Juan Cata - Academia.edu (original) (raw)

Papers by Juan Cata

Research paper thumbnail of Best practice in the administration of analgesia in postoncological surgery

Pain Management, 2015

SUMMARY The rationale for using multimodal analgesia after any major surgery is achievement of a... more SUMMARY The rationale for using multimodal analgesia after any major surgery is achievement of adequate analgesia while avoiding the unwanted effects of large doses of any analgesic, in particular opioids. There are two reasons why we can hypothesize that multimodal analgesia might have a significant impact on cancer-related outcomes in the context of oncological orthopedic surgery. First, because multimodal analgesia is a key component of enhanced-recovery pathways and can accelerate return to intended oncological therapy. And second, because some of the analgesic used in multimodal analgesia (i.e., COX inhibitors, local analgesics and dexamethasone) can induce apoptosis in cancer cells and/or diminish the inflammatory response during surgery which itself can facilitate tumor growth.

Research paper thumbnail of Potential Use of Natural Killer Cell Transfer Therapy in the Perioperative Period to Improve Oncologic Outcomes

Scientifica, 2015

Immune suppression after oncologic surgery is a common phenomenon. Several studies have demonstra... more Immune suppression after oncologic surgery is a common phenomenon. Several studies have demonstrated that it is associated with poor survival owing to cancer progression. Immunotherapy, especially NK cell transfer therapy, is an attractive alternative because current methodologies to isolate, generate, and expand NK cells have shown good safety profiles in current active investigations. We believe that the use of NK cell transfer therapy in the context of postoperative minimal residual disease deserves significant investigation.

Research paper thumbnail of Clinical and experimental finding in humans and animals with chemotherapy-induced peripheral neuropathy

Minerva anestesiologica

Pain arises from numerous causes in cancer patients. Well known to cancer care providers, but per... more Pain arises from numerous causes in cancer patients. Well known to cancer care providers, but perhaps less well so to others, is that the main causes of pain in cancer patients in fact arise due to cancer treatments more so than the disease itself. In this paper clinical and laboratory findings on the characteristics of chemotherapy-induced neuropathic pain are reviewed and a scheme for the underlying mechanisms is outlined.

Research paper thumbnail of Dexmedetomidine as sole sedative during percutaneous carotid artery stenting in a patient with severe chronic obstructive pulmonary disease

Minerva anestesiologica

Carotid artery ballooning and stenting is a percutaneous interventional therapy for the treatment... more Carotid artery ballooning and stenting is a percutaneous interventional therapy for the treatment of patients with atherosclerotic occlusive disease of the carotid artery. Patients with severe comorbidities are usually considered candidates for this procedure. The carotid artery stenting can be done under either general or strict local anesthesia, or alternatively by using a combination of intravenous sedation and local anesthesia. Dexmedetomidine is a selective alpha-adrenergic agent that has both sedative and analgesic properties but lacks a depressive effect on respiratory drive. This article describes the case of a patient with severe chronic obstructive pulmonary disease and severe carotid stenosis, who underwent carotid stenting under monitored anesthesia care with dexmedetomidine. Only one episode of bradycardia and hypotension was observed, and this was successfully treated with glycopyrrolate.

Research paper thumbnail of Chemotherapy-induced cardiovascular toxicity: beyond anthracyclines

Minerva anestesiologica, 2014

It is not uncommon for anesthesiologists to encounter cancer patients who have received chemother... more It is not uncommon for anesthesiologists to encounter cancer patients who have received chemotherapy agents known to cause cardiovascular toxicities such as heart failure, systemic hypertension and thromboembolic events. Anthracyclines have been for several decades the most studied agents because of their known cardiovascular effects and relatively high incidence of heart failure. However, cancer patients are currently treated with newer chemotherapeutics such as imatinib, sunitinib, trastuzumab and bevacizumab that are also responsible of causing cardiovascular toxicities. The type of cardiotoxicity associated with these newer agents (type II cardiotoxicity) appears to be different in terms of pathogenesis to that caused by anthracyclines (type I cardiotoxicity). Thus, anesthesiologist needs to be aware of the clinical features of each type of cardiac toxicity. This review will summarize the current clinical evidence on cardiovascular toxicity induced by chemotherapeutic agents and...

Research paper thumbnail of Spinal cord stimulation relieves chemotherapy-induced pain: a clinical case report

Journal of pain and symptom management, 2004

We present two patients with chemotherapy-induced painful neuropathy that had been poorly control... more We present two patients with chemotherapy-induced painful neuropathy that had been poorly controlled with medications but successfully treated with spinal cord stimulation (SCS). A trial period of SCS provided effective pain relief in both patients who subsequently underwent permanent stimulator implantation. Psychophysical tests were performed before and after the implantation of trial and permanent stimulators. SCS improved pain scores and facilitated a reduction of medications. Both patients reported improved gait and one of them also reported an increase in leg flexibility. Psychophysical tests demonstrated an improvement in touch and sharpness detection thresholds. In summary, SCS offers a therapeutic option for patients with chemotherapy-induced peripheral neuropathy who have poor pain relief with standard medical treatment.

