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M J Esser

Publications and source records attributed to M J Esser.

At least 19 recordsLinked to original sources
PubMed2001

Chronic administration of amitriptyline and caffeine in a rat model of neuropathic pain: multiple interactions.

This study was designed to determine (1) whether chronic amitriptyline administration was effective in alleviating symptoms of neuropathic pain in a rat model of spinal nerve injury, and (2) whether the effect of amitriptyline involved manipulation of endogenous adenosine, by determining the effect of caffeine, a non-selective adenosine A(1) and A(2) receptor antagonist, on its actions. Nerve injury was produced by unilateral spinal nerve ligation of the fifth and sixth lumbar nerves distal to the dorsal root ganglion, and this resulted in stimulus-evoked thermal hyperalgesia and static tactile mechanical allodynia. Animals received pre- and post-surgical intraperitoneal doses of amitriptyline (10 mg/kg) and caffeine (7.5 mg/kg), alone or in combination, and following surgery, were administered amitriptyline (15-18 mg/kg/day) and caffeine (6-8 mg/kg/day), alone or in combination, in the drinking water. Rats were tested for thermal reaction latencies and static tactile thresholds at 7, 14 and 21 days following surgery. In the paw ipsilateral to the nerve ligation, chronic amitriptyline administration consistently decreased the thermal hyperalgesia produced by spinal nerve ligation over a 3-week period, and this effect was blocked by concomitant caffeine administration at all time intervals. In the contralateral paw, thermal withdrawal latencies were more variable, with the most reproducible finding being a reduction in thermal thresholds in the amitriptyline-caffeine combination group. There was no effect by either drug or the drug combination on the static tactile allodynia produced by spinal nerve ligation in the ipsilateral paw. However, chronic amitriptyline administration induced a tactile hyperaesthesia in the contralateral paw at all time intervals, and this effect was exacerbated by concomitant chronic caffeine administration. The results of this study indicate that chronic administration of amitriptyline is effective in alleviating thermal hyperalgesia, but not static tactile allodynia, in the hindpaw ipsilateral to nerve injury, and the block of this effect by caffeine suggests that this effect is partially achieved through manipulation of endogenous adenosine systems. Additionally, chronic amitriptyline administration induces contralateral hyperaesthetic responses that are augmented by caffeine. Both the symptom-specific effect, and adenosine involvement in amitriptyline action may be important considerations governing its use in neuropathic pain.

Amitriptyline↗
PubMed2001

Antidepressants as analgesics: an overview of central and peripheral mechanisms of action.

Antidepressants, given systemically, are widely used for the treatment of various chronic and neuropathic pain conditions in humans. In animal studies, antidepressants exhibit analgesic properties in nociceptive, inflammatory and neuropathic test systems, with outcomes depending on the specific agent, the particular test, the route of administration and the treatment method used. Although early studies focused on central (i.e., supraspinal, spinal) actions, more recent studies have demonstrated a local peripheral analgesic effect of antidepressants. These peripheral actions raise the possibility that topical formulations of antidepressants may be a useful alternative drug delivery system for analgesia. Antidepressants exhibit a number of pharmacological actions: they block reuptake of noradrenaline and 5-hydroxytryptamine, have direct and indirect actions on opioid receptors, inhibit histamine, cholinergic, 5-hydroxytryptamine and N-methyl-D-aspartate receptors, inhibit ion channel activity, and block adenosine uptake. The involvement of these mechanisms in both central and peripheral analgesia produced by antidepressants is considered. Data illustrating the preclinical peripheral analgesic actions of antidepressants are presented, as are some aspects of the mechanisms by which these actions occur.

Analgesics, Non-Narcotic↗
PubMed2000

Caffeine blockade of the thermal antihyperalgesic effect of acute amitriptyline in a rat model of neuropathic pain.

