Prolonged Pain Research Articles

Nitinol stents placed in iliac veins are not associated with prolonged back pain.

Endovascular stenting is the standard of care for the management of symptomatic chronic venous obstruction. The increased radial resistive force and longer lengths of Nitinol stents have led to questions over persistent post-operative back pain. The purpose of this investigation was to assess the incidence and severity of post-operative back pain of Nitinol stents compared to Wallstents. A retrospective review of data at the Center for Vascular Medicine was performed. Patient demographics, pre-operative, oneweek, three-, six,- and 12month visual analog pain scores (VAS) for back pain, stent type, diameter, length, and vein locations were assessed. From April 2014 to November 2021, 627 (412 women/215 men) patients were assessed for the presence of post-operative back pain after an initial iliac vein stent placement. Stents utilized were Wallstents (n = 114), Venovo (n = 342), and Abre (n = 171). The most common Nitinol stent diameter and lengths were 14mm, 16mm, and 120mm, respectively (p ≤ .03). The incidence of back pain at oneweek was 66% (411/627). VAS scores at oneweek and one, three, and sixmonths post-operatively were the following: Wallstents-2.6 ± 3 (n = 66), 1.7 ± 2.6 (n = 43) 0.7 ± 2 (n = 51), and 0 ± 0 (n = 27); Abre-3.5 ± 3 (n = 130), 3.8 ± 3 (n = 19), 1.2 ± 2.5 (n = 12), and 1 ± 2 (n = 5); and Venovo- 2.5 ± 3 (n = 216), 2.4 ± 3 (n = 70), 0.9 ± 2 (n = 68), and 0.6 ± 1.7 (n = 49). There was no difference in the severity of back pain at any time point (p ≥ .99). The development of back pain was unrelated to stent type, diameter, length, or covered vein territory. Post-operative back pain was observed in 66% of patients at oneweek. The average pain score at oneweek for the entire cohort was three, which declined to less than one at onemonth. No difference in the severity of back pain between groups was observed at any time point, and the development of back pain is unrelated to stent type, diameter, length, or covered vein territory.

Post-COVID-19 Menstrual Symptom Disorders Relating to Anxiety and Long COVID-19 Symptoms

Objectives: Coronavirus disease 2019 (COVID-19) can affect the menstrual cycle and menstrual flow. To examine changes in menstrual symptoms of women recovering from COVID-19 and to identify factors that influence these changes. Materials and Methods: A questionnaire, prepared using Google Forms, was completed by 180 women (26.08±6.62 years) recovered from COVID-19. The menstrual symptoms, menstrual pain, fatigue severity and anxiety level of the participants were evaluated respectively with the Menstrual Symptom Questionnaire (MSQ), visual analogue scale (VAS), fatigue severity scale (FSS), and coronavirus anxiety scale (CAS). Results: Post-COVID-19 individuals’ MSQ totals, subgroup scores, FSS scores and menstrual pain levels showed significant increase compared to pre-COVID-19. Regression analysis identified that age at menarche, changes in FSS and VAS scores as contributors to 38.4% of the variance explained in the significant regression for change in MSQ score. Individuals with prolonged fatigue, muscle– joint pain and dyspnea symptoms showed increase in MSQ total scores (P=0.006, P=0.009, P=0.046 respectively) and MSQ negative effects/somatic complaints scores (P=0.004, P=0.002, P=0.017 respectively). Individuals with prolonged gastrointestinal symptoms showed increase in MSQ pain symptoms (P=0.029) and MSQ coping methods scores (P=0.002), while those with prolonged muscle and joint pain showed increase in MSQ coping methods (P=0.022) scores. Conclusions: The results of this study indicated that menstrual symptoms, fatigue, and menstrual pain severity are deteriorated in women recovered from COVID-19. Age at menarche, changes in fatigue and menstrual pain after COVID-19 were determiners of the deteriorated menstrual symptoms. Menstrual symptoms were more severe in those who have prolonged fatigue, dyspnea, muscle– joint pain and gastrointestinal symptoms.