Research paper thumbnail of Perioperative Clinical Interventions That Modify the Immune Response in Cancer Patients

Open Journal of Anesthesiology, 2013

The immune system plays a pivotal role against cancer. The development of a successful immune res... more The immune system plays a pivotal role against cancer. The development of a successful immune response involves the balance between the Th1 (antitumor) and Th2 (protumor) responses. Once this balance is lost, diseases such as cancer may become apparent. Surgical stress, volatile anaesthetics, opioids and blood transfusions are known to favour a Th2 response that manifests as immune suppression. During surgery the load of circulating malignant cancer cells is increased by tumour manipulation. These cancer cells can migrate and seed in distant tissues and form metastasis. Also, some cancer patients may present with micrometastasis that may become invasive if left untreated. Therefore, the perioperative period is a moment of immunological vulnerability in cancer patients. A better understanding of the factors that affect the Th1/Th2 balance may allow anaesthesiologists to identify patients at high risk for cancer recurrence. This review describes the perioperative interventions that can alter the Th1/Th2 balance, during the perioperative period of oncological surgery.

Research paper thumbnail of Postoperative acute pain

Anesthesia for Spine Surgery, 2012

Research paper thumbnail of Effect of Fenoldopam on Ischemia/Reperfusion-Induced Apoptosis

Renal Failure, 2006

Recently we demonstrated the effect of fenoldopam on ischemia/reperfusion (I/R) induced NFkappaB ... more Recently we demonstrated the effect of fenoldopam on ischemia/reperfusion (I/R) induced NFkappaB mediated pro-inflammatory signal transduction. However, the effect of fenoldopam on I/R-induced apoptosis is not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that fenoldopam attenuates I/R-induced apoptosis. Sprague-Dawley rats were anesthetized by intraperitoneal administration of 50 mg/kg urethane and randomly allocated into 4 groups (n=6 each): (1) sham-operated, (2) sham operation with infusion of 0.1 microg/kg/min fenoldopam, (3) unilateral renal ischemia followed by 4 h of reperfusion, and (4) I/R with fenoldopam infusion. Kidney samples were fixed and paraffin-embedded to measure apoptosis. Data were compared between groups using ANOVA with Bonferroni correction. RNA was extracted from each left kidney to probe cDNA microarray and measure gene expression as percent of positive control. Compared to the control group, I/R significantly (P < 0.001) induced apoptosis in both the cortex and medulla. Similarly, microarray analysis revealed that IR induced 73 apoptosis-related genes. Treatment with fenoldopam significantly reduced (P < 0.001) I/R-induced apoptosis both in the cortex and medulla and attenuated all 73 I/R-induced apoptosis-related genes. Data from this rat model of ischemic nephropathy suggest that fenoldopam may attenuate I/R-induced apoptosis and apoptosis-related gene transcription.

Research paper thumbnail of Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients

Pain, 2004

Taxol produces neuropathic pain with three distinct zones of involvement in the extremities. Most... more Taxol produces neuropathic pain with three distinct zones of involvement in the extremities. Most distally is an area of on-going pain and proximal to this is a zone of sensory disturbance but not overt pain. These two areas were confined in all but one case to the glabrous skin of the hands and/or feet. More proximal is an area not recognized by the patients as involved with pain or sensory disturbance yet wherein quantitative sensory tests nevertheless reveal altered sensibility. Impairment of perception to light touch, normally conveyed by myelinated fibers, was dramatically altered in all three areas, being approximately 50-fold greater than normal in areas of pain and sensory disturbance as well as in areas of skin perceived by the patients as not affected. Impairment of perception to sharpness, normally conveyed by small myelinated fibers, was most pronounced in areas of on-going pain, intermediate in areas of sensory disturbance and near baseline in more proximal skin of chemotherapy patients. In contrast to mechanical sensibility, thermal thresholds for warm and heat pain detection were normal throughout. Finally, chemotherapy patients showed paradoxical burning pain to skin cooling that was most pronounced in proximal areas of skin thought to be unaffected by the patients, intermediate in the border zone of altered sensibility and least pronounced in areas of on-going pain. These data suggest that taxol produces a neuropathy characterized by pronounced impairment of function in A-beta myelinated fibers, intermediate impairment of A-delta myelinated fibers, and a relative sparing of C-fibers.

Research paper thumbnail of Spinal injection of IL-2 or IL-15 alters mechanical and thermal withdrawal thresholds in rats

Neuroscience Letters, 2008

IL-2 and IL-15 were tested for effects on responses to mechanical or thermal stimuli when spinall... more IL-2 and IL-15 were tested for effects on responses to mechanical or thermal stimuli when spinally administered to male Sprague-Dawley rats with surgically implanted intrathecal catheters. Restricted doses of both IL-2 and IL-15 produced increased responsiveness to mechanical stimulation of the hindpaws. This effect lasted up to 48 hours. IL-2 had biphasic effects on thermal responses whereas IL-15 produced thermal hypalgesia alone. These effects dissipated within 24 hours. These results suggest that IL-2 and IL-15 may participate in the generation of hyperalgesia in some pain conditions.