In the present study, we sought to determine whether administration of caffeine, a non-selective adenosine receptor antagonist, would affect the thermal antihyperalgesic efficacy of acute amitriptyline in a rat model of neuropathic pain. Rats were rendered neuropathic by unilateral tight ligation of the fifth and sixth lumbar spinal nerves, and tested for thermal hyperalgesia using a focused beam of light. Systemic administration of caffeine (1.5-7.5 mg/kg), at the same time as amitriptyline, blocked the thermal antihyperalgesic effect of 10 mg/kg amitriptyline. The greatest degree of block exerted by caffeine was observed with 3.75 mg/kg (100% block), a dose that had no observable intrinsic effect. Spinal administration of amitriptyline (60 microg) exhibited a mild antihyperalgesic effect that was unaffected by pretreatment with intrathecal caffeine (100 microg). Peripheral administration of amitriptyline into the neuropathic paw (under brief anesthesia) produced an antihyperalgesic effect at both 30 and 100 nmol, with a greater effect being observed at 100 nmol. Coadministration of caffeine (1500 nmol) partially antagonized the effects of both doses of amitriptyline. The results of this study suggest that the thermal antihyperalgesic effect of acute amitriptyline in this model may involve enhancement of an endogenous adenosine tone. This involvement is important in light of the widespread consumption of caffeine, which may potentially act to reduce the benefits of amitriptyline in the treatment of neuropathic pain.

Amitriptyline↗
PubMed2000

Conditioning effects of repetitive mild neurotrauma on motor function in an animal model of focal brain injury.

A weight drop model of brain injury was used to determine the effects of repetitive mild brain injury on motor function, heat shock protein and glial fibrillary acidic protein expression in the anesthetized, adult male, Sprague-Dawley rat. Repetitive mild brain injury was produced when animals received a series of three mild injuries spaced three days apart. A separate group of repetitive mild injured animals also received a subsequent severe brain injury between three and five days after the last mild injury. All animals were trained on a beam-walking test prior to surgery. The mild, repetitive mild and repetitive mild plus severe brain injury groups showed no motor deficits in the beam-walking test, whereas the animals with only severe brain injury showed significant motor deficits (increase in number of footslips) in the beam-walking test that recovered within eight days after injury. Both repetitive mild plus severe injury and severe injury only animals had cortical necrotic cavities of similar size in the region of the hindlimb motor cortex. Both the repetitive mild and severe brain-injured animals had marked heat shock protein 27kDa and glial fibrillary acidic protein staining in the cerebral cortex. Fluoro-Jade, heat shock protein 27kDa and 72kDa labeling indicated that there were widespread effects on cortical, subcortical and spinal neurons and glial cells after repetitive mild brain injury. These results suggest that repetitive mild brain injury conditions the brain so that subsequent brain injury at the same site has no effect on motor function. Furthermore, repetitive mild injury-induced activation of processes distant to the primary injury site may have a role in activation of secondary sites involved in recovery of motor function.

Animals↗
PubMed1999

Peripheral antinociceptive action of amitriptyline in the rat formalin test: involvement of adenosine.

The present study determined (1) whether amitriptyline could produce a local antinociceptive action in the formalin test, (2) whether endogenous adenosine was involved in this action, and (3) which other systems might contribute to such an action. Coadministration of amitriptyline 10-100 nmol with 2.5% formalin produced a dose-related reduction in phase 1 (0-12 min) and phase 2 (16-60 min) flinching behaviours, as well as in phase 2 biting/licking time (no phase 1 expression). This action was not seen or only partially expressed at low concentrations of formalin (0.5%, 0.75%). Coadministration of caffeine with amitriptyline partially reversed the antinociceptive action of amitriptyline against both behaviours at 2.5% formalin. At 1.5% formalin, caffeine still produced only a partial reversal of effect; this appeared to be due to a block of adenosine A1 receptors, as it was also seen with the selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine. Using antagonists for a number of other systems, no evidence for an involvement of alpha-adrenergic, histamine, excitatory amino acid or opioid receptors in the action of amitriptyline was observed or inferred. A local anaesthetic action for amitriptyline remains a possibility for the residual action. These results indicate that amitriptyline can produce a local peripheral antinociceptive action which is mediated, in part, by an interaction with endogenous adenosine, most likely an inhibition of the cellular uptake of adenosine with a consequent activation of adenosine A1 receptors on sensory nerve terminals. Local application of amitriptyline by cream or gel might prove to be a useful method of drug delivery in inflammatory pain states.

