Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Infusions, Spinal”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed1986

The role of spinal cord cyclic AMP in the acoustic startle response in rats.

Drugs thought to increase intracellular levels of cAMP were infused intrathecally into the subarachnoid space of the lumbar spinal cord, and the effects on the acoustic startle response in rats were measured. Intrathecal infusions of the cAMP analogs dibutyryl cAMP or 8-bromo cAMP (12.5-100 micrograms) produced marked, dose-dependent increases in startle amplitude compared to the infusion of artificial cerebrospinal fluid (CSF). Local infusions of dibutyryl cAMP at more rostral levels of the spinal cord or brain failed to mimic the excitatory effect seen following lumbar intrathecal infusion. No excitation of startle was seen following intrathecal infusion of cAMP itself, ATP, 5'-AMP, or dibutyryl cGMP. A weak excitation of startle was seen following intrathecal, but not intraventricular, infusion of the water-soluble adenylate cyclase activator forskolin 7-deacetyl-7-O-hemisuccinic acid (forskolin-DHA; 5.0-100 micrograms, in artificial CSF), whereas forskolin itself [0.01-200 micrograms, in dimethyl sulfoxide (DMSO)] was without consistent effect. Finally, intrathecal infusion of the selective phosphodiesterase inhibitor Rolipram (12.5-200 micrograms) produced a marked excitation of startle similar in magnitude to the effects produced by cAMP analogs. The excitatory effects of intrathecally infused dibutyryl cAMP, 8-bromo cAMP, forskolin-DHA, or Rolipram support a functional link between spinal cord cAMP and the acoustic startle reflex. Possible sites of cAMP action on startle are discussed.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Evaluation of the usefulness of intrathecal bupivacaine infusion for analgesia after hip and knee arthroplasty.

Spinal anaesthesia in 47 ASA I-III patients was induced with 0.5% bupivacaine 2 ml via a 28-gauge spinal catheter (L3-4 interspace) and 0.5-ml increments were given if needed before or during hip or knee arthroplasty. Intrathecal 24-h infusions consisted of 0.5% bupivacaine 0.4 ml h-1 (2 mg h-1) (n = 12), 0.5% bupivacaine 0.2 ml h-1 (1 mg h-1) (n = 12) or saline (n = 11) (12 exclusions). Patients received oxycodone 0.1-0.14 mg kg-1 i.m. for rescue analgesia. Infusion of bupivacaine 2 mg h-1 provided significantly better postoperative analgesia (19 oxycodone doses per group in 24 h) compared with bupivacaine 1 mg h-1 (36 doses of oxycodone per group) and saline (52 doses per group) (P < 0.05). Five patients in the bupivacaine 2-mg h-1 group and none in the other groups had measurable sensory block 24 h after the infusion was started. Three patients in the bupivacaine 2-mg h-1 group, two with concomitant arterial hypotension, and one patient in the bupivacaine 1-mg h-1 group experienced an increase in block on the ward. The incidence of nausea and vomiting was similar in all groups. Although an effective analgesic, intrathecal infusion of bupivacaine 2 mg h-1 cannot be recommended for routine pain relief because of the risk of increasing spinal block. Technical problems (19%) also reduced the overall efficacy of the continuous intrathecal analgesic regimen.

Analgesia↗
PubMed1987

Effect of neuronal uptake blockade on the amplifying effect of serotonin on sympathetic vasoconstriction in rat autoperfused hindlimb.

The effects of serotonin on resting perfusion pressure and on vasoconstrictor responses to electrical stimulation of the lumbar sympathetic outflow were investigated in the autoperfused hindlimb of the pithed rat. beta-Adrenoceptors, muscarinic cholinoceptors, and angiotensin converting enzyme were blocked. Infusion of serotonin (100 ng/min i.a. for 10 min) produced variable increases in hindlimb perfusion pressure of up to 100 mm Hg. During infusion of serotonin, responses to spinal stimulation at 3 Hz for 20 s were decreased, whereas responses at 10 Hz for 10 s were unaffected. Within 5 min of termination of infusion, the direct vasoconstrictor effect of serotonin disappeared, whereas responses to stimulation at both 3 and 10 Hz increased significantly to around 160% of control preinfusion values. In the presence of desipramine (0.1 mg/kg, i.v.), responses to stimulation at 3 Hz were increased; during serotonin infusion the responses were unchanged (i.e., the inhibitory effect observed in the absence of desipramine did not occur), whereas after termination of infusion the responses were again significantly increased. It is concluded that in the rat autoperfused hindlimb, serotonin produces both inhibitory and facilitatory, or amplifying, effects on sympathetic vasoconstrictor responses; increasing the stimulation frequency and neuronal uptake blockade appear to favor the amplifying effect of serotonin.