Research paper thumbnail of Spinal glial glutamate transporters downregulate in rats with taxol-induced hyperalgesia

Neuroscience Letters, 2005

Changes in the expression of glial glutamate transporters (GLAST and GLT-1) were examined in the ... more Changes in the expression of glial glutamate transporters (GLAST and GLT-1) were examined in the spinal cord of rats with chemotherapy (taxol)-induced mechanical hyperalgesia. Immunohistochemical studies show that the expression of both GLAST and GLT-1 in the L4-L5 spinal dorsal horn is decreased by 24% (P < 0.001) and 23% (P < 0.001), respectively, in rats with taxol-induced hyperalgesia as compared with those in control rats. These changes were further confirmed using an enzyme-linked immunosorbent assay that confirmed downregulation of GLAST by 36% (P < 0.05) and GLT-1 by 18% (P < 0.05) in the L4-L5 spinal cord of taxol-treated rats. These data indicate that downregulation of glutamate transporters may contribute to the development of hyperalgesia induced by taxol and suggest that glutamate transporters may be a new target for treatment of pain.

Research paper thumbnail of Altered discharges of spinal wide dynamic range neurons and down-regulation of glutamate transporter expression in rats with paclitaxel-induced hyperalgesia

Neuroscience, 2006

Changes in the signaling of wide dynamic range neurons and the expression of glutamate transporte... more Changes in the signaling of wide dynamic range neurons and the expression of glutamate transporters in the lumbar spinal dorsal horn of rats with Taxol-induced hyperalgesia are detailed in this report. Deep spinal lamina neurons have significantly increased spontaneous activity and after-discharges to noxious mechanical stimuli, increased responses to both skin heating and cooling, and increased after-discharges and abnormal windup to transcutaneous electrical stimuli. The expression of glutamate transporter proteins in the dorsal horn is decreased at the time point corresponding to the physiological changes. These results suggest a state of increased excitability develops in spinal pain-signaling neurons as a consequence of decreased glutamate clearance. These changes in dorsal horn neurobiology likely in turn contribute to the hyper-responsiveness to sensory stimuli seen in animals treated with Taxol and may play a role in the pain seen in cancer patients receiving Taxol.

Research paper thumbnail of Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and increased responses of spinal dorsal horn neurons to peripheral afferent stimulation

Neuroscience, 2006

Glutamate is a primary excitatory neurotransmitter in the mammalian CNS. Glutamate released from ... more Glutamate is a primary excitatory neurotransmitter in the mammalian CNS. Glutamate released from presynaptic neurons is cleared from the synaptic cleft passively by diffusion and actively by glutamate transporters. In this study, the role of glutamate transporters in sensory processing in the spinal cord has been investigated in behavioral, in vivo and in vitro experiments. Intrathecal application of a non-selective glutamate transport inhibitor, L-trans-pyrrolidine-2,4-dicarboxylic acid (10 l of 100 M solution) induced hypersensitivity to peripheral mechanical and thermal stimuli. Topical application of L-trans-pyrrolidine-2,4-dicarboxylic acid (100 M) onto the dorsal surface of the L3-L6 spinal cord increased spontaneous activities, innocuous and noxious stimulusevoked responses and after-discharges of wide dynamic range neurons in the L4 -5 spinal segments. Whole cell recordings made from superficial dorsal horn neurons in an isolated whole spinal cord from newborn rats (2-3 weeks old) revealed that bath-applied L-trans-pyrrolidine-2,4-dicarboxylic acid (100 M) produced partial membrane depolarization, increased spontaneous action potentials with decreased neuronal membrane resistance and time constant, but without significant changes of capacitance. Finally, the amplitude and duration of primary afferent evoked-excitatory postsynaptic currents recorded from neurons in the substantia gelatinosa in the spinal slices from young adult rats (6 -8 weeks old) were increased in the presence of L-trans-pyrrolidine-2,4dicarboxylic acid (100 M). This study indicates that glutamate transporters regulate baseline excitability and responses of dorsal horn neurons to peripheral stimulation, and suggests that dysfunction of glutamate transporters may contribute to certain types of pathological pain. © 2005 Published by Elsevier Ltd on behalf of IBRO.

Research paper thumbnail of Spinal cord stimulation relieves chemotherapy-induced pain: a clinical case report

Journal of Pain and Symptom Management, 2004

peripheral neuropathy who have poor pain relief with standard medical treatment. J Pain Symptom M... more peripheral neuropathy who have poor pain relief with standard medical treatment. J Pain Symptom Manage 2004;27:72-78. Ć 2004 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Research paper thumbnail of Dysfunction in Multiple Primary Afferent Fiber Subtypes Revealed By Quantitative Sensory Testing in Patients with Chronic Vincristine-Induced Pain

Journal of Pain and Symptom Management, 2007

Vincristine is one of the frontline chemotherapy drugs for the treatment of numerous lymphoid neo... more Vincristine is one of the frontline chemotherapy drugs for the treatment of numerous lymphoid neoplasias. The main dose-limiting complication of vincristine is the development of painful peripheral neuropathy. Although clinical reports have appeared in the literature detailing the symptoms of vincristine neuropathy, quantitative sensory testing data that might yield insight to dysfunction in subsets of primary afferents are lacking. In this report, pain descriptors and anatomical distributions of sensory abnormalities were collected in each patient. Touch detection threshold, sharpness detection threshold, the thresholds for the detection of skin warming, heat pain, skin cooling, and the perception of cooling-induced pain were measured in patients with chronic vincristine-induced pain in each area of sensory abnormality and in skin perceived as outside the affected areas. Elevated touch detection thresholds were observed both within and outside areas affected by pain and sensory abnormality. Elevated sharpness and warm detection thresholds were noted only in areas affected by pain. These data suggest that chronic vincristine-induced pain is associated with dysfunction in Ab, Ad, and C caliber primary afferent fibers. Deficits in Ab fibers appear to precede and presage deficits in the other fiber types, whereas deficits in Ad-and C-fiber function appear to be specifically associated with the generation of pain. J Pain Symptom Manage 2007;33:166e179. Ó