ODP080 Bisphosphonate treatment for osteoporosis in children with Gorham-Stout syndrome: a case report

Abstract Background Gorham-Stout disease (GSD) is a rare disease defined by progressive bone disappearance due to massive unicentric or multicentric osteolysis with proliferation of vascular structures. Symptoms and signs vary depending on the site of invasion. Including some self-limiting GSD, most treatments are palliative and limited to symptom management. Various treatments have been tried for GSD, but there are no standardized treatment protocols. Treatment includes radiological treatment, surgery, and medications such as bone absorption inhibitors (calcitonin, bisphosphonate (BP)), vitamin D and immune modulators (interferon alpha-2b, Sirolimus) Case presentation: A 4-year-old female patient presented with prolonged back pain after a fall. Pathologic compression fracture in T9, L1 vertebrae identified in simple spine image, and GSD was confirmed by MRI and biopsy finding as hemangioma in vertebrae. This patient has been treated with a combination therapy of Sirolimus and BP for 1 year. BP treatment consist with oral BP (Alendronate) between 3 intravenous BP (Pamidronate) every 4 months. After a year of treatment, BMD improved from initial -1.3 TBLH (z-score) to -0.5/0.4/0.6 Spine/Both femur (z-score), but MRI findings suggest mild aggravation of multiple compression fractures of spines of T9-L5. After 1-year of treatment, at present, the girl is alive and staying with tolerable condition. Conclusions Combination treatment with bisphosphonate and Sirolimus for childhood GSD can be helpful in slowing the demineralization of GSD without any significant adverse effect. Presentation: No date and time listed

Pseudomeniscus after knee arthroplasty: A case series for arthroscopic management of this problem and systematic review of literature

IntroductionMost patients undergoing total knee arthroplasty (TKA) experience favorable outcomes. Some patients, however, experience prolonged post-operative knee pain and tenderness at the joint line. This has been attributed in some cases to soft tissue impingement due to pseudomeniscus. The purpose of this study is to evaluate patient outcomes for arthroscopic excision of pseudomeniscus for persistent knee pain after TKA and to perform a review of literature for pseudomeniscus after knee arthroplasty. MethodsA retrospective analysis of patients undergoing arthroscopy to remove soft tissue causing persistent knee pain after previous TKA was performed. Outcome scores were asked at three time points: prior to knee arthroplasty, prior to arthroscopy, and post-arthroscopy at final follow-up. Subjective satisfaction with surgery and willingness to repeat procedures were also recorded. A two-tailed distribution paired t-test was used to determine statistical significance (p < 0.05). We also performed a review of the literature for pseudomeniscus complications for comparison. ResultsNine out of eleven patients were considered eligible to be assessed for post-operative satisfaction. Seven out of nine patients reported complete satisfaction and eight participants stated they would undergo the procedures again if they have to. Among 9 included patients, five patients have successfully completed the clinical score evaluation survey. The mean age of the patients with clinical score evaluation at the time of TKA was 61 years (range, 53–72) and the time between TKA and undergoing arthroscopy was 8 months (range, 5–13). The average follow-up period for patient-determined assessment after the arthroscopic procedure was 71 months (range, 16–115). All 5 patients reported improved Oxford Knee Scores (p=0.017), Western Ontario and McMaster Universities Osteoarthritis Index (p=0.023), and pain scores (p=0.018) comparing pre-arthroscopy to post-arthroscopy at follow-up. ConclusionArthroscopic removal of pseudomeniscus after TKA provides promising results in patients who experience persistent knee joint line pain and tenderness. Considering our results and review of literature, we recommend including pseudomeniscus in the differential for post arthroplasty knee pain. Study designCase series with a review of literature.

Twelve-Month Results from a Prospective Clinical Study Evaluating the Efficacy and Safety of Cellular Bone Allograft in Subjects Undergoing Lumbar Spinal Fusion.

