Pain symptoms and pain management options in SARS-CoV-2 environment / Fájdalomtünetek és a fájdalomcsillapítás lehetoségei SARS-CoV-2-környezetben.

Összefoglaló. Az új koronavírusként megismert SARS-CoV-2-fertozés legsúlyosabb szövodményeként a gyulladásos folyamatok jelátvivo molekuláinak elszabadulása - az ún. citokinvihar - kritikus légzési elégtelenséggel társuló akut respirációs diszfunkciós szindrómát vagy többszervi gyulladásos szindrómát okoz. Mostanáig igazolódott, hogy a fertozések legnagyobb részben tünetmentesen vagy enyhe tünetekkel zajlanak. A betegség minden szakaszában elofordulhat enyhe vagy középsúlyos, ritkábban intenzív fájdalom, melyek enyhítésére számos fájdalomcsillapítási lehetoség áll rendelkezésre. A pandémia kezdete óta foglalkoznunk kell a tünetek enyhítésével, akár infektológiai osztályon, akár mutéti ellátás alkalmával. A betegek hazaengedését követoen figyelmet kell fordítanunk az intenzív osztályos ellátás utáni és a COVID-19-et követo tünetek és fájdalmak értékelésére. Idoszeru átfogó összefoglalónkban hangsúlyozzuk a különbözo fájdalomcsillapítók szerepét a COVID-19-fertozéssel összefüggo fájdalommal járó folyamatokban. Orv Hetil. 2021; 162(38): 1511-1519. Summary. As the most severe consequence of the new coronavirus SARS-CoV-2 infection, the cytokine storm - caused by the liberalization of several inflammatory mediators - engenders critical respiratory dysfunction syndrome or multisystem inflammatory syndrome. The most proportion of infections has proven symptomless or with very mild signs of disease so far. Mild, moderate, or rarely intense pain can occur in every phase of the disease, for the treatment of which more than a few analgesic possibilities are readily available. From the start of the pandemic, we have been concerning to ameliorate the symptoms, in either the department of infectology, or operating suites. The post-intensive care pain and post-COVID symptoms should be evaluated and treated after discharge. In this timely and comprehensive article, the role and importance of different analgesics are articulated regarding the COVID-associated painful conditions. Orv Hetil. 2021; 162(38): 1511-1519.

New composite scale for evaluating peripheral nerve block quality in upper limb orthopaedics surgery.

INTRODUCTION: Developments in ultrasound guided (UG) peripheral nerve block (PNB) techniques have significant advantages for patients undergoing trauma surgery. Brachial plexus blockade (BPB) for upper extremity surgery provide superior analgesia, improve recovery and patient satisfaction. To the best of our knowledge there is no tool for evaluation of the quality of UG PNB which concerns the quality of PNB, the tolerance of the patient towards the anaesthetic approach, and postoperative analgesia as well. PATIENTS AND METHODS: Standardized UG BPB anaesthesia - was performed; interscalene-supraclavicular (ISC-SC) and axillary-supraclavicular (AX-SC) approach for upper limb surgery. A GCS like tool was developed with which the Sensory, Motor, Coping of patient and Postoperative (SMCP) pain qualities were measured. The quality of PNBs were evaluated by a quality of anaesthesia graded by anaesthesiologist (QAGA) and the SMCP scale as well, the means of midazolam and opioid consumption during surgery, vital parameters, postoperative pain intensity (VNRS) were compared between the two groups. RESULTS: Ninety three unpremedicated adult patients with ASA I-III were scheduled for unilateral upper limb surgery. Nearly the same mean volumes of local anaesthetic solution were used in the AX-SC and ISC-SC groups (28.3-31.0 ml). There were no significant difference in the quality of PNB measured by QAGA or SMCP scale between the AX-SC and the ISC-SC groups, however 75 patients were assessed as Excellent with the SMCP scale vs. 39 with the QAGA. 97.8% of the patients were in the Excellent and Good category evaluated with SMPC vs. 86% with QAGA (p < 0.001). There was no surgery abandoned due to failed PNB and no tourniquet pain was detected. There was no evidence of side effects or complications of PNB during the follow-up period. DISCUSSION: This composite tool is designed for evaluating the loss of sensory and motor function; the coping of the patient and the postoperative pain as well. Our novel SMCP evaluation tool focuses on the overall condition of the patient during surgery and in the postoperative period. This more precise outcome evaluating scale is significantly superior to the formerly used QAGA in representing the high success rate of UG PNB.