Adenosine↗
PubMed1999

Peripheral antinociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat.

Amitriptyline, a non-selective noradrenaline (NA) and 5-hydroxytryptamine (5-HT) reuptake inhibitor, has recently been demonstrated to produce a peripheral antinociceptive action in an inflammatory (formalin test) and a neuropathic pain model (spinal nerve ligation). In the present study, we determined whether desipramine, a selective NA reuptake inhibitor, and fluoxetine, a selective 5-HT reuptake inhibitor, could produce peripheral antinociceptive actions in these same tests. Effects on paw volume also were determined. In the 2.5% formalin test, desipramine and fluoxetine 10-300 nmol produced a dose-related reduction in phase 2 (16-60 min) flinching and biting/licking behaviours when coadministered with the formalin. Phase 1 flinch behaviours (0-12 min) were significantly reduced at the highest dose. These actions are peripherally mediated, as they were not seen when desipramine or fluoxetine (100, 300 nmol) were injected into the contralateral hindpaw. The peripheral action of desipramine and fluoxetine was not altered by coadministration of caffeine 1500 nmol. In the spinal nerve ligation model, desipramine 100 nmol, but not fluoxetine 100 nmol, produced a peripheral anti-hyperalgesic action in the hindpaw corresponding to the ligated side when thresholds were determined using a thermal paw stimulator. In paw volume experiments, desipramine, at doses which are maximally effective in behavioural tests, produced only a slight increase in paw volume, but fluoxetine (10-300 nmol) produced a robust and sustained dose-related increase in paw volume. Amitriptyline also produced minimal effects on paw volume. When coinjected with formalin, no agent significantly altered the degree of paw swelling produced by formalin. The increase in paw volume produced by fluoxetine was inhibited by ketanserin (5-HT2 receptor antagonist), mepyramine (histamine H1 receptor antagonist) and phentolamine (alpha-adrenergic receptor antagonist), but not by the other selective 5-HT receptor antagonists tested or caffeine. The pronounced peripheral pain alleviating actions in the absence of marked changes in paw volume produced by desipramine and amitriptyline, but not fluoxetine, in the formalin test and the spinal nerve ligation model suggest that these agents could be developed as cream or gel formulations to recruit a peripheral antinociceptive action in inflammatory and neuropathic pain states. Such a formulation might permit the attainment of higher and more efficacious concentrations in the region of the sensory nerve terminal, with limited systemic side effects.

Adrenergic Uptake Inhibitors↗
PubMed1998

Trigeminal-reticular connections: possible pathways for nociception-induced cardiovascular reflex responses in the rat.

Cardiovascular regulatory neurons of the ventral medulla and pons are thought to have an important role in the mediation of trigeminal nociception-induced reflex cardiovascular responses. However, the neural pathways that link the spinal trigeminal nucleus with ventral medullary and pontine autonomic cell groups are poorly understood. The present study utilized injections of the highly sensitive anterograde tracer substance biotinylated dextran combined with immunocytochemistry for tyrosine hydroxylase, the synthesizing enzyme for catecholamines, to investigate the distribution and morphology of projections from the spinal trigeminal subnucleus caudalis to ventral medullary and pontine catecholaminergic cell groups. Injection of biotylinated dextran into the dorsal subnucleus caudalis produced dense anterograde labeling in dorsal regions of the medullary and pontine reticular formation including the dorsal medullary reticular field, the parvicellular reticular field, and the parvicellular reticular field pars anterior. In the ventral medullary and pontine reticular formation, light anterograde labeling tended to be distributed in close proximity to the distal dendrites of catecholaminergic neurons located in the C1, A1, and A5 regions. Injections of anterograde tracer into the dorsal medullary reticular field produced dense anterograde labeling in the ventral medullary and pontine reticular formation. Numerous terminal-like varicosities were observed in close proximity to catecholaminergic neurons located in the C1, A1, and A5 regions. These data suggest that trigeminal pain-induced reflex cardiovascular responses involve indirect projections that terminate in the dorsal medullary and pontine reticular formation before reaching ventral medullary and pontine catecholaminergic cell groups known to be involved in cardiovascular regulation.