Animals↗
PubMed2001

Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial.

BACKGROUND: Epidural analgesia is the most effective labour pain relief but is associated with increased rates of instrumental vaginal delivery and other effects, which might be related to the poor motor function associated with traditional epidural. New techniques that preserve motor function could reduce obstetric intervention. We did a randomised controlled trial to compare low-dose combined spinal epidural and low-dose infusion (mobile) techniques with traditional epidural technique. METHODS: Between Feb 1, 1999, and April 30, 2000, we randomly assigned 1054 nulliparous women requesting epidural pain relief to traditional (n=353), low-dose combined spinal epidural (n=351), or low-dose infusion epidural (n=350). Primary outcome was mode of delivery, and secondary outcomes were progress of labour, efficacy of procedure, and effect on neonates. We obtained data during labour and interviewed women postnatally. FINDINGS: The normal vaginal delivery rate was 35.1% in the traditional epidural group, 42.7% in the low-dose combined spinal group (odds ratio 1.38 [95% CI 1.01-1.89]; p=0.04); and 42.9% in the low-dose infusion group (1.39 [1.01-1.90]; p=0.04). These differences were accounted for by a reduction in instrumental vaginal delivery. Overall, 5 min APGAR scores of 7 or less were more frequent with low-dose technique. High-level resuscitation was more frequent in the low-dose infusion group. INTERPRETATION: The use of low-dose epidural techniques for labour analgesia has benefits for delivery outcome. Continued routine use of traditional epidurals might not be justified.

Adult↗
PubMed2006

Sialidase enhances spinal axon outgrowth in vivo.

The adult CNS is an inhibitory environment for axon outgrowth, severely limiting recovery from traumatic injury. This limitation is due, in part, to endogenous axon regeneration inhibitors (ARIs) that accumulate at CNS injury sites. ARIs include myelin-associated glycoprotein, Nogo, oligodendrocyte-myelin glycoprotein, and chondroitin sulfate proteoglycans (CSPGs). Some ARIs bind to specific receptors on the axon growth cone to halt outgrowth. Reversing or blocking the actions of ARIs may promote recovery after CNS injury. We report that treatment with sialidase, an enzyme that cleaves one class of axonal receptors for myelin-associated glycoprotein, enhances spinal axon outgrowth into implanted peripheral nerve grafts in a rat model of brachial plexus avulsion, a traumatic injury in which nerve roots are torn from the spinal cord. Repair using peripheral nerve grafts is a promising restorative surgical treatment in humans, although functional improvement remains limited. To model brachial plexus avulsion in the rat, C8 nerve roots were cut flush to the spinal cord and a peroneal nerve graft was inserted into the lateral spinal cord at the lesion site. Infusion of Clostridium perfringens sialidase to the injury site markedly increased the number of spinal axons that grew into the graft (2.6-fold). Chondroitinase ABC, an enzyme that cleaves a different ARI (CSPGs), also enhanced axon outgrowth in this model. In contrast, phosphatidylinositol-specific phospholipase C, which cleaves oligodendrocyte-myelin glycoprotein and Nogo receptors, was without benefit. Molecular therapies targeting sialoglycoconjugates and CSPGs may aid functional recovery after brachial plexus avulsion or other nervous system injuries and diseases.

Animals↗
PubMed2002

Intracellular QX-314 causes depression of membrane potential oscillations in lamprey spinal neurons during fictive locomotion.