Research paper thumbnail of Quantitative Sensory Findings in Patients With Bortezomib-Induced Pain

The Journal of Pain, 2007

promising antineoplastic effects against a variety of neoplasias. Neuropathic pain is emerging as... more promising antineoplastic effects against a variety of neoplasias. Neuropathic pain is emerging as a major complication of bortezomib. Although clinical reports have appeared in the literature describing the general symptoms of bortezomib chemoneuropathy, specific quantitative sensory data that detail the sensory deficits that might yield insight to the primary afferent dysfunction contributing to this pain is lacking. In this report, it is shown that patients with bortezomib-induced neuropathic pain have significantly elevated touch detection threshold and slotted peg board time, impaired sharpness detection, and elevated thresholds for the detection of skin warming and heat pain. Patients also had increased reports of cold pain. These data indicate that bortezomib-induced neuropathy is associated with deficits in A␤, A␦, and C caliber primary afferent fibers.

Research paper thumbnail of Follow-Up Psychophysical Studies in Bortezomib-Related Chemoneuropathy Patients

The Journal of Pain, 2011

Many frontline chemotherapeutic agents produce robust neuropathy as a dose-limiting side effect; ... more Many frontline chemotherapeutic agents produce robust neuropathy as a dose-limiting side effect; however, the persistence of chemotherapy-related sensory disturbances and pain are not welldocumented. We have previously investigated the qualities of bortezomib-induced pain, and now seek to determine the ongoing nature of this pain. Twenty-six control subjects and eleven patients who had previously been treated with bortezomib and who were experiencing ongoing pain consented to recurring quantitative sensory testing. A pilot immunohistochemistry study of skin innervation was also performed on patient obtained biopsies. Psychophysical testing in patients revealed persistent changes including decreased skin temperature in the area of pain, diminished touch and sharpness detection, increased pegboard completion times, and decreased sensitivity to skin heating. Additionally, the intensity of pain, as captured by the use of a visual analog scale and pain descriptors, was reported by patients to be unchanged during the retest despite similar morphine equivalent daily doses. The patient skin biopsies displayed a marked decrease in the density of epidermal nerve fibers and Meissner's corpuscles. These results signify a persistent and severe impairment of Aβ, Aδ, and C fibers in patients with chronic bortezomib-induced chemoneuropathy. Further, this study reports a loss of both epidermal nerve fibers and Meissner's corpuscles.

Research paper thumbnail of Ghrelin Prevents Cisplatin-Induced Mechanical Hyperalgesia and Cachexia

Endocrinology, 2008

Complications induced by the chemotherapeutic agent cisplatin, such as neuropathy and cachexia, o... more Complications induced by the chemotherapeutic agent cisplatin, such as neuropathy and cachexia, occur frequently, are often dose limiting, and have an impact on quality of life and survival in cancer patients. The recently discovered hormone ghrelin is a potent GH secretagogue with orexigenic and neuroprotective properties that may prevent or ameliorate these complications. The objective of this study was to determine the effects of ghrelin administration on mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Adult male Sprague-Dawley rats were given cisplatin, ghrelin, ghrelin-cisplatin, or vehicle ip. Food intake and body weight were measured daily. Behavioral tests to assess the development of hyperalgesia were conducted by measuring mechanical and thermal sensitivity. Plasma ghrelin and IGF-I levels were also measured. Our results indicate that ghrelin coad-ministration inhibited the development of cisplatin-induced mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Although ghrelin treatment had no effect on plasma IGF-I levels in control rats, it prevented the decrease in IGF-I levels induced by cisplatin. The attenuation of cisplatin-induced mechanical hyperalgesia induced by ghrelin was correlated with the prevention of cisplatin-induced lowering of IGF-I. In conclusion, ghrelin administration may be useful in the treatment or prevention of chemotherapy induced neuropathy and cachexia. Attenuation of mechanical hyperalgesia in the rat by the hormone ghrelin provides a unique model for elucidating the mechanisms involved, which are essential toward our understanding of these complications. (Endocrinology 149: 455-460, 2008)

Research paper thumbnail of Effect of General Anesthetics on Renal Cell Apoptosis and Apoptotic Signal Transduction in Rat Kidney

Critical Care Medicine, 2005

Methods: Adult male Sprague-Dawley rats were ran-domly divided into 4 groups:(a) control, non-ane... more Methods: Adult male Sprague-Dawley rats were ran-domly divided into 4 groups:(a) control, non-anesthetized rats (n= 3), rats anes-thetized with (b) inhaled isoflurane (n= 6),(c) intraperitoneal pentobarbital (n= 6), and (d) intraperitoneal urethane (n= 6). Animals were ...