While autologous bone grafts remain the gold standard for spinal fusion procedures, harvesting autologous bone is associated with significant complications, including donor site infection, hematomas, increased operative time, and prolonged pain. Cellular bone allograft (CBA) presents an alternative to autologous bone harvesting, with a favorable efficacy and safety profile. The current study further investigates CBA as an adjunct to lumbar spinal fusion procedures. A prospective, multicenter, open-label clinical study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT02969616). Radiographic fusion status was assessed by an independent review of dynamic radiographs and CT scans. Clinical outcome measures included the Oswestry Disability Index (ODI) and visual analogue scale (VAS) for back and leg pain. Adverse-event reporting was conducted throughout 12 months of follow-up. Available subject data at 12 months were analyzed. A total of 274 subjects were enrolled into the study, with available data from 201 subjects (73.3%) who completed 12 months of postoperative radiographic and clinical evaluation at the time of analysis. Subjects had a mean age of 60.2 ± 11.5 years. A higher number of women (n = 124, 61.7%) than men (n = 77, 38.3%) were enrolled, with a collective mean BMI of 30.6 + 6.5 kg/m² (range 18.0-51.4). At month 12, successful fusion was achieved in 90.5% of subjects. A significant (<i>p</i> &amp;lt; 0.001) improvement in ODI, VAS-back, and VAS-leg clinical outcomes was also observed compared to baseline scores. One adverse event related to CBA (postoperative radiculopathy) was reported, with surgical exploration demonstrating interbody extrusion of graft material. This subject reported successful fusion at month 12. CBA represents a viable substitute for harvesting of autograft alone with a high rate of successful fusion and significant improvements in subject-reported outcomes, such as pain and disability. Positive benefit was observed in subjects reporting single and multiple risk factors for pseudoarthrosis.

This Month in Anesthesiology

This Month in Anesthesiology

Headache Disorders: Does Pain Affect Blood Pressure?

The perspective that pain corresponds to elevated blood pressure is overly simplistic. Our objective is to investigate and debunk misconceptions regarding the effect of pain on blood pressure. While pain can increase blood pressure in the acute setting, prolonged pain and migraine's effect on blood pressure varies and can result in lower-than-expected blood pressure. Therefore, attributing pain as a sole source of elevation of blood pressure may lead to delays in diagnosing hypertension. Based on limited studies available, comorbid pain and chronic hypertension have a higher concurrence than in the general population. We will review current literature to investigate the effect of pain on blood pressure and prevalence of hypertension in chronic pain sufferers. A better understanding of pain's effect on blood pressure will help practitioners appropriately diagnose and counsel patients without disproportionately attributing high blood pressure to pain.

P-022 USE OF SEPRAFILM ADHESION BARRIER® IN COMPLEX LARGE INCISIONAL HERNIA

Abstract Aim The short-term results of the use of seprafilm® as a reinforcement of the peritoneum are presented. Material and Methods Seprafilm® was used in 5 patients with large midline and lateral incisional hernia in which Transversus Abdominis Release Technique was performed in which it was necessary to explant mesh previously. This weakness of the peritoneum was reinforced with the seprafilm® plates, to isolate the intra-abdominal contents from the mesh. Results The patients treated had an average stay of 6.6 days. All of them carried drains. There were no infectious complications in surgical site. There were no prolonged pain. All of them began tolerance the day after the surgery. At one month of the surgical intervention, there were no signs of infection, seroma or higher pain than 3 on the EVA scale. Discussion Post-operative adhesions to mesh are related to intestinal fistulas. The use of preperitoneal space to place the mesh is a good option, although sometimes it can have continuity problems, especially when there are explants of previous materials. The use of barrier materials is appropriate in these cases. Conclusion The use of Seprafilm® can be a good option as a barrier between viscera and prostheses for the prevention of adhesions.

Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis.

Substantial advances in biotherapeutics are distinctly lacking for musculoskeletal diseases. Musculoskeletal diseases are biomechanically complex and localized, highlighting the need for novel therapies capable of addressing these issues. All frontline treatment options for arthrofibrosis, a debilitating musculoskeletal disease, fail to treat the disease etiology-the accumulation of fibrotic tissue within the joint space. For millions of patients each year, the lack of modern and effective treatment options necessitates surgery in an attempt to regain joint range of motion (ROM) and escape prolonged pain. Human relaxin-2 (RLX), an endogenous peptide hormone with antifibrotic and antifibrogenic activity, is a promising biotherapeutic candidate for musculoskeletal fibrosis. However, RLX has previously faltered through multiple clinical programs because of pharmacokinetic barriers. Here, we describe the design and in vitro characterization of a tailored drug delivery system for the sustained release of RLX. Drug-loaded, polymeric microparticles released RLX over a multiweek time frame without altering peptide structure or bioactivity. In vivo, intraarticular administration of microparticles in rats resulted in prolonged, localized concentrations of RLX with reduced systemic drug exposure. Furthermore, a single injection of RLX-loaded microparticles restored joint ROM and architecture in an atraumatic rat model of arthrofibrosis with clinically derived end points. Finally, confirmation of RLX receptor expression, RXFP1, in multiple human tissues relevant to arthrofibrosis suggests the clinical translational potential of RLX when administered in a sustained and targeted manner.