Spinal neurons undergo large cyclic membrane potential oscillations during fictive locomotion in lamprey. It was investigated whether these oscillations were due only to synaptically driven excitatory and inhibitory potentials or if voltage-dependent inward conductances also contribute to the depolarizing phase by using N-(2,6-dimethylphenyl carbamoylmethyl)triethylammonium bromide (QX-314) administered intracellularly during fictive locomotion. QX-314 intracellularly blocks inactivating and persistent Na+ channels, and in some neurons, effects on certain other types of channels have been reported. To detail the effects of QX-314 on Na+ and Ca2+ channels, we used dissociated lamprey neurons recorded under whole cell voltage clamp. At low intracellular concentrations of QX-314 (0.2 mM), inactivating Na+ channels were blocked and no effects were exerted on Ca2+ channels (also at 0.5 mM). At 10 mM QX-314, there was, however a marked reduction of I(Ca). In the isolated spinal cord of the lamprey, fictive locomotion was induced by superfusing the spinal cord with Ringer's solution containing N-methyl-D-aspartate (NMDA), while recording the locomotor activity from the ventral roots. Simultaneously, identified spinal neurons were recorded intracellularly, while infusing QX-314 from the microelectrode. Patch electrodes cannot be used in the intact spinal cord, and therefore "sharp" electrodes were used. The amplitude of the oscillations was consistently reduced by 20-25% in motoneurons (P < 0.05) and unidentified spinal neurons (P < 0.005). The onset of the effect started a few minutes after impalement and reached a stable level within 30 min. These effects thus show that QX-314 causes a reduction in the amplitude of membrane potential oscillations during fictive locomotion. We also investigated whether QX-314 could affect glutamate currents by applying short pulses of glutamate from an extracellular pipette. No changes were observed. We also found no evidence for a persistent Na+ current in dissociated neurons, but these cells have a much-reduced dendritic tree. The results indicate that there is an inward conductance, which is sensitive to QX-314, during membrane potential oscillations that "boosts" the synaptic drive during fictive locomotion. Taken together, the results suggest that inactivating Na+ channels contribute to this inward conductance although persistent Na+ channels, if present on dendrites, could possibly also contribute to shaping the membrane potential oscillations.

Action Potentials↗
PubMed2004

Treatment of childhood spasticity of cerebral origin with intrathecal baclofen: a series of 52 cases.

Continuous intrathecal baclofen infusion (CIBI) for spasticity of spinal and cerebral origin has been practised for over two decades. More recently, it has been used for severe spasticity of cerebral origin in children. Intrathecal baclofen (ITB) appears most beneficial in severe spastic tetraparetics or tetraplegics, but the evaluation of the outcome of ITB and the benefit of the treatment are largely subjective. The evidence base for this treatment has been questioned, in particular for ambulant children, mainly because of the lack of objective outcome measures. Fifty-two spastic tetraparetic children have been treated by this method in Nottingham, from 1998 to 2003. This represents a large homogeneous series of CIBI in children with severe spasticity of cerebral origin. We carried out a prospective audit of our experience, morbidity and observations during that period. We identified that the lack of a suitable scoring system for the evaluation of effectiveness and benefit is a drawback. As a result of these observations a multicentre randomized controlled trial on ITB in tetraplegia-paresis and ambulant children is advocated.

Adolescent↗
PubMed2000

Fenoldopam for controlled hypotension during spinal fusion in children and adolescents.

Fenoldopam is a dopamine1 agonist whose pharmacological effects include vasodilation of the vascular beds of the kidney, mesentery, skeletal muscle, and coronary systems, resulting in a decrease in systemic vascular resistance and mean arterial pressure. The current retrospective review outlines the use of fenoldopam for controlled hypotension during anterior or posterior spinal fusion in 10 children and adolescents, aged 8-14 years and weighing 22-61 kg. Fenoldopam was infused at a starting dose of 0.3-0.5 microg.kg-1. min-1 and increased incrementally to achieve a mean arterial pressure (MAP) of 50-65 mmHg. The desired MAP was achieved in 4-11 min (7+/-2.5 min). The fenoldopam infusion was administered for 135-225 min (160+/-25 min) in doses ranging from 0.2 to 2.5 microg. kg-1.min-1. The mean fenoldopam infusion rate for the 10 cases varied from 0.5 to 1.4 microg.kg-1.min-1 (1.0+/-0.3 microg.kg-1. min-1). No excessive hypotension or clinically significant adverse effects were noted. Statistically significant, but clinically insignificant, increases in heart rate and decreases in PaO2 were noted during the fenoldopam infusion. The baseline heart rate increased from 87+/-13 b.min-1 to a maximum of 114+/-16 b.min-1 (P < 0.0001) during the fenoldopam infusion. In the six patients undergoing posterior spinal fusion, the baseline PaO2 decreased from 232+/-7 mmHg to a low of 199+/-11 mmHg (P=0.0004) during the fenoldopam infusion. Fenoldopam can be used to provide controlled hypotension during spinal surgery in children and adolescents. Future studies, with direct comparison to other commonly used agents, are needed to better define its advantages and disadvantages as well as its effects on estimated blood loss.