Research paper thumbnail of Best practice in the administration of analgesia in postoncological surgery

Pain Management, 2015

SUMMARY The rationale for using multimodal analgesia after any major surgery is achievement of a... more SUMMARY The rationale for using multimodal analgesia after any major surgery is achievement of adequate analgesia while avoiding the unwanted effects of large doses of any analgesic, in particular opioids. There are two reasons why we can hypothesize that multimodal analgesia might have a significant impact on cancer-related outcomes in the context of oncological orthopedic surgery. First, because multimodal analgesia is a key component of enhanced-recovery pathways and can accelerate return to intended oncological therapy. And second, because some of the analgesic used in multimodal analgesia (i.e., COX inhibitors, local analgesics and dexamethasone) can induce apoptosis in cancer cells and/or diminish the inflammatory response during surgery which itself can facilitate tumor growth.

Research paper thumbnail of Potential Use of Natural Killer Cell Transfer Therapy in the Perioperative Period to Improve Oncologic Outcomes

Scientifica, 2015

Immune suppression after oncologic surgery is a common phenomenon. Several studies have demonstra... more Immune suppression after oncologic surgery is a common phenomenon. Several studies have demonstrated that it is associated with poor survival owing to cancer progression. Immunotherapy, especially NK cell transfer therapy, is an attractive alternative because current methodologies to isolate, generate, and expand NK cells have shown good safety profiles in current active investigations. We believe that the use of NK cell transfer therapy in the context of postoperative minimal residual disease deserves significant investigation.

Research paper thumbnail of Clinical and experimental finding in humans and animals with chemotherapy-induced peripheral neuropathy

Minerva anestesiologica

Pain arises from numerous causes in cancer patients. Well known to cancer care providers, but per... more Pain arises from numerous causes in cancer patients. Well known to cancer care providers, but perhaps less well so to others, is that the main causes of pain in cancer patients in fact arise due to cancer treatments more so than the disease itself. In this paper clinical and laboratory findings on the characteristics of chemotherapy-induced neuropathic pain are reviewed and a scheme for the underlying mechanisms is outlined.

Research paper thumbnail of Dexmedetomidine as sole sedative during percutaneous carotid artery stenting in a patient with severe chronic obstructive pulmonary disease

Minerva anestesiologica

Carotid artery ballooning and stenting is a percutaneous interventional therapy for the treatment... more Carotid artery ballooning and stenting is a percutaneous interventional therapy for the treatment of patients with atherosclerotic occlusive disease of the carotid artery. Patients with severe comorbidities are usually considered candidates for this procedure. The carotid artery stenting can be done under either general or strict local anesthesia, or alternatively by using a combination of intravenous sedation and local anesthesia. Dexmedetomidine is a selective alpha-adrenergic agent that has both sedative and analgesic properties but lacks a depressive effect on respiratory drive. This article describes the case of a patient with severe chronic obstructive pulmonary disease and severe carotid stenosis, who underwent carotid stenting under monitored anesthesia care with dexmedetomidine. Only one episode of bradycardia and hypotension was observed, and this was successfully treated with glycopyrrolate.

Research paper thumbnail of Chemotherapy-induced cardiovascular toxicity: beyond anthracyclines

Minerva anestesiologica, 2014

It is not uncommon for anesthesiologists to encounter cancer patients who have received chemother... more It is not uncommon for anesthesiologists to encounter cancer patients who have received chemotherapy agents known to cause cardiovascular toxicities such as heart failure, systemic hypertension and thromboembolic events. Anthracyclines have been for several decades the most studied agents because of their known cardiovascular effects and relatively high incidence of heart failure. However, cancer patients are currently treated with newer chemotherapeutics such as imatinib, sunitinib, trastuzumab and bevacizumab that are also responsible of causing cardiovascular toxicities. The type of cardiotoxicity associated with these newer agents (type II cardiotoxicity) appears to be different in terms of pathogenesis to that caused by anthracyclines (type I cardiotoxicity). Thus, anesthesiologist needs to be aware of the clinical features of each type of cardiac toxicity. This review will summarize the current clinical evidence on cardiovascular toxicity induced by chemotherapeutic agents and...

Research paper thumbnail of Spinal cord stimulation relieves chemotherapy-induced pain: a clinical case report

Journal of pain and symptom management, 2004

We present two patients with chemotherapy-induced painful neuropathy that had been poorly control... more We present two patients with chemotherapy-induced painful neuropathy that had been poorly controlled with medications but successfully treated with spinal cord stimulation (SCS). A trial period of SCS provided effective pain relief in both patients who subsequently underwent permanent stimulator implantation. Psychophysical tests were performed before and after the implantation of trial and permanent stimulators. SCS improved pain scores and facilitated a reduction of medications. Both patients reported improved gait and one of them also reported an increase in leg flexibility. Psychophysical tests demonstrated an improvement in touch and sharpness detection thresholds. In summary, SCS offers a therapeutic option for patients with chemotherapy-induced peripheral neuropathy who have poor pain relief with standard medical treatment.