Duelo egótico por el cuerpo doliente. Estudio fenomenológico y psicoanalítico del dolor intenso

The experience of an intense and prolonged physical pain reported by Rafael Argullol in his book "Davalú or pain" promotes a phenomenological and psychoanalytic analysis of mourning (combat) and mourning (elaboration within the self) due to loss of health, strength and autonomy. Pain is the cry of the body that remains in a prementalizing and meaningless space which challenges the environment but it remains outside of subjectivity and it breaks the link with the others, especially when it is located only in the body and it does not include the person as intentional being. From its radical corporeality, the pain closes to (corners) the self, it annihilates the previous identity and it reveals our maximum vulnerability and defenselessness. From the egotic retreat to a narcissism without language, the self plunges into a self-mourning that only ends when the pain stops. There is no pact with the suffering body’s ache, especially if it cannot be transformed into suffering

Post-COVID-19 pain syndrome: a descriptive study in Turkish population.

BackgroundThe new type of corona virus has a wide range of symptoms. Some people who have COVID-19 can experience long-term effects from their infection, known as post-COVID conditions. The authors aimed to investigate prolonged musculoskeletal pain as a symptom of the post-COVID-19 condition.MethodsThis is a descriptive study on the patients who were diagnosed with COVID-19 in a university hospital, between March 2020 and March 2021. Patient records and an extensive questionnaire were used to obtain relevant demographic and clinical characteristics, including hospitalization history, comorbidities, smoking history, duration of the pain, the area of pain, and the presence of accompanying neuropathic symptoms.ResultsOf the diagnosed patients, 501 agreed to participate in the study. Among the participants, 318 had musculoskeletal pain during COVID-19 infection, and 69 of them reported prolonged pain symptoms as part of their a post-COVID condition which could not be attributed to any other cause. The mean duration of pain was 4.38 ± 1.73 months, and the mean pain level was 7.2 ± 4.3. Neuropathic pain symptoms such as burning sensation (n = 16, 23.2%), numbness (n = 15, 21.7%), tingling (n = 10, 14.5%), stinging (n = 4, 5.8%), freezing (n = 1, 1.4%) were accompanied in patients with prolonged musculoskeletal pain.ConclusionsPatients with COVID-19 may develop prolonged musculoskeletal pain. In some patients, neuropathic pain accompanies it. Awareness of prolonged post-COVID-19 pain is crucial for its early detection and management.

Efficacy of peritonsillar infiltration of levobupivacaine-dexamethasone versus levobupivacaine-dexmedetomidine in children undergoing tonsillectomy surgery

Purpose We evaluated the quality of analgesia produced by peritonsillar infiltration of levobupivacaine with either dexamethasone or dexmedetomidine in children undergoing tonsillectomy surgery. Patients and methods Patients scheduled for tonsillectomy were randomly allocated into three groups with 27 patients in each group. Group L received peritonsillar infiltration of 5 ml in volume of 0.4 mg/kg of 0.5% levobupivacaine, while group D received peritonsillar infiltration of 5 ml in volume of 0.4 mg/kg of 0.5% levobupivacaine mixed with dexamethasone 0.5 mg/kg and group X received peritonsillar infiltration of 5 ml in volume of 0.4 mg/kg of 0.5% levobupivacaine mixed with dexmedetomidine 1 μg/kg (with infiltration of 2.5 ml in each tonsil in all groups) with the first postoperative analgesic request as the primary outcome. Results Postoperative time to first analgesic paracetamol request was prolonged in group D (19.51±2.34 h) compared with group L (4.15±0.53 h) and group X (15.74±2.29 h). Face, leg, activity, cry, consolability (FLACC) Behavioral Pain Assessment score at rest and during swallowing decreased in group D compared with group L and group X. Total postoperative analgesic consumption decreased in group D (581.48±165.7 mg) compared with group L (1303.51±90.10 mg) and group X (680.50±160.67 mg). Conclusions We concluded that peritonsillar infiltration of levobupivacaine when mixed with either dexamethasone or dexmedetomidine for patients undergoing tonsillectomy produced prolonged analgesia; however, dexamethasone was superior to dexmedetomidine with more prolonged time to first paracetamol request and prolonged late postoperative pain relief.