Animals↗
PubMed1997

Prescribing of analgesics in trauma patients.

OBJECTIVE: To evaluate whether initial orders of pain medications by physicians for trauma patients were in accordance with published guidelines. DESIGN: Concurrent, nonrandomized investigation conducted over 4 months. MATERIALS AND METHODS: All adult trauma patients admitted to the intensive care unit within 12 hours of injury who stayed for at least 1 hour were eligible for study admission. Patients with injuries prohibiting accurate pain assessment (e.g., Glasgow Coma Score < 8, spinal cord injury) were excluded. Initial orders for pain medications were compared to published guidelines; correlations between dose and patient demographics were studied. RESULTS: Of the 30 patients enrolled in the study, 83% were prescribed appropriate pain control regimens. The average dose of morphine administered during each of the 8-hour dosing intervals was approximately 12 mg. No relationship was found between patient age, sex, Glasgow Coma Score, and morphine dose; however, there was a positive correlation found between Injury Severity Score and dose. CONCLUSIONS: The majority of patients in this investigation were initially prescribed appropriate doses and intervals for pain management.

Adolescent↗
PubMed1996

Trigeminal-parabrachial connections: possible pathway for nociception-induced cardiovascular reflex responses.

Noxious stimulation of dental nerves elicits marked changes in cardiovascular function. In order to investigate central pathways mediating reflex changes in cardiovascular activity, immunohistochemical localization of cells expressing the immediate-early gene, c-fos, was used to identify central nervous responding to noxious electrical stimulation of mandibular, incisor tooth dentin or chemical (capsaicin) stimulation of tooth pulp in the anesthetized rat. Injections of Fluoro-Gold were made in the lateral parabrachial region to identify efferent projections from the spinal trigeminal nucleus. Electrical and chemical stimulation produced similar patterns of Fos-positive neurons in the spinal trigeminal nucleus: subnuclei caudalis, interpolaris and oralis. Fos-positive neurons were most dense in laminae I and II of the dorsomedial subnucleus caudalis with fewer Fos-positive neurons located in the interpolaris and oralis subnuclei. Sham stimulation of tooth dentin and control vehicle injections into the tooth pulp resulted in either a few weakly stained or no Fos-positive neurons in the spinal trigeminal nucleus. Cell bodies double labeled with Fluro-Gold following injections into the parabrachial region and Fos-protein subsequent to electrical stimulation of incisor tooth were present in all three subnuclei of the spinal trigeminal nucleus. The largest number of Fos-positive neurons with efferent projections to the lateral parabrachial region were located in subnucleus caudalis (32.2 +/- 5.3 S.E.M.) and fewer were located in the interpolaris (0.4 +/- 0.4 S.E.M.) and oralis (19.8 +/- 3.5 S.E.M.) subnuclei. The results demonstrate that nociceptive dental input received by the three subnuclei of the spinal trigeminal nucleus, particularly the subnucleus caudalis, is relayed to the lateral parabrachial nucleus.

Animals↗
PubMed1992

A new method of diagnosing diaphragmatic injury using intraperitoneal technetium: case report.

The diagnosis of diaphragmatic laceration following blunt or penetrating trauma is often difficult to establish. Delay in recognition of this injury can be life threatening, resulting in herniation of abdominal viscera with possible strangulation or respiratory embarrassment. Previous animal studies from our institution have documented that intra-abdominal instillation of technetium sulfur colloid is a sensitive method to diagnose diaphragmatic disruption. We now present a case of diaphragmatic injury where the preoperative diagnosis was accurately made using this method when other imaging studies were inconclusive.

Adult↗
PubMed1992

Updating the management of salvageable splenic injury.