Research paper thumbnail of Perioperative Clinical Interventions That Modify the Immune Response in Cancer Patients

Open Journal of Anesthesiology, 2013

The immune system plays a pivotal role against cancer. The development of a successful immune res... more The immune system plays a pivotal role against cancer. The development of a successful immune response involves the balance between the Th1 (antitumor) and Th2 (protumor) responses. Once this balance is lost, diseases such as cancer may become apparent. Surgical stress, volatile anaesthetics, opioids and blood transfusions are known to favour a Th2 response that manifests as immune suppression. During surgery the load of circulating malignant cancer cells is increased by tumour manipulation. These cancer cells can migrate and seed in distant tissues and form metastasis. Also, some cancer patients may present with micrometastasis that may become invasive if left untreated. Therefore, the perioperative period is a moment of immunological vulnerability in cancer patients. A better understanding of the factors that affect the Th1/Th2 balance may allow anaesthesiologists to identify patients at high risk for cancer recurrence. This review describes the perioperative interventions that can alter the Th1/Th2 balance, during the perioperative period of oncological surgery.

Research paper thumbnail of Postoperative acute pain

Anesthesia for Spine Surgery, 2012

Research paper thumbnail of Effect of Fenoldopam on Ischemia/Reperfusion-Induced Apoptosis

Renal Failure, 2006

Recently we demonstrated the effect of fenoldopam on ischemia/reperfusion (I/R) induced NFkappaB ... more Recently we demonstrated the effect of fenoldopam on ischemia/reperfusion (I/R) induced NFkappaB mediated pro-inflammatory signal transduction. However, the effect of fenoldopam on I/R-induced apoptosis is not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that fenoldopam attenuates I/R-induced apoptosis. Sprague-Dawley rats were anesthetized by intraperitoneal administration of 50 mg/kg urethane and randomly allocated into 4 groups (n=6 each): (1) sham-operated, (2) sham operation with infusion of 0.1 microg/kg/min fenoldopam, (3) unilateral renal ischemia followed by 4 h of reperfusion, and (4) I/R with fenoldopam infusion. Kidney samples were fixed and paraffin-embedded to measure apoptosis. Data were compared between groups using ANOVA with Bonferroni correction. RNA was extracted from each left kidney to probe cDNA microarray and measure gene expression as percent of positive control. Compared to the control group, I/R significantly (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) induced apoptosis in both the cortex and medulla. Similarly, microarray analysis revealed that IR induced 73 apoptosis-related genes. Treatment with fenoldopam significantly reduced (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) I/R-induced apoptosis both in the cortex and medulla and attenuated all 73 I/R-induced apoptosis-related genes. Data from this rat model of ischemic nephropathy suggest that fenoldopam may attenuate I/R-induced apoptosis and apoptosis-related gene transcription.

Research paper thumbnail of Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients

Pain, 2004

Taxol produces neuropathic pain with three distinct zones of involvement in the extremities. Most... more Taxol produces neuropathic pain with three distinct zones of involvement in the extremities. Most distally is an area of on-going pain and proximal to this is a zone of sensory disturbance but not overt pain. These two areas were confined in all but one case to the glabrous skin of the hands and/or feet. More proximal is an area not recognized by the patients as involved with pain or sensory disturbance yet wherein quantitative sensory tests nevertheless reveal altered sensibility. Impairment of perception to light touch, normally conveyed by myelinated fibers, was dramatically altered in all three areas, being approximately 50-fold greater than normal in areas of pain and sensory disturbance as well as in areas of skin perceived by the patients as not affected. Impairment of perception to sharpness, normally conveyed by small myelinated fibers, was most pronounced in areas of on-going pain, intermediate in areas of sensory disturbance and near baseline in more proximal skin of chemotherapy patients. In contrast to mechanical sensibility, thermal thresholds for warm and heat pain detection were normal throughout. Finally, chemotherapy patients showed paradoxical burning pain to skin cooling that was most pronounced in proximal areas of skin thought to be unaffected by the patients, intermediate in the border zone of altered sensibility and least pronounced in areas of on-going pain. These data suggest that taxol produces a neuropathy characterized by pronounced impairment of function in A-beta myelinated fibers, intermediate impairment of A-delta myelinated fibers, and a relative sparing of C-fibers.

Research paper thumbnail of Spinal injection of IL-2 or IL-15 alters mechanical and thermal withdrawal thresholds in rats

Neuroscience Letters, 2008

IL-2 and IL-15 were tested for effects on responses to mechanical or thermal stimuli when spinall... more IL-2 and IL-15 were tested for effects on responses to mechanical or thermal stimuli when spinally administered to male Sprague-Dawley rats with surgically implanted intrathecal catheters. Restricted doses of both IL-2 and IL-15 produced increased responsiveness to mechanical stimulation of the hindpaws. This effect lasted up to 48 hours. IL-2 had biphasic effects on thermal responses whereas IL-15 produced thermal hypalgesia alone. These effects dissipated within 24 hours. These results suggest that IL-2 and IL-15 may participate in the generation of hyperalgesia in some pain conditions.

