Neuropathic ocular pain: an important yet underevaluated feature of dry eye.

Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eye-associated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain.

Gases and volatile compounds associated with micro-organisms in blown pack spoilage of Brazilian vacuum-packed beef.

UNLABELLED: This study correlated the composition of the spoilage bacterial flora with the main gaseous and volatile organic compounds (VOCs) found in the package headspace of spoiled, chilled, vacuum-packed meat. Fifteen chilled, vacuum-packed beef samples, suffering from blown pack spoilage, were studied using 16S rRNA clone sequencing. More than 50% of the bacteria were identified as lactic acid bacteria (LAB), followed by clostridia and enterobacteria. Fifty-one volatile compounds were detected in the spoiled samples. Although the major spoilage compounds were identified as alcohols and aldehydes, CO2 was identified as the major gas in the spoiled samples by headspace technique. Different species of bacteria contribute to different volatile compounds during meat spoilage. LAB played an important role in blown pack deterioration of the Brazilian beef studied. SIGNIFICANCE AND IMPACT OF THE STUDY: The data generated by this study provided useful information to correlate the microbial contamination of Enterobacteriaceae, lactic acid bacteria and Clostridium with the VOC and gaseous compound production to define, in a faster manner, not only the type of contamination, but also to prevent it.

Behavior of flavonols and carotenoids of minimally processed kale leaves during storage in passive modified atmosphere packaging.

Minimally processed kale leaves were packed in passive modified atmosphere and stored at 3 conditions: 1 °C in the dark and 11 °C with or without light exposure. The products were evaluated during storage in terms of headspace gas composition, sensory attributes, flavonol, and carotenoid contents. The sensory quality decreased slightly during 17 d at 1 °C in the dark. At 11 °C, the vegetable shelf life was predicted to be 6 d in the dark and 3 d with light. Quercetin and kaempferol were stable during storage for 15 d at 1 °C in the absence of light. At 11 °C in the dark, quercetin was stable during 10 d, increasing slightly on the 8th day. Kaempferol decreased up to the 5th day but increased on the 8th day, decreasing again on the 10th day. After 5 d at 11 °C under light, the flavonol levels were significantly higher than those of the initial values. Neoxanthin and violaxanthin did not change significantly after 15 d at 1 °C in the dark. Lutein and ß-carotene, however, decreased 7.1% and 11.3%, respectively. At 11 °C in the dark, neoxanthin, violaxanthin, lutein, and ß-carotene decreased 16.1%, 13.2%, 24.1%, and 23.7% after 10 d, respectively. At 11 °C under light, neoxanthin and lutein had a slight increase while violaxanthin and ß-carotene decreased 23.1% and 16.5% after 5 d. Practical Application: Passive modified atmosphere packaging together with refrigeration can extend the shelf life of minimally processed kale, retaining the health-promoting compounds, flavonols and carotenoids. Quercetin, kaempferol, neoxanthin, and violaxanthin are stable and lutein and ß-carotene slightly reduced.

ATP-sensitive potassium currents in rat primary afferent neurons: biophysical, pharmacological properties, and alterations by painful nerve injury.

