, were classified as wide dynamic range (WDR) or nociceptive-specific (NS). Serotonin (5-HT) given ic to the paw excited most (88%) WDR and NS neurons over a prolonged time course (often up to 40 min). 5-HT-evoked responses exhibited significant tachyphylaxis. Most neurons also gave shorter-duration responses to ic capsaicin (92%) and mustard oil (71%). In separate behavioral experiments, significant dose-related hind limb scratching directed at the ic injection site in the back of the neck was elicited by 5-HT over a time course similar to that of evoked neuronal firing. A second 5-HT injection made 40 min later at the same site elicited significantly less scratching. Formalin also elicited scratching that was not dose-related and less than that evoked by 5-HT. 5-HT and Formalin also evoked head or whole-body shakes that were significantly correlated with scratching. Neither histamine, capsaicin, nor vehicle controls elicited significant scratching or shaking. In rats, 5-HT appears to be more pruritogenic than histamine as assessed by scratching and shaking behavior, and excites superficial dorsal horn neurons over a behaviorally relevant time course. However, because most neurons additionally responded to pain-producing stimuli, they are not itch-specific. They might nonetheless contribute to neural pathways that distinguish between pain and itch based on some neural mechanism such as frequency coding.

Animals↗

PubMedDate not supplied

A model for differential volatile anesthetic delivery to the upper and lower torso of the rabbit.

INTRODUCTION: We have developed a model that permits differential delivery of volatile anesthetics to the upper and lower torso of the rabbit. METHODS: Rabbits were anesthetized with isoflurane (n = 4) or halothane (n = 3), and blood was drained from a carotid cannula into a membrane oxygenator and reinfused via a renal artery cannula into the lower torso circulation using a roller pump. Bypass of the lower torso circulation was achieved by tightening a ligature around the aorta at the level of the renal arteries. Blood concentrations of anesthetic (assessed by gas chromatography) and cardiovascular responses to noxious stimulation were determined with and without anesthetic delivery to the membrane oxygenator. RESULTS: When the anesthetic was removed from the oxygenator gas flow, the arterial concentration of isoflurane in the lower torso was 28 +/- 15 microg/ml, while it was 133 +/- 28 microg/ml in the upper torso circulation; the corresponding values for the halothane-anesthetized rabbits were 63 +/- 8 and 270 +/- 49 microg/ml. There was a significant correlation (r=.92-.99) between pump flow and lower torso pressure in each individual rabbit. When anesthetic was delivered to both upper and lower torso, noxious electrical stimulation of the tail or hindpaw did not affect lower torso pressures (52 +/- 10 to 54 +/- 12 mmHg). Decreasing the anesthetic concentration in the lower torso resulted in significant increases in lower torso blood pressure during noxious stimulation (82 +/- 19 to 131 +/- 35 mmHg, P < .05). DISCUSSION: The results indicate that volatile anesthetics isoflurane and halothane can be differentially delivered to the upper and lower torso of the rabbit, with an approximate 75-80% reduction in the anesthetic concentration in the lower torso when the anesthetic is eliminated from the gas flow to the oxygenator. This preparation can be used to study the pharmacological properties of volatile anesthetics.

Abdomen↗