Adolescent↗
PubMed1993

The distribution of medication along the spinal canal after chronic intrathecal administration.

Chronic intrathecal drug infusion for the treatment of neurological diseases, such as spasticity and chronic pain, has become an accepted method of therapy in recent years. Concurrent pharmacokinetic studies have shown that the cisternal cerebrospinal fluid (CSF) drug level is considerably lower than the lumbar CSF level during continuous infusion into the lumbar subarachnoid space. One factor that makes analysis of this decline in drug level difficult to quantify is that it is only feasible to sample CSF at the two extremes of the spinal subarachnoid space. Using a radionuclide technique, we have examined the distribution along the spinal canal of a hydrophilic compound, indium-111 diethylenetriamine pentaacetic acid, that was delivered over 72 hours into the lumbar subarachnoid space in five patients with implanted drug pumps. Over a 20-cm distance of the thoracic cord, radionuclide counts decreased gradually so that the indium-111 diethylenetriamine pentaacetic acid concentration surrounding the cord at the T2 vertebral level was 43% of that at the T12 level in four patients. Therefore, it appears that even with a hydrophilic compound, which minimizes spinal cord capillary losses, there is still a considerable reduction of CSF drug concentration along the spinal canal. The clinical implication of this gradual decline in drug level is that for intrathecal infusion of relatively hydrophilic compounds there may not be any advantage in placing the catheter tip at more rostral locations, such as at the midthoracic or cervical cord.

Analgesia, Epidural↗
PubMed1999

Long-term effects of methylprednisolone following transection of adult rat spinal cord.

Clinically, high-dose treatment with the glucocorticosteroid, methylprednisolone (MP), within 8 h after spinal cord injury, has been shown to improve neurological recovery. The current standard of care is to administer MP as a bolus of 30 mg/kg followed by a 23-h infusion of 5.4 mg/kg/h to spinal cord injured patients. To better understand the role of MP in neuroprotection, we have studied how MP administration affects macrophage accumulation, tissue loss, and axonal dieback at 1, 2, 4 and 8 weeks after a complete transection of the eighth thoracic spinal cord in the adult rat. A 30 mg/kg dose of MP was administered intravenously at 5 min, and 2 and 4 h after injury. The number of ED1 (antibody against microglia/macrophages) -positive cells was quantified in a 500-micrometer-wide strip of tissue directly adjacent and parallel to the transection. At all time points, MP treatment led to a significant decrease in the number of ED1-positive cells in both rostral and caudal stumps. Over the 2-month post-transection period, the average MP-induced reduction in the number of ED1-positive cells was 82% in the rostral cord stump and 66% in the caudal stump. Using a computerized image analysis system, it was observed that MP treatment resulted in a significant reduction in tissue loss in both cord stumps at 2, 4 and 8 week post-injury. Over the 2-month post-lesion period, the average MP-induced reduction in tissue loss in the caudal cord stump was higher than that in the rostral stump; 48 versus 37%, respectively. Immunostaining for neurofilaments and growth-associated protein-43 (GAP-43) revealed the presence of numerous axons near and in the lesion site. Anterograde neuronal tracing with biotinylated dextran amine showed that, in MP-treated animals, dieback of vestibulospinal fibres, but not of corticospinal fibres, was significantly diminished at all time points studied. In addition, with MP administration, 1 and 2 weeks after injury, an increase in the number of vestibulospinal fibres was found at 1 and 2 mm from the transection, suggesting transient regenerative sprouting of these fibres. The results demonstrate that treatment with MP shortly after spinal cord transection in the adult rat led to a long-term reduction of ED1-positive cells and spinal tissue loss, reduced dieback of vestibulospinal fibres, and a transient sprouting of vestibulospinal fibres near the lesion at 1 and 2 weeks post-lesion. The possible relationships between the inflammatory changes, spinal tissue sparing, and axonal survival and sprouting are complex and need to be further explored.

Animals↗
PubMed1998

Regeneration of brainstem-spinal axons after lesion and immunological disruption of myelin in adult rat.