ATP-sensitive potassium (K(ATP)) channels may be linked to mechanisms of pain after nerve injury, but remain under-investigated in primary afferents so far. We therefore characterized these channels in dorsal root ganglion (DRG) neurons, and tested whether they contribute to hyperalgesia after spinal nerve ligation (SNL). We compared K(ATP) channel properties between DRG somata classified by diameter into small or large, and by injury status into neurons from rats that either did or did not become hyperalgesic after SNL, or neurons from control animals. In cell-attached patches, we recorded basal K(ATP) channel opening in all neuronal subpopulations. However, higher open probabilities and longer open times were observed in large compared to small neurons. Following SNL, this channel activity was suppressed only in large neurons from hyperalgesic rats, but not from animals that did not develop hyperalgesia. In contrast, no alterations of channel activity developed in small neurons after axotomy. On the other hand, cell-free recordings showed similar ATP sensitivity, inward rectification and unitary conductance (70-80 pS) between neurons classified by size or injury status. Likewise, pharmacological sensitivity to the K(ATP) channel opener diazoxide, and to the selective blockers glibenclamide and tolbutamide, did not differ between groups. In large neurons, selective inhibition of whole-cell ATP-sensitive potassium channel current (I(K(ATP))) by glibenclamide depolarized resting membrane potential (RMP). The contribution of this current to RMP was also attenuated after painful axotomy. Using specific antibodies, we identified SUR1, SUR2, and Kir6.2 but not Kir6.1 subunits in DRGs. These findings indicate that functional K(ATP) channels are present in normal DRG neurons, wherein they regulate RMP. Alterations of these channels may be involved in the pathogenesis of neuropathic pain following peripheral nerve injury. Their biophysical and pharmacological properties are preserved even after axotomy, suggesting that K(ATP) channels in primary afferents remain available for therapeutic targeting against established neuropathic pain.

General versus neuraxial anaesthesia for caesarean section: impact on the duration of hospital stay.

We investigated retrospectively the duration of hospital stay of 1,619 women who received general (GA) (n = 582) or neuraxial anaesthesia (combined spinal-epidural [CSEA] (n = 614), epidural [EA] (n = 423)) for caesarean delivery over the years 2002-2005. Hospital stay was also analysed for the different obstetricians involved. Overall duration of hospital stay differed between 2002 and 2005 (p < 0.0001) but not between CSEA and EA (p = 0.460). Overall duration of hospital stay differed between neuraxial and GA group (p < 0.001). Duration of hospital stay of the GA group showed a progressive decrease between 2002 and 2005 (p = 0.002). Duration of hospital stay after neuraxial anaesthesia differed between 2002 and 2005 (p = 0.013) and among different surgeons (p < 0.001). Discharge rates from the hospital were shorter after neuraxial anaesthesia versus GA for the 3rd and 4th postoperative days (p < 0.001 and p < 0.001, respectively). Neuraxial anaesthesia for caesarean section seems to be associated with shorter duration of hospital stay than GA.

Acute postoperative pain predicts chronic pain and long-term analgesic requirements after breast surgery for cancer.

Postoperative pain and analgesic requirements may be associated with chronic pain. The aim of the study was to investigate this association. We studied 98 patients who had cancer breast surgery and served as controls in four previous studies, receiving placebo. We compared the pain and analgesic requirements 0-9 h and 1-6 days postoperatively: a) between patients with chronic pain 3 months postoperatively versus patients without and b) between those patients who consumed analgesics at home versus those who did not. Patients with chronic pain had experienced higher intensity pain at rest the first 9 postoperative hours (VAS-rest p = 0.033). Patients requiring analgesics at home had consumed postoperatively more opioids (p = 0.005) and more paracetamol (p = 0.037). These patients had experienced pain of higher intensity the first 9 postoperative hours (VAS-rest p = 0.022, VAS-movement p = 0.009) as well as during the six postoperative days (VAS-rest p = 0.013, VAS-movement p = 0.001). Higher intensities of acute postoperative pain are associated with chronic pain development. Higher analgesic needs and higher acute postoperatively pain intensity are associated with long-term analgesic consumption.

Local application of halothane, isoflurane or sevoflurane increases the response to an electrical stimulus in humans.