Bipolar hemiarthroplasty for the treatment of femoral neck fractures with minimally invasive anterior approach in elderly.

OBJECTIVES: The purpose of the study was to evaluate the efficacy of hemiarthroplasty with minimally invasive direct anterior approach (DAA) for the treatment of femoral neck fracture in elderly patients. We aimed to compare the DAA and the standard anterolateral approach (ALA), assessing multiple peri­ and post-operative parameters. DESIGN AND SETTING: Between December of 2015 and May of 2017, patients operated with medial femoral neck fractures using bipolar hemiarthroplasty with DAA or ALA were evaluated. The volume of bleeding and transfusion, postoperative level of pain, mobilisation and functional outcome were assessed retrospectively. PARTICIPANTS: Patients between the age of 75 and 85, suffering Garden Type III Pauwels Type III and Garden Type IV medial femoral neck fractures were entered to the study. Patients had no history of anticoagulant therapy; the operation was performed in the first 48 h. All patients received similar postoperative pain management and physiotherapy. The type of implants was determined by the patients' bone morphology and quality. MAIN OUTCOME MEASURES: The outcomes of interest were the level of postoperative pain, blood loss, rate of recovery and physiotherapy, altered gait pattern and accuracy of leg length, related to DAA and ALA techniques. RESULTS: The 51 patients operated with DAA showed significantly less pain, based on VAS (visual analogue scale), starting of the first postoperative day. Those patients who were subjected to DAA met with the criteria of hospital discharge 1.68 days earlier, compared to ALA patients. The length of leg was accurately set in 21% of ALA vs 54.9% of DAA patients. On the 12th week follow-up, limping was detected only 5.9% of DAA vs 46% of ALA groups. On the postoperative 2nd and 6th weeks, the HHS (Harris Hip Score) was significantly better in patients with DAA, compared to ALA (77 vs 65 and 91 vs 77, p < .05). CONCLUSION: The bipolar hemiarthroplasty with DAA allows earlier mobilisation, reduced postoperative pain and need for rehabilitation with an overall better functional outcome, compared to ALA. DAA is proven a reliable choice for femoral neck fractures, offering good outcome and faster recovery, similarly to total hip arthroplasties with degenerative arthritis.

Onset times and duration of analgesic effect of various concentrations of local anesthetic solutions in standardized volume used for brachial plexus blocks.

Visualization of the nerve structures of brachial plexus allows anesthesiologists to use a lower dose of local anesthetics. The content of this low dose is not unequivocal, consequently, the pharmacokinetics of local anesthetics used by various authors are difficult to compare. In this study, the onset times and duration of the analgesic effect of local anesthetic mixture solutions used for brachial plexus blocks are investigated and the quality of anesthesia is compared. 85 unpremedicated American Society of Anesthesiologist physical status I-III, 19-83-year-old patients scheduled for upper limb trauma surgery are assigned to four groups for the axillary-supraclavicular block with lidocaine 1% and bupivacaine 0,5% 1:1 mixture (Group LB) or bupivacaine 0.33% (Group BS) or lidocaine 0,66% (Group LS) or bupivacaine 0.5% and lidocaine 1% 2:1 mixture (Group BL). 0.4 ml/kg was administered to the four groups. The onset time was significantly shorter in the lidocaine group (LS 13.0 ± 1.02) than in the other study groups (LB 16.64 ± 0.89; BS 17.21 ± 0.74; BL 16.92 ± 0.51 min ±SEM, p = 0.002). No differences were observed in the onset times between LB, BS, and BL groups (p > 0.05). Statistical differences were found in the duration of local anesthetics between LB (392.9 ± 20.4), BS (546.4 ± 14.9), LS (172.85 ± 7.8), and BL (458.7 ± 11.9 min ±SEM, p = 0.001). Lidocaine does not shorten the onset times, but significantly decreases the duration of action of bupivacaine when used in mixture solutions. Lidocaine exhibits a good quality of block in the applied dose, while other solutions have excellent quality. Bupivacaine without lidocaine has the longest duration of action to achieve the longest postoperative analgesia.