We previously observed that the transient developmental suppression of myelination or disruption of mature myelin, by local intraspinal infusion of serum complement proteins along with a complement-fixing, myelin-specific antibody (e.g., anti-Galactocerebroside), facilitated avian brainstem-spinal axonal regeneration after spinal transection. We now report the effects of similar immunological protocols on axonal regeneration in the injured adult rat spinal cord. After a lateral hemisection injury of the T10 spinal cord, infusion of the above reagents, over 14 days at T11, facilitated the regeneration of some brainstem-spinal axons. The hemisection lesion enabled comparisons between the retrograde labeling within an injured brainstem-spinal nucleus and the uninjured contralateral homologue. The brainstem-spinal nucleus examined in detail was the red nucleus (RN), chosen for its relatively compact descending pathway within the dorsolateral cord. Comparing the number of labeled neurons within each RN, of an experimentally myelin suppressed animal, indicated that approximately 32% of injured rubrospinal projections had regenerated into the caudal lumbar cord. In contrast, control-treated animals (e.g., PBS vehicle alone, GalC antibody alone, or serum complement alone) showed little or no axonal regeneration. We also examined the ultrastructural appearance of the treated cords. We noted demyelination over 1-2 segments surrounding the infusion site (T11) and a further two segments of myelin disruption (delamination) on either side of the demyelinated zone. The demyelination is an active process (< 3 days) with microglia and/or macrophages engulfing myelin. Thus, the facilitation of axonal regeneration through the transient suppression of CNS myelin may be fundamental to all higher vertebrates.

Animals↗
PubMedDate not supplied

Toxicity of chronic spinal analgesia in a canine model: neuropathologic observations with dezocine lactate.

The chronic spinal toxicity of dezocine lactate was investigated in mongrel dogs. Dogs received chronic intrathecal infusion from implanted infusion pumps for 28-136 days. Infusion of saline via intrathecal catheters produced leptomeningeal fibrosis, sometimes with spinal cord compression. Dezocine lactate infusion, in addition to similar leptomeningeal changes, was also associated with severe parenchymal lesions in all cases. The exact cause of this toxicity cannot be specifically assigned; potential contributing factors include catheter-induced reaction, pH of the drug, lactate concentration, osmolality and the pharmacologic agent itself. Leptomeningeal reaction in control dogs limits the value of chronic intrathecal dog models for assessment of spinal drug toxicity.

Analgesics, Opioid↗
PubMed2003

The site of action of epidural fentanyl infusions in the presence of local anesthetics: a minimum local analgesic concentration infusion study in nulliparous labor.

UNLABELLED: We have previously demonstrated that continuous epidural infusions of fentanyl without local anesthetics elicit analgesia by a systemic mechanism. In this study, we examined the hypothesis that, in the presence of epidural bupivacaine, continuous infusions of epidural fentanyl elicit analgesia by a spinal mechanism. Forty-eight nulliparous women in active labor participated in this prospective, randomized, double-blinded study. Women received lumbar epidural analgesia with 20-30 mL bupivacaine 0.125% until pain free. Subjects were then randomized to either IV or epidural (EPI) fentanyl infusion groups. Each infusion delivered fentanyl 30 microg/h. All women received an epidural infusion of bupivacaine at a rate of 20 mL/h, the concentration of which was determined by the response of the previous woman in the same group to the analgesic regimen used. Unlike previous studies that assessed the minimum local analgesic concentration (MLAC) for bolus administration at the initiation of analgesia, this study assessed MLAC(infusion) for the maintenance of analgesia throughout the first stage of labor. MLAC(infusion) was determined using the up-down sequential analysis described by Dixon and Massey. The MLAC(infusion) of epidural bupivacaine was 0.063% (95% confidence interval, 0.058-0.068) and 0.019% (95% confidence interval, 0.000-0.038) in the IV and EPI groups respectively. A continuous infusion of fentanyl was more than three times as potent when administered by the epidural than by the IV route. This marked increase in potency for the epidural route is highly suggestive for a predominantly spinal mechanism of action for infused epidural fentanyl under the conditions of this study. IMPLICATIONS: This study determined the median effective concentration for epidural infusions of bupivacaine during labor analgesia. Coadministered epidural fentanyl infusions were more than three times more potent than IV fentanyl infusions, suggesting a predominantly spinal mechanism of opioid action under these study conditions.

Adolescent↗
PubMed2001

The neurophysiology of myofascial pain syndrome.