Research paper thumbnail of Spinal glial glutamate transporters downregulate in rats with taxol-induced hyperalgesia

Neuroscience Letters, 2005

Changes in the expression of glial glutamate transporters (GLAST and GLT-1) were examined in the ... more Changes in the expression of glial glutamate transporters (GLAST and GLT-1) were examined in the spinal cord of rats with chemotherapy (taxol)-induced mechanical hyperalgesia. Immunohistochemical studies show that the expression of both GLAST and GLT-1 in the L4-L5 spinal dorsal horn is decreased by 24% (P < 0.001) and 23% (P < 0.001), respectively, in rats with taxol-induced hyperalgesia as compared with those in control rats. These changes were further confirmed using an enzyme-linked immunosorbent assay that confirmed downregulation of GLAST by 36% (P < 0.05) and GLT-1 by 18% (P < 0.05) in the L4-L5 spinal cord of taxol-treated rats. These data indicate that downregulation of glutamate transporters may contribute to the development of hyperalgesia induced by taxol and suggest that glutamate transporters may be a new target for treatment of pain.

Research paper thumbnail of Altered discharges of spinal wide dynamic range neurons and down-regulation of glutamate transporter expression in rats with paclitaxel-induced hyperalgesia

Neuroscience, 2006

Changes in the signaling of wide dynamic range neurons and the expression of glutamate transporte... more Changes in the signaling of wide dynamic range neurons and the expression of glutamate transporters in the lumbar spinal dorsal horn of rats with Taxol-induced hyperalgesia are detailed in this report. Deep spinal lamina neurons have significantly increased spontaneous activity and after-discharges to noxious mechanical stimuli, increased responses to both skin heating and cooling, and increased after-discharges and abnormal windup to transcutaneous electrical stimuli. The expression of glutamate transporter proteins in the dorsal horn is decreased at the time point corresponding to the physiological changes. These results suggest a state of increased excitability develops in spinal pain-signaling neurons as a consequence of decreased glutamate clearance. These changes in dorsal horn neurobiology likely in turn contribute to the hyper-responsiveness to sensory stimuli seen in animals treated with Taxol and may play a role in the pain seen in cancer patients receiving Taxol.

Research paper thumbnail of Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and increased responses of spinal dorsal horn neurons to peripheral afferent stimulation

Neuroscience, 2006

Glutamate is a primary excitatory neurotransmitter in the mammalian CNS. Glutamate released from ... more Glutamate is a primary excitatory neurotransmitter in the mammalian CNS. Glutamate released from presynaptic neurons is cleared from the synaptic cleft passively by diffusion and actively by glutamate transporters. In this study, the role of glutamate transporters in sensory processing in the spinal cord has been investigated in behavioral, in vivo and in vitro experiments. Intrathecal application of a non-selective glutamate transport inhibitor, L-trans-pyrrolidine-2,4-dicarboxylic acid (10 l of 100 M solution) induced hypersensitivity to peripheral mechanical and thermal stimuli. Topical application of L-trans-pyrrolidine-2,4-dicarboxylic acid (100 M) onto the dorsal surface of the L3-L6 spinal cord increased spontaneous activities, innocuous and noxious stimulusevoked responses and after-discharges of wide dynamic range neurons in the L4 -5 spinal segments. Whole cell recordings made from superficial dorsal horn neurons in an isolated whole spinal cord from newborn rats (2-3 weeks old) revealed that bath-applied L-trans-pyrrolidine-2,4-dicarboxylic acid (100 M) produced partial membrane depolarization, increased spontaneous action potentials with decreased neuronal membrane resistance and time constant, but without significant changes of capacitance. Finally, the amplitude and duration of primary afferent evoked-excitatory postsynaptic currents recorded from neurons in the substantia gelatinosa in the spinal slices from young adult rats (6 -8 weeks old) were increased in the presence of L-trans-pyrrolidine-2,4dicarboxylic acid (100 M). This study indicates that glutamate transporters regulate baseline excitability and responses of dorsal horn neurons to peripheral stimulation, and suggests that dysfunction of glutamate transporters may contribute to certain types of pathological pain. © 2005 Published by Elsevier Ltd on behalf of IBRO.

Research paper thumbnail of Spinal cord stimulation relieves chemotherapy-induced pain: a clinical case report

Journal of Pain and Symptom Management, 2004

peripheral neuropathy who have poor pain relief with standard medical treatment. J Pain Symptom M... more peripheral neuropathy who have poor pain relief with standard medical treatment. J Pain Symptom Manage 2004;27:72-78. Ć 2004 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Research paper thumbnail of Dysfunction in Multiple Primary Afferent Fiber Subtypes Revealed By Quantitative Sensory Testing in Patients with Chronic Vincristine-Induced Pain

Journal of Pain and Symptom Management, 2007

Vincristine is one of the frontline chemotherapy drugs for the treatment of numerous lymphoid neo... more Vincristine is one of the frontline chemotherapy drugs for the treatment of numerous lymphoid neoplasias. The main dose-limiting complication of vincristine is the development of painful peripheral neuropathy. Although clinical reports have appeared in the literature detailing the symptoms of vincristine neuropathy, quantitative sensory testing data that might yield insight to dysfunction in subsets of primary afferents are lacking. In this report, pain descriptors and anatomical distributions of sensory abnormalities were collected in each patient. Touch detection threshold, sharpness detection threshold, the thresholds for the detection of skin warming, heat pain, skin cooling, and the perception of cooling-induced pain were measured in patients with chronic vincristine-induced pain in each area of sensory abnormality and in skin perceived as outside the affected areas. Elevated touch detection thresholds were observed both within and outside areas affected by pain and sensory abnormality. Elevated sharpness and warm detection thresholds were noted only in areas affected by pain. These data suggest that chronic vincristine-induced pain is associated with dysfunction in Ab, Ad, and C caliber primary afferent fibers. Deficits in Ab fibers appear to precede and presage deficits in the other fiber types, whereas deficits in Ad-and C-fiber function appear to be specifically associated with the generation of pain. J Pain Symptom Manage 2007;33:166e179. Ó