Postoperative Pain in Outpatient Orthopedic Foot and Ankle Trauma Surgery Patients

Category: Trauma Introduction/Purpose: Opioid pain medications are frequently prescribed after orthopedic surgery as effective tools for pain relief, but with adverse consequences such as addiction and overdose. Postoperative pain control can vary depending on patient opioid prescription history and pain expectations. There are limited studies regarding pain and anxiety levels following orthopedic foot and ankle trauma surgery, with a lack of formal guidelines in prescribing opioid medications to this patient population. The overall purpose of this study was to gain an understanding of postoperative pain and anxiety in patients undergoing outpatient foot and ankle trauma surgery. This study additionally sought to identify any risk factors that may predispose a patient to increased postoperative pain and anxiety, resulting in a potentially increased pain medication requirement. Methods: A subanalysis of 50 patients from a prospective, observational study was performed, examining adult patients undergoing outpatient foot and ankle trauma surgery performed by trauma fellowship-trained senior investigators. Patients were enrolled and given pertinent reference materials including access to an automated texting survey platform to collect data regarding their postoperative pain, anxiety, and opioid medication use. Patients were stratified by procedure type (irrigation &amp; debridement/hardware removal, foot/syndesmosis ORIF, ankle ORIF, pilon ORIF) and by receiving perioperative regional anesthetic block versus local anesthetic. Pain and anxiety were measured with the Numeric Rating Scale for Pain (scale of 1-10) and the Visual Facial Anxiety Scale (scale of 1-5), respectively. The primary outcome measured was the number of days on average for a patient to discontinue opioid medication. Secondary endpoints consisted of pain level &lt; 4, anxiety level &lt; 2, patient-specific and surgery-related factors that may affect these variables. Results: Postoperatively, it took an average of 9.6 days until opioids were discontinued, 8.2 days for pain to subside below 4, and 6.6 days until anxiety reduced under 2. Foot/syndesmosis ORIF and older age were associated with prolonged pain medication use (p&lt;0.05). Drug use and older age limited the chance of obtaining a pain score under 4 (p&lt;0.05). Psychiatric history and older age decreased the odds of obtaining an anxiety score under 2 (p&lt;0.05). White race improved the chance of obtaining an anxiety score under 2 and tapering off pain medications (p&lt;0.05). When stratified by procedure type or analgesic adjuvants (regional block vs local), there were no significant differences in pain and anxiety scores. Conclusion: Our study shows that regardless of procedure type or analgesic adjuvant used, it takes approximately eight days for postoperative pain levels to decrease to 4 out of 10 and six days for anxiety levels to decrease to 2 out of 5, with patients requiring opioid pain medications for an average of 10 days. Risk factors such as older age, prior drug use, and psychiatric history increased postoperative pain, anxiety, and use of opioid pain medications. This data may be utilized by orthopedic surgeons in providing safe, effective, and evidence-based pain management prescribing practices in anticipating postoperative pain and anxiety.