This article discusses the neurophysiology of myofascial pain syndrome. The local twitch response is a characteristic finding of this condition; it is activated by snapping palpation, pressure, or needle insertion at the trigger point. It is manifested by a burst of activity in the muscle band that contains the activated trigger point. No activity is seen at other muscles bands. Data from experiments with the rabbit indicate that this is a spinal reflex, as it is abolished by transection of the motor nerve innervating the trigger point and infusion of lidocaine. Transection of the spinal cord above the level of the trigger point fails to permanently alter the trigger point response. Needle examination recordings from trigger points show low-voltage spontaneous activity and activity resembling end-plate spikes. This activity is reduced with infusion of phentolamine and local intramuscular infusions of phenoxybenzamine. There are four hypotheses to explain the findings seen at the trigger point. The first is that trigger points are found at the muscle spindle. While this theory may explain the effects of alpha-adrenergic antagonists at the trigger point, it does not fully explain the electromyographic (EMG) findings recorded at the trigger point. The second theory is that trigger points represent hyperactive end-plate regions, as the EMG activity recorded at trigger points resembles that described at the end-plate region. Other theories that either deny the existence of myofascial pain syndrome or believe it represents a focal dystonia are also discussed.

Animals↗
PubMed1997

A new model of spinal cord edema.

Edema of the spinal cord has not been well understood. Brain edema produced by Marmarou's infusion method is essentially similar to vasogenic edema. This infusion method for producing edema was applied to a cat spinal cord. After laminectomy, a 30-gauge needle was inserted into the intumescentia cervicalis. A total amount of 10 microliters of 2% Evans' blue or autoserum were infused using an infusion pump at a rate of 5 microliters/hr. Macroscopally, Evans' blue was observed in the vicinity of infused site at the same level of the needle insertion and was seen spreading mainly longitudinally in the lateral column for a certain distance. The extracellular space was markedly distended in the in fused white mater and filled with electron-dense materials which were thought to be proteins in the electron microscopic study. The fine structural features were similar to the findings which were seen in Marmarou's infusion type of brain edema. Using this model, it seems to be feasible to produce reproducible spinal cord edema at any location in order to investigate not only the morphological aspect but also physiological aspect of the edema.

Animals↗
PubMed1989

Cardiovascular responses to intrathecal administration of strychnine in the rat.

Experiments were done to determine the influence of spinal glycinergic mechanisms in regulating sympathetic output to the heart and vessels in the anaesthetized male Sprague-Dawley rat. Intrathecal administration of 65 (n = 6) and 130 (n = 8) nmol of strychnine, but not of a lower dose (32.5 nmol, n = 8), to the second thoracic segment increased heart rate within one minute (P less than 0.01). Similar administration of artificial cerebrospinal fluid (n = 16) had no effect. The increase in heart rate in response to strychnine peaked at 5-7 min (+35.1 +/- 5.8 bpm with 130 nmol), and slowly returned toward baseline values over the next 25 min. Arterial pressure was unaffected by this treatment. These effects were not mimicked by administration of strychnine (n = 6) at the third lumbar spinal level or by intravenous infusion of strychnine (n = 4) and were abolished by systemic injection of hexamethonium (n = 6). The results suggest that there is a tonic glycine-mediated inhibition of sympathetic output at the spinal level.

Adrenergic Fibers↗
PubMed1987

Monoamine and opioid interactions in spinal analgesia and tolerance.

Noradrenergic and serotonergic neurons, originating in the brainstem and terminating in the dorsal horn, modulate the spinal processing of nociception. The inhibitory effects of norepinephrine (NE) and serotonin (5-HT) on elements of nociceptive transmission may be direct, or secondary to the release of neuromodulators such as opioid peptides. Two major criteria have been used in pharmacological studies of spinal opioid and monoamine interactions: the ability of opioid antagonists to attenuate the antinociceptive effects evoked by stimulating the release of endogenous NE and 5-HT in the lumbar spinal cord, or by the intrathecal injection of exogenous NE and 5-HT; and the development of cross tolerance between opioids and each of NE and 5-HT. Evidence regarding the spinal interaction between opioids and monoamines in mediating behavioural analgesia is reviewed. Recent results from this laboratory indicate that IT (-)naloxone but not (+)naloxone produces dose-dependent antagonism of IT NE-induced antinociception in the rat. This effect was not due to hyperalgesia. In rats made tolerant to spinal morphine using continuous IT infusion, the antinociceptive effect of continuous IT NE was significantly attenuated. However, no cross tolerance was observed between morphine and 5-HT. Observations from a variety of studies support the hypothesis of a spinal opioid link which contributes, in part, to NE-induced antinociception. However, this interaction remains to be conclusively established.

Analgesia↗