The first experiences with the palliative tumor board discussions in the University of Pécs / Az elso tapasztalatok a palliatív onkoteamrendszer muködésével kapcsolatban a Pécsi Tudományegyetemen.

INTRODUCTION: Palliative, symptomatic and end-of-life care of advanced and metastatic cancer patients is a great challenge for every health care system. With the initiation and establishment of the multidisciplinary palliative tumor board (MPTB), our aims were the timely referral of patients to palliative care, and the avoidance of multiple unnecessary emergency visits and over-diagnostics without further treatment consequences. METHOD AND RESULTS: The MPTB meetings were held biweekly. The core members of the team were: palliative care consultant, medical oncologist, internal medicine physician, psychologist, psychiatrist, and oncology and palliative medicine nurses. From May 2019 till January 2020, we discussed the medical history of 97 cases of 93 cancer patients with advanced disease states; in one meeting the team usually discussed over 6-10 complex patient histories. In every case we determined the actual form of the necessary palliative care, e.g., outpatient clinic, home care, or institutional referral, and we decided on further possible and realistic oncology treatment regimes. A few months after the introduction of the new MPTB, we detected a decrease of the unnecessary emergency unit referrals considering the patients whose histories were discussed. CONCLUSIONS: Although the initial MPTB discussions had an intense emotional tone, they shortly became thoughtful and operational expert meetings. We believe that the MPTB system fully promotes the early and timely access of advanced cancer patients to appropriate palliative care and facilitates gradual changes in the medical oncologists' approach from the absolute curative determination to a supportive medical attitude. Orv Hetil. 2020; 161(34): 1423-1430.

[Ultrasound imaging has a potential to exhibit biotechnical advance in perioperative pain management]. / Az ultrahang-képalkotás alkalmazása biotechnikai elorelépés a perioperatív fájdalomcsillapításban.

The perioperative pain management - instead of the efforts, guidelines and protocols - is underestimated and undertreated. Even in the case of general anaesthesia, the nervous system is overwhelmed by copious quantities of nociceptive stimuli at surgical incision. Stress and pain-modulation processes are triggered which can have significant influence on the outcome. Often the pain-management is discontinued, so a notable part of patients complain about pain in the ward after surgery. Regional anaesthesia conceptually prevents noxious inputs to enter the central nervous system, beyond surgical anaesthesia it is pertinent to achieve excellent analgesia in the immediate postoperative period as well. Based on current literature, this paper provides an overview of the history and role of regional anaesthesia in the multidimensional model of pain. Besides the sensitization caused by nociceptive stimuli - peripheral and central sensitization, descending modulation - there are several biopsychosocial factors involved in pain pathophysiology. Preventing the side effects of general anaesthesia, the ultrasound-guided peripheral nerve blockade is a safe technique with high success rate, rare side effects, achieving long-lasting, excellent analgesia. Continuous perineural catheter placed under ultrasound provides extended pain control. As a part of multimodal analgesia, peripheral nerve blockade prevents central sensitization. After surgery, the pain intensity of patients under peripheral nerve blockade is less, the chronification tendency is decreased, the quality of life and patients' comfort are improved, and the stress-response is attenuated. The greater part of patients are protected from the undesirable side effects of general anaesthesia. Nowadays, it is an unequivocal evidence that the increasingly used peripheral nerve blockades prior to incision are efficient tools in the prevention of chronic postoperative pain. Ultrasound guidance is suitable not only for surgical anaesthesia, but for postoperative pain management as well, however, besides economic factors, the main goal of this technique is to match the best interest of the patients. Orv Hetil. 2019; 160(15): 573-584.