Применение маннитол термостабилизированных ГК-комплексов в лечении гонартроза

INTRODUCTION: Hyaluronic acid (HA) is a natural glycosaminoglycan which is an integral component of both the matrix of articular cartilage and synovial fluid with its unique rheological properties that are lost in gonarthrosis, which leads to a decrease of viscoelastic characteristics of the synovia and destruction of the cartilage. AIM: To evaluate the effectiveness and safety of the use of Hyapro sterile biopolymer synovial fluid prosthesis in a disposable syringe for intra-articular injection at a concentration of 1.5% — 2 ml in treatment of gonarthrosis. MATERIALS AND METHODS: From September 2020 to April 2022 at settings of the orthopedic department of Ryazan Regional Clinical Hospital, an open prospective non-comparative study of the effectiveness and safety of Hyapro sterile biopolymer synovial fluid prosthesis at a concentration of 1.5% — 2 ml in 30 patients with 2 to 3 stage gonarthrosis according to Kellgren–Lawrence scale was carried out. Prior to the treatment, and also 3 and 6 months after, the severity of clinical symptoms on VAS, WOMAC, Leken scales, the quality of life according to SF-36 questionnaire were registered; the biochemical markers namely cartilaginous oligomatrix peptide (COMP), metal matrix proteinase 3 (MMR 3) were determined with the use of StatFax enzyme-linked plate analyzer (Awareness Technology, USA). RESULTS: In general, the studied drug was well tolerated by patients: there were no typical for intra-articular injections cases of clinically important adverse reactions like prolonged pain at the injection site, expansion-like sensation, an elevation of local temperature, and changes in the color of skin or changes of the shape of the knee joint. Just transient local tenderness in 6.7% of injection cases was noted. We revealed a statistically significant decrease in serum MMR-3 levels by 6 months of follow-up, which reflects a reduction of the inflammatory component in osteoarthritis of the joint studied. Besides, a gradual increase in COMP levels by the 6th month of the study was found, which may be an evidence of activation of the protein after the course of treatment to replenish the cartilage matrix. The results on VAS, WOMAC scales, and Leken algofunctional index demonstrated similar positive dynamics: a statistically reliable decrease in such parameters as pain, stiffness, and impaired functioning by the 3rd month of follow-up compared with the initial level; this trend was remaining in 6 months. After 3 months of treatment, there was a reliable improvement of the quality of life on the subscale of the physical component of health compared with the initial level, which persisted until the end of the study. On the subscale of the psychological component of health, no changes were found during the period. CONCLUSION: The course use of Hyapro biopolymer synovial fluid prosthesis on the basis of hyaluronic acid thermally stabilized with mannitol, in symptomatic gonarthrosis of intermediate stages, permits safely and effectively reduce pain and the inflammatory response, improve the function of the affected joint through restoration of viscoelastic and protective properties of synovial fluid for up to at least 6 months, improving the quality of life of patients.

Multifocal tDCS Targeting the Motor Network Modulates Event-Related Cortical Responses During Prolonged Pain

Multifocal transcranial direct current stimulation (tDCS) targeting several brain regions is promising for inducing cortical plasticity. It remains unknown whether multifocal tDCS aimed at the resting-state motor network (network-tDCS) can revert N2-P2 cortical responses otherwise attenuated during prolonged experimental pain. Thirty-eight healthy subjects participated in 2 sessions separated by 24 hours (Day1, Day2) of active (n = 19) or sham (n = 19) network-tDCS. Experimental pain induced by topical capsaicin was maintained for 24 hours and assessed using a numerical rating scale. Electrical detection and pain thresholds, and N2-P2 evoked potentials (electroencephalography) to noxious electrical stimulation were recorded before capsaicin-induced pain (Day1-baseline), after capsaicin application (Day1-post-cap), and after 2 sessions of network-tDCS (Day2). Capsaicin induced moderate pain at Day1-post-cap, which further increased at Day2 in both groups (P = .01). Electrical detection/pain thresholds did not change over time. N2-P2 responses were reduced on Day1-post-cap compared to Day1-baseline (P = .019). At Day2 compared with Day1-post-cap, N2-P2 responses were significantly higher in the Active network-tDCS group (P<.05), while the sham group remained inhibited. These results suggest that tDCS targeting regions associated with the motor network may modulate the late evoked brain responses to noxious peripheral stimulation otherwise initially inhibited by capsaicin-induced pain. PerspectiveThis study extends the evidence of N2-P2 reduction due to capsaicin-induced pain from 30 minutes to 24 hrs. Moreover, 2 sessions of tDCS targeting the motor network in the early stage of nociceptive pain may revert the inhibition of N2-P2 associated with capsaicin-induced pain.