Research paper thumbnail of Quantitative Sensory Findings in Patients With Bortezomib-Induced Pain

The Journal of Pain, 2007

promising antineoplastic effects against a variety of neoplasias. Neuropathic pain is emerging as... more promising antineoplastic effects against a variety of neoplasias. Neuropathic pain is emerging as a major complication of bortezomib. Although clinical reports have appeared in the literature describing the general symptoms of bortezomib chemoneuropathy, specific quantitative sensory data that detail the sensory deficits that might yield insight to the primary afferent dysfunction contributing to this pain is lacking. In this report, it is shown that patients with bortezomib-induced neuropathic pain have significantly elevated touch detection threshold and slotted peg board time, impaired sharpness detection, and elevated thresholds for the detection of skin warming and heat pain. Patients also had increased reports of cold pain. These data indicate that bortezomib-induced neuropathy is associated with deficits in A␤, A␦, and C caliber primary afferent fibers.

Research paper thumbnail of Follow-Up Psychophysical Studies in Bortezomib-Related Chemoneuropathy Patients

The Journal of Pain, 2011

Many frontline chemotherapeutic agents produce robust neuropathy as a dose-limiting side effect; ... more Many frontline chemotherapeutic agents produce robust neuropathy as a dose-limiting side effect; however, the persistence of chemotherapy-related sensory disturbances and pain are not welldocumented. We have previously investigated the qualities of bortezomib-induced pain, and now seek to determine the ongoing nature of this pain. Twenty-six control subjects and eleven patients who had previously been treated with bortezomib and who were experiencing ongoing pain consented to recurring quantitative sensory testing. A pilot immunohistochemistry study of skin innervation was also performed on patient obtained biopsies. Psychophysical testing in patients revealed persistent changes including decreased skin temperature in the area of pain, diminished touch and sharpness detection, increased pegboard completion times, and decreased sensitivity to skin heating. Additionally, the intensity of pain, as captured by the use of a visual analog scale and pain descriptors, was reported by patients to be unchanged during the retest despite similar morphine equivalent daily doses. The patient skin biopsies displayed a marked decrease in the density of epidermal nerve fibers and Meissner's corpuscles. These results signify a persistent and severe impairment of Aβ, Aδ, and C fibers in patients with chronic bortezomib-induced chemoneuropathy. Further, this study reports a loss of both epidermal nerve fibers and Meissner's corpuscles.

Research paper thumbnail of Ghrelin Prevents Cisplatin-Induced Mechanical Hyperalgesia and Cachexia

Endocrinology, 2008

Complications induced by the chemotherapeutic agent cisplatin, such as neuropathy and cachexia, o... more Complications induced by the chemotherapeutic agent cisplatin, such as neuropathy and cachexia, occur frequently, are often dose limiting, and have an impact on quality of life and survival in cancer patients. The recently discovered hormone ghrelin is a potent GH secretagogue with orexigenic and neuroprotective properties that may prevent or ameliorate these complications. The objective of this study was to determine the effects of ghrelin administration on mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Adult male Sprague-Dawley rats were given cisplatin, ghrelin, ghrelin-cisplatin, or vehicle ip. Food intake and body weight were measured daily. Behavioral tests to assess the development of hyperalgesia were conducted by measuring mechanical and thermal sensitivity. Plasma ghrelin and IGF-I levels were also measured. Our results indicate that ghrelin coad-ministration inhibited the development of cisplatin-induced mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Although ghrelin treatment had no effect on plasma IGF-I levels in control rats, it prevented the decrease in IGF-I levels induced by cisplatin. The attenuation of cisplatin-induced mechanical hyperalgesia induced by ghrelin was correlated with the prevention of cisplatin-induced lowering of IGF-I. In conclusion, ghrelin administration may be useful in the treatment or prevention of chemotherapy induced neuropathy and cachexia. Attenuation of mechanical hyperalgesia in the rat by the hormone ghrelin provides a unique model for elucidating the mechanisms involved, which are essential toward our understanding of these complications. (Endocrinology 149: 455-460, 2008)

Research paper thumbnail of Effect of General Anesthetics on Renal Cell Apoptosis and Apoptotic Signal Transduction in Rat Kidney

Critical Care Medicine, 2005

Methods: Adult male Sprague-Dawley rats were ran-domly divided into 4 groups:(a) control, non-ane... more Methods: Adult male Sprague-Dawley rats were ran-domly divided into 4 groups:(a) control, non-anesthetized rats (n= 3), rats anes-thetized with (b) inhaled isoflurane (n= 6),(c) intraperitoneal pentobarbital (n= 6), and (d) intraperitoneal urethane (n= 6). Animals were ...