UNLABELLED: Volatile anesthetics may interfere with pain perception. This study investigates the effect of halothane, isoflurane and sevoflurane when applied locally, to the response of an electrical stimulus. METHODS: In this randomized control double-blind crossover study 70 volunteers were studied. In experiment 1 (30 subjects), equipotent liquid volumes of halothane 1 ml, isoflurane 1.5 ml and sevoflurane 2.7 ml were randomly applied on one forearm for 30 minutes. The other forearm received water. Both forearms were exposed to an electrical stimulus. The experiment was repeated the following day in a reverse fashion. In experiments 2 (20 subjects) and 3 (20 subjects) the response to the same stimulus was tested after local application of 2, 4, and 6 ml of halothane or 5 ml of sevoflurane respectively. RESULTS: Low doses of the three anesthetics were associated with an increased response to the electrical stimulus (F = 8.940, df = 1,174, P = 0.003). Higher doses of halothane and sevoflurane had no effect on the response (F = 2.358, df = 1,114, P = 0.127 and t = 0.840, df = 19, P = 0.411 respectively). CONCLUSIONS: Low liquid volumes of volatile anesthetics, when applied locally to the skin enhanced the response to an electrical stimulus but higher volumes had no effect.

A combination of gabapentin and local anaesthetics attenuates acute and late pain after abdominal hysterectomy.

BACKGROUND AND OBJECTIVE: Gabapentin and local anaesthetics may decrease postoperative pain and analgesic needs. The aim of the study was to investigate the effect of the combination of these drugs on the analgesic needs as well as on acute and late pain after abdominal hysterectomy. METHODS: Sixty patients undergoing abdominal hysterectomy were randomly assigned to receive postoperatively oral gabapentin 400 mg 6 hourly for 7 days plus continuous wound infusion of ropivacaine 0.75% for 30 h or placebo capsules identical to those of gabapentin for 7 days and continuous wound infusion of normal saline for 30 h. Morphine consumption (PCA) for 48 h, paracetamol 500 mg plus codeine 30 mg (Lonalgal tablets) intake on days 3-7, visual analogue pain scores at rest and after cough during the first 7 postoperative days, the need for analgesics at home and the presence and incidence of pain after 1 month were recorded. RESULTS: The treatment group consumed less cumulative morphine over the first 48 h (31 +/- 13.2 mg vs. 50 +/- 20.5 mg in controls, P < 0.001) and less Lonalgal tablets on days 3-7 (z = 2.54, P = 0.011). The visual analogue score values at rest and after cough did not differ between the groups during the first 7 postoperative days. One month postoperatively, fewer patients in the treatment group experienced pain due to surgery than in the control group (17/27 vs. 21/24, P = 0.045). CONCLUSION: Gabapentin and continuous wound infusion with ropivacaine 0.75% decreased analgesic needs and late pain in patients undergoing abdominal hysterectomy.

Pre-oxygenation enhances induction with sevoflurane as assessed using bispectral index monitoring.

BACKGROUND: Several methods may enhance the inhalational induction of anesthesia. In this randomized double-blind study, we evaluated the speed of induction of anesthesia with sevoflurane with or without pre-oxygenation. METHODS: Fifty-four patients scheduled for hysteroscopy received for 10 min air or 100% oxygen via a facemask followed by > or = 7% sevoflurane in 100% oxygen. During the first 300 s of sevoflurane administration, bispectral index (BIS) values were recorded every 30 s in all patients. In 14 patients, seven in each group, BIS, endtidal CO(2), tidal volume, respiratory rate, SpO(2), and heart rate were recorded every minute during the pre-induction period and every 30 s during the first 5 min of sevoflurane administration. RESULTS: The BIS, endtidal CO(2), tidal volume and respiratory rate did not differ between the oxygen or air breathing groups (P = 0.696, P = 0.999, P = 0.388, and P = 0.875, respectively), though the oxygen group exhibited lower tidal volumes by 16-20%. The SpO(2) and heart rates were higher in the oxygen breathing group (P < 0.001 and P = 0.042, respectively). During sevoflurane administration, BIS values were lower in the oxygen group vs. the group breathing air, in particular at 90, 120, 150, 180 and 210 s (P = 0.001, P = 0.001, P = 0.001, P = 0.001 and P = 0.030, respectively). The endtidal CO(2) and the tidal volumes between the groups did not differ. The two groups differed in the SpO(2) and the heart rates during induction (P = 0.004 and 0.003, respectively). CONCLUSIONS: Before sevoflurane administration, breathing 100% oxygen for 10 min enhances induction of anesthesia with sevoflurane.