Actions of 3-methyl-N-oleoyldopamine, 4-methyl-N-oleoyldopamine and N-oleoylethanolamide on the rat TRPV1 receptor in vitro and in vivo.

N-oleoyldopamine (OLDA) has been identified as an agonist of the transient receptor potential vanilloid type 1 (TRPV1) receptor. A related fatty acid amide, N-oleoylethanolamide (OEA), was found to excite sensory neurons and produce visceral hyperalgesia via activation of the TRPV1 receptor, however, a recent study described this agent as an antinociceptive one. The aim of the present paper was to characterize two newly synthesized derivatives of N-oleoyldopamine, 3-methyl-N-oleoyldopamine (3-MOLDA) and 4-methyl-N-oleoyldopamine (4-MOLDA) as well as OEA with regard to their effects on the TRPV1 receptor. Radioactive 45Ca2+ uptake was measured in HT5-1 cells transfected with the rat TRPV1 receptor and intracellular Ca2+ concentration was monitored by fura-2 microfluorimetry in cultured trigeminal sensory neurons. Thermonociception was assessed by determining the behavioral noxious heat threshold in rats. 3-MOLDA induced 45Ca2+ uptake in a concentration-dependent manner, whereas 4-MOLDA and OEA were without effect. 4-MOLDA and OEA, however, concentration-dependently reduced the 45Ca2+ uptake-inducing effect of capsaicin. In trigeminal sensory neurons, 3-MOLDA caused an increase in intracellular Ca2+ concentration and this effect exhibited tachyphylaxis upon repeated application. Again, 4-MOLDA and OEA failed to alter intracellular Ca2+ levels. Upon intraplantar injection, 3-MOLDA caused an 8-10 degrees C drop of the noxious heat threshold in rats which was inhibited by the TRPV1 receptor antagonist iodo-resiniferatoxin. 4-MOLDA and OEA failed to alter the heat threshold but inhibited the threshold drop induced by the TRPV1 receptor agonist resiniferatoxin. These data show that 3-MOLDA behaves as an agonist, whereas 4-MOLDA and OEA appear to be antagonists, at the rat TRPV1 receptor.

Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice.

Capsaicin-sensitive, TRPV1 (transient receptor potential vanilloid 1) receptor-expressing primary sensory neurons exert local and systemic efferent effects besides the classical afferent function. The TRPV1 receptor is considered a molecular integrator of various physico-chemical noxious stimuli. In the present study its role was analysed in acute nociceptive tests and chronic neuropathy models by comparison of wild-type (WT) and TRPV1 knockout (KO) mice. The formalin-induced acute nocifensive behaviour, carrageenan-evoked inflammatory mechanical hyperalgesia and partial sciatic nerve lesion-induced neuropathic mechanical hyperalgesia were not different in WT and KO animals. Acute nocifensive behaviour after intraplantar injection of phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), was absent in TRPV1 KO animals showing that PKC activation elicits nociception exclusively through TRPV1 receptor sensitization/activation. Thermal hyperalgesia (drop of noxious heat threshold) and mechanical hyperalgesia induced by a mild heat injury (51 degrees C, 15s) was smaller in KO mice suggesting a pronociceptive role for TRPV1 receptor in burn injury. Chronic mechanical hyperalgesia evoked by streptozotocin-induced diabetic and cisplatin-evoked toxic polyneuropathy occurred earlier and were greater in the TRPV1 KO group. In both polyneuropathy models, at time points when maximal difference in mechanical hyperalgesia between the two groups was measured, plasma somatostatin concentrations determined by radioimmunoassay significantly increased in WT but not in TRPV1 KO mice. It is concluded that sensitization/activation of the TRPV1 receptor plays a pronociceptive role in certain models of acute tissue injury but under chronic polyneuropathic conditions it can initiate antinociceptive counter-regulatory mechanisms possibly mediated by somatostatin released from sensory neurons.

Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics.

1. An increasing-temperature hot plate (ITHP) was introduced to measure the noxious heat threshold (45.3+/-0.3 degrees C) of unrestrained rats, which was reproducible upon repeated determinations at intervals of 5 or 30 min or 1 day. 2. Morphine, diclofenac and paracetamol caused an elevation of the noxious heat threshold following i.p. pretreatment, the minimum effective doses being 3, 10 and 200 mg kg(-1), respectively. 3. Unilateral intraplantar injection of the VR1 receptor agonist resiniferatoxin (RTX, 0.048 nmol) induced a profound drop of heat threshold to the innocuous range with a maximal effect (8-10 degrees C drop) 5 min after RTX administration. This heat allodynia was inhibited by pretreatment with morphine, diclofenac and paracetamol, the minimum effective doses being 1, 1 and 100 mg kg(-1) i.p., respectively. 4. The long-term sensory desensitizing effect of RTX was examined by bilateral intraplantar injection (0.048 nmol per paw) which produced, after an initial threshold drop, an elevation (up to 2.9+/-0.5 degrees C) of heat threshold lasting for 5 days. 5. The VR1 receptor antagonist iodo-resiniferatoxin (I-RTX, 0.05 nmol intraplantarly) inhibited by 51% the heat threshold-lowering effect of intraplantar RTX but not alpha,beta-methylene-ATP (0.3 micromol per paw). I-RTX (0.1 or 1 nmol per paw) failed to alter the heat threshold either acutely (5-60 min) or on the long-term (5 days). The heat threshold of VR1 receptor knockout mice was not different from that of wild-type animals (45.6+/-0.5 vs 45.2+/-0.4 degrees C). 6. In conclusion, the RTX-induced drop of heat threshold measured by the ITHP is a novel heat allodynia model exhibiting a high sensitivity to analgesics.

Analgesic effect of TT-232, a heptapeptide somatostatin analogue, in acute pain models of the rat and the mouse and in streptozotocin-induced diabetic mechanical allodynia.

Somatostatin released from capsaicin-sensitive sensory nerves exerts systemic anti-inflammatory and antinociceptive actions. TT-232 is a stable, peripherally acting heptapeptide (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2) somatostatin analogue with highest binding affinity for somatostatin sst4 receptors. It has been shown to inhibit acute and chronic inflammatory responses and sensory neuropeptide release from capsaicin-sensitive nociceptors. In the present study the antinociceptive effects of TT-232 were analysed using both acute and chronic models of nociception. Formalin-induced pain behaviour, noxious heat threshold and streptozotocin-induced diabetic neuropathic mechanical allodynia were examined in rats and phenylquinone-evoked abdominal constrictions were tested in mice. TT-232 (80 microg/kg i.p.) inhibited both early (0-5 min) and late phases (25-45 min) of formalin-induced nociception as revealed by determination of the composite pain score. The minimum effective dose to elevate the noxious heat threshold and diminish the heat threshold drop (heat allodynia) evoked by resiniferatoxin (0.05 nmol intraplantarly) was 20 and 10 microg/kg i.p., respectively, as measured by an increasing-temperature hot plate. TT-232 (10-200 microg/kg s.c.) significantly inhibited phenylquinone-evoked writhing movements in mice, but within this dose range no clear dose-response correlation was found. Five weeks after streptozotocin administration (50 mg/kg i.v.) the diabetes-induced decrease in the mechanonociceptive threshold was inhibited by 10-100 microg/kg i.p. TT-232. These findings show that TT-232 potently inhibits acute chemical somatic/visceral and thermal nociception and diminishes chronic mechanical allodynia associated with diabetic neuropathy, thereby it could open new perspectives in the treatment of various pain syndromes.