Because of the ready availability of autotransfusers and risk of transfusion-transmitted disease, the authors reexamined the management of splenic trauma. During the past 6 months, 20 adult and pediatric patients were treated for blunt splenic trauma. Nine had "minor" lacerations and were successfully managed nonoperatively. Eleven had ongoing hemorrhage or associated visceral injury necessitating laparotomy. In two, coexistent injuries were life threatening and total splenectomy was performed. The other nine had major splenic trauma that was either an isolated phenomenon or was associated with an injury not jeopardizing survival; eight spleens were salvaged. Mean intra-abdominal blood loss was approximately 1250 mL and, using a "cell saver," an average of approximately 790 mL was reinfused. Six received no other blood transfusion whereas three received 2250 mL homologous blood in addition to 4250 mL via the "cell-saver." With hilar laceration, repair was facilitated by temporarily occluding the splenic pedicle atraumatically, and suturing torn polar branches via the laceration site. In both children and adults with major splenic injury, the authors now recommend early laparotomy with reinfusion of autologous blood. The spleen or a large remnant can usually be salvaged, and homologous blood transfusion with its attendant complication can often be obviated altogether.

Adolescent↗
PubMed1989

Effects of vagal cryo-interruption on colon contractions in monkeys.

The influence of the vagus nerve on normal colon contractions, and the distal extent of this influence along the colon, is unknown. It is generally thought that the vagus nerve has little, if any, influence on normal colon contractions, and if there is any effect, it is limited to the proximal colon. The technique of reversible truncal vagotomy by cooling (vagal cryo-interruption) was used to explore the influence, and extent of any influence, of the vagus nerve on contractions of the colon in unanesthetized monkeys. Each monkey was subjected to vagal cryo-interruption in the fasted and fed states. In both states this caused a significant decrease in contractions in the proximal, middle, and distal portions of the colon, compared with baseline control and recovery periods. These studies indicate that the vagus nerve plays a role in normal contractions of the intra-abdominal colon in both the fasted and the fed states and that it also plays a role in the gastrocolic response.

Animals↗
PubMed1987

[Cardiogenic shock].

Explore the source record for details and available documents.

Angioplasty, Balloon↗
PubMed1987

Effects of adrenergic agents on colonic motility.

Sympathetic hyperactivity has been implicated as an etiologic factor in postoperative ileus. The effects of methoxamine (alpha-agonist) and isoproterenol (beta-agonist) on colon contractions and blood flow were studied in nine monkeys. Phentolamine (alpha-antagonist) and propranolol (beta-antagonist) were used to block the effects of the appropriate agonist. Methoxamine caused a dose-related inhibition of colon contractions and a decrease in inferior mesenteric artery (IMA) blood flow. Isoproterenol caused a dose-related inhibition of colon contractions and an increase in IMA blood flow. The contractile and blood flow effects of methoxamine were blocked by phentolamine and those of isoproterenol by propranolol. Mechanical reduction of IMA blood flow by an amount equivalent to that observed with the highest dose of methoxamine caused no change in contractions in the segment of colon supplied by the IMA. Both alpha- and beta-agonists inhibit colon contractions and have the expected effects on IMA blood flow. The contractile and blood flow responses of the agonists can be blocked by appropriate antagonists. The blood flow changes are not responsible for the contractile changes. These results indicate that sympathetic hyperactivity may play a role in postoperative ileus.

Animals↗
PubMed1983

Reversible truncal vagotomy in conscious dogs.

Prior attempts at in vivo reversible vagal denervation of the gastrointestinal tract have been limited to cervical cooling techniques that also denervate both sympathetic and vagal pulmonary and cardiac branches. Denervation of vagal efferent fibers at this level has produced results that are inconsistent with those obtained after surgical truncal vagotomy. We have, therefore, developed a technique to provide reversible vagal denervation below the pulmonary and cardiac branches for the study of gastric motility. Five dogs, previously equipped with gastric strain gages and electrodes, underwent implantation of a tubular cooling jacket around a distal thoracic vagal trunk with contralateral vagotomy (4 dogs), or around both vagal trunks (1 dog). The jacket was made of stainless steel tubing in a "J" design. Its inside channel was lined with a sterling silver sheet, and a thermistor was attached to record temperature change. Silicone tubing coursed externally to a pump and flask to which 95% ethanol at -70 degrees C was circulated at variable speeds. Thoracic vagal cooling, extending up to 5 h, reversibly blocked gastric contractions induced by insulin hypoglycemia. Contractile waves were terminated at device temperatures of 2 degrees-6 degrees C but promptly returned with warming. Dogs were tranquil during denervation, and enclosed nerves remained functional for greater than 40 days.

Animals↗