Gabapentin attenuates late but not acute pain after abdominal hysterectomy.

BACKGROUND AND OBJECTIVE: Gabapentin has been suggested to decrease acute postoperative pain. We evaluated the effect of gabapentin on pain after abdominal hysterectomy. METHODS: Sixty patients scheduled for abdominal hysterectomy were randomized to receive orally gabapentin 400 mg 6 hourly or placebo. Treatment started 18 h preoperatively and continued for 5 postoperative days. Pain (visual analogue score) and consumption of morphine for 48 h and of oral paracetamol/codeine were recorded after 2, 4, 8, 24 and 48 h and on days 3-5 postoperatively. After 1 month, patients were interviewed by phone for pain, and analgesic intake after hospital discharge. RESULTS: Morphine consumption (mean +/- SD) was 35 +/- 15.7 mg in the control and 28 +/- 12.1 mg in the gabapentin group (P = 0.21). Median number (range) of paracetamol 500 mg/codeine 30 mg tablets taken during days 3-5 was 1.0 (0-6) in the control and 2.0 (0-9) in the gabapentin group (P = 0.35). The visual analogue scores at rest and after cough did not differ between the two groups (F = 0.92, df = 1, P = 0.34 and F = 0.56, df = 1, P = 0.46, respectively). One month after surgery, 22/27 (81%) of the control group and 9/25 (36%) of the gabapentin group reported pain in the surgical area (chi(2) = 11.15, P = 0.002), while 11/27 (41%) of controls and 7/25 (28%) of gabapentin patients consumed analgesics for pain (chi(2) = 0.93, P = 0.39). The intensity of pain was decreased in the gabapentin group (chi(2) = 12.6, P = 0.003). CONCLUSIONS: Gabapentin has no effect on immediate pain after abdominal hysterectomy but decreases pain 1 month postoperatively.

Painful neuropathy alters the effect of gabapentin on sensory neuron excitability in rats.

BACKGROUND: Pain following peripheral nerve injury is associated with increased excitability of sensory neurons. Gabapentin (GBP), a novel anticonvulsant with an uncertain mechanism of action, is an effective treatment for neuropathic pain. We therefore investigated the effect of GBP on dorsal root ganglion (DRG) neurons from normal rats and those with painful peripheral nerve injury. METHODS: Dorsal root ganglions were excised from rats with neuropathic pain behaviour following chronic constriction injury (CCI) of the sciatic nerve, and from normal rats. Intercellular recordings were made from myelinated sensory neuron somata using a microelectrode technique from DRGs bathed in artificial CSF with or without GBP (100 microM). RESULTS: Compared with normal neurons, injury decreased the refractory interval (RI) for repeat action potential (AP) generation increased the number of APs during sustained depolarization, and shortened the after hyperpolarization following an AP. In normal neurons, GBP decreased the RI and increased the AP number during sustained depolarization. In an opposite fashion, the result of GBP application to injured neurons was a decreased number of APs during depolarization and no change in RI. In injured neurons only, GBP increased the time-to-peak for AP depolarization. CONCLUSIONS: Nerve injury by CCI is associated with increased sensory neuron excitability, associated with a decreased AHP. In normal peripheral sensory neurons, GBP has pro-excitatory effects, whereas GBP decreases excitability in injured neurons, possibly on the basis of altered sodium channel function.

Academic anesthesiologists' views on the importance of the impact factor of scientific journals: a North American and European survey.

PURPOSE: To investigate the views of North American and European anesthesiologists on the value of the impact factor (IF). METHOD: Four hundred thirty-eight anesthesiologists in Canada, the United States of America (USA), and Europe were polled about the importance of the IF regarding hiring, promotions, funding of research and to express their personal views. RESULTS: IF of a candidate's publications is a criterion in 38% of academic appointments in Canada and USA vs 81% in Europe (P <0.0001). The importance of IF to obtain funding is greater in Europe (46%) than in North America (17%) (P <0.0001). Twenty-three percent and 50% of Canadian and American anesthesiologists respectively believe that IF affects financial support (P=0.0389). European anesthesiologists value the IF more than the North Americans (67% vs 31%, P <0.0001). Forty-five percent, 67%, and 56% of the Canadian, American and European anesthesiologists respectively estimate that IF reflects journal quality. Sixty-four percent of anesthesiologists in North America vs 81% in Europe (P=0.0175) pursue to publish in high IF journals. Eighty-six percent, 85% and 90% of the Canadian, American and European anesthesiologists believe that the IF of a journal can be manipulated. Finally, 79%, 67%, and 81% of the Canadian, American, and European anesthesiologists believe that IF should be improved but 33%, 35%, and 30% believe that it should be abandoned. CONCLUSIONS: IF for academic appointments and funding is more important in Europe than in North America. More than 50% of anesthesiologists agree that IF needs to be improved.

Regional block and mexiletine: the effect on pain after cancer breast surgery.

BACKGROUND AND OBJECTIVES: Breast surgery for cancer is associated with chronic pain and sensory abnormalities. The present study investigates the effect of regional block, oral mexiletine, and the combination of both, on acute and chronic pain associated with cancer breast surgery. METHODS: One hundred patients scheduled for cancer breast surgery received either regional block with 18 mL of 1% ropivacaine intraoperatively and oral mexiletine for the first 6 postoperative days (R + M group), or regional block and placebo (R + PL), or normal saline instead of ropivacaine and mexiletine (PL + M), or normal saline and placebo (PL + PL). Postoperative analgesic requirements were recorded daily. Pain was assessed 0, 3, 6, 9, and 24 hours in the postanesthesia care unit (PACU) and on the second to sixth day postoperatively, at rest, and after movement using the visual analog scale (VAS). Three months after surgery, patients were interviewed for the presence and intensity of pain, abnormal sensations, and analgesic requirements. RESULTS: Regional block reduced the number of intramuscular (IM) injections required the first 24 hours (P =.05), the R + PL group requiring less injections versus the PL + M group (P =.037). Lonarid tablet (paracetamol and codeine) consumption from the second to the fifth postoperative day differed among the 4 groups (P =.0304), the R + M group requiring fewer tablets than the PL + PL group (P =.009). Three hours postoperatively, the R + PL group had less pain at rest when compared with all other groups (P <.05 for all comparisons). On the second postoperative day, VAS at rest and after movement was less in the R + M versus the R + PL group (P <.01 and P <.05, respectively). Three months after surgery, the 4 groups were similar with regard to incidence or intensity of pain or analgesic requirements. The R + PL group had a lower incidence (77%) of reduced or absent sensation (P =.016). CONCLUSIONS: Regional block reduced the analgesic requirements in the early postoperative period, while mexiletine combined with regional block reduced the total analgesic requirements during the next 5 postoperative days. Although chronic pain was not affected by these treatments late-abnormal sensation may be diminished by combination of these treatments. Reg Anesth Pain Med 2001;26:223-228.

EMLA reduces acute and chronic pain after breast surgery for cancer.

BACKGROUND AND OBJECTIVES: A significant percentage of women undergoing breast surgery for cancer may develop neuropathic pain in the chest, and/or ipsilateral axilla and/or upper medial arm, with impairment in performing daily occupational activities. We designed this study to determine if the perioperative application of EMLA (eutectic mixture of local anesthetics; AstraZeneca) cream in the breast and axilla area reduces analgesic requirements, as well as the acute and chronic pain after breast surgery. METHODS: Forty-six female patients scheduled for breast surgery received randomly 5 g of EMLA or placebo on the sternal area 5 minutes before surgery, and 15 g on the supraclavicular area and axilla at the end of the operation. Treatment with EMLA cream (20 g) or placebo was also applied daily on the 4 days after surgery. In the postanesthesia care unit (PACU), 3, 6, 9, and 24 hours after surgery, and on the second to sixth day postoperatively, pain was assessed by visual analogue scale (VAS) at rest and after movement, and postoperative analgesic requirements were recorded. Three months later, patients were asked if they had pain in the chest wall, axilla and/or medial upper arm, decreased sensation, if they required analgesics at home, and for the intensity of pain. RESULTS: Acute pain at rest and with movement did not differ between the EMLA and control groups, and the analgesics consumed during the first 24 hours were the same for the EMLA and control groups. However, time to the first analgesia requirement was longer (P = .04), and codeine and paracetamol consumption during the second to fifth days was less (P = .001, and P = .004, respectively) in the EMLA versus the control group. Three months postoperatively, pain in the chest wall, axilla, and the total incidence and the intensity of chronic pain were significantly less in the EMLA versus the control group (P = .004, P = .025, P = .002 and P = .003, respectively). The use of analgesics at home and abnormal sensations did not differ between the 2 groups. CONCLUSIONS: The application of EMLA to patients undergoing breast surgery for cancer reduced the postoperative analgesic requirements and the incidence and intensity of chronic pain.

Painful neuropathy decreases membrane calcium current in mammalian primary afferent neurons.

Hyperexcitability of the primary afferent neuron leads to neuropathic pain following injury to peripheral axons. Changes in calcium channel function of sensory neurons following injury have not been directly examined at the channel level, even though calcium is a primary second messenger-regulating neuronal function. We compared calcium currents (I(Ca)) in 101 acutely isolated dorsal root ganglion neurons from 31 rats with neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve, to cells from 25 rats with normal sensory function following sham surgery. Cells projecting to the sciatic nerve were identified with a fluorescent label applied at the CCI site. Membrane function was determined using patch-clamp techniques in current clamp mode, and in voltage-clamp mode using solutions and conditions designed to isolate I(Ca). Somata of peripheral sensory neurons from hyperalgesic rats demonstrated decreased I(Ca). Peak calcium channel current density was diminished by injury from 3.06+/-0.30 pS/pF to 2. 22+/-0.26 pS/pF in medium neurons, and from 3.93+/-0.38 pS/pF to 2. 99+/-0.40 pS/pF in large neurons. Under these voltage and pharmacologic conditions, medium-sized neuropathic cells lacked obvious T-type calcium currents which were present in 25% of medium-sized cells from control animals. Altered Ca(2+) signalling in injured sensory neurons may contribute to hyperexcitability leading to neuropathic pain.

Airway obstruction due to late-onset angioneurotic edema from angiotensin-converting enzyme inhibition.

PURPOSE: Angioneurotic edema is a well-documented complication of angiotensin-converting enzyme inhibitors (ACEI). We report a case of acute airway obstruction from a late-onset, probable ACEI-related angioneurotic edema and its subsequent management. CLINICAL FEATURES: A 48-yr-old obese man presented for transurethral resection of a bladder tumour (TURBT). His past medical history included hypertension controlled with hydrochlorothiazide and quinapril which had been started 13 mo earlier. Previous surgery was uncomplicated. Midazolam was used for premedication and for intraoperative sedation together with fentanyl and propofol. After uneventful spinal anesthesia with bupivacaine, operation and recovery, he was transferred to the floor. Five hours later he developed severe edema of his face, tongue and neck, with drooling, that progressed into airway obstruction and respiratory arrest. Ventilation was restored via immediate cricothyroidotomy, and a subsequent tracheotomy was completed uneventfully in the operating room. His serum C1 esterase inhibitor levels at 1, 5 and 23 days later were normal. The angioneurotic edema was attributed to the ACEI treatment. The edema resolved after 48 hr, and further follow-up was unremarkable. CONCLUSION: This observation is consistent with other reports that angioneurotic edema from ACEI can occur many months after the initiation of treatment. This can involve the airway and may produce life-threatening respiratory compromise. Physicians should be aware of this association and the possible need for immediate surgical intervention for the establishment of an airway in case of worsening edema or respiratory arrest.