Supraspinal facilitation to repetitive painful stimulation: a laser-evoked potential study.

To better characterize central modulation mechanisms involved in the processing of daily repetitive painful stimulation, laser-evoked potentials (LEPs) were recorded at and away from the conditioning area in healthy participants. In addition, we aimed to evaluate a repetitive painful stimulation paradigm that could be conducted in a shorter time frame than previous studies. Collectively, continuous pain rating, warm and heat pain threshold results suggest that sensitivity to pain was reduced 24 h after the shortened repeated painful stimulation. Laser-evoked potentials revealed a significant increase in the contralateral arm to where the conditioning stimulus was applied. This finding was specific to noxious conditioning (i.e., not seen in the control brush experiment). These results provide neurophysiological evidence of pain facilitation resulting from prolonged exposure to painful heat, potentially arising in supraspinal structures.NEW & NOTEWORTHY We provide evidence for supraspinal faciliation measured via laser-evoked potentails in response to a shortened and methodologically improved repetitive painful stimulation paradigm, serving the broader scientific community, insofar as providing a paradigm can feasibly be completed in a caldendar week. These findings provide new evidence using laser-evoked potentials indicating increased activation of the anterior cingulate cortex during prolonged pain processing.

Pretreatment of the ROS Inhibitor Phenyl-N-tert-butylnitrone Alleviates Sleep Deprivation-Induced Hyperalgesia by Suppressing Microglia Activation and NLRP3 Inflammasome Activity in the Spinal Dorsal Cord

Sleep deprivation, a common perioperative period health problem, causes ocular discomfort and affects postsurgical pain. However, the mechanism of sleep deprivation-induced increased pain sensitivity is elusive. This study aims to explore the role of ROS in sleep deprivation (SD)-induced hyperalgesia and the underlying mechanism. A 48-h continuous SD was performed prior to the hind paw incision pain modeling in mice. We measured ROS levels, microglial activation, DNA damage and protein levels of iNOS, NLRP3, p-P65 and P65 in mouse spinal dorsal cord. The involvement of ROS in SD-induced prolongation of postsurgical pain was further confirmed by intrathecal injection of ROS inhibitor, phenyl-N-tert-butylnitrone (PBN). Pretreatment of 48-h SD in mice significantly prolonged postsurgical pain recovery, manifesting as lowered paw withdrawal mechanical threshold and paw withdrawal thermal latency. It caused ROS increase and upregulation of iNOS on both Day 1 and 7 in mouse spinal dorsal cord. In addition, upregulation of NLRP3 and p-P65, microglial activation and DNA damage were observed in mice pretreated with 48-h SD prior to the incision. Notably, intrathecal injection of PBN significantly reversed the harmful effects of SD on postsurgical pain recovery, hyperalgesia, microglial activation and DNA damage via the NF-κB signaling pathway. Collectively, ROS increase is responsible for SD-induced hyperalgesia through activating microglial, triggering DNA damage and enhancing NLRP3 inflammasome activity in the spinal dorsal cord.

Structural insights into the inhibition of the nsP2 protease from Chikungunya virus by molecular modeling approaches.

Chikungunya virus (CHIKV) is the etiological agent of the Chikungunya fever which has spread worldwide. Clinically, this disease may lead to prolonged incapacitating joint pain that can compromise remarkably the patients' quality of life. However, there are no licensed vaccines or specific drugs to fight this infection yet, making the search for novel therapies an imperative need. In this scenario, the CHIKV nsP2 protease emerged as an attractive therapeutic target once this protein plays a pivotal role in viral replication and pathogenesis. Hence, we investigated the structural basis for the inhibition of this enzyme by using molecular docking and dynamics simulations. Compounds with inhibitory activities against CHIKV nsP2 protease determined experimentally were selected from the literature. Docking studies with a set of stereoisomers showed that trans isomers, but not cis ones, bound close to the catalytic dyad which may explain isomerism requirements to the enzyme's inhibition. Further, binding mode analyses of other known inhibitors revealed highly conserved contacts between inhibitors and enzyme residues like N1011, C1013, A1046, Y1079, N1082, W1084, L1205, and M1242. Molecular dynamics simulations reinforced the importance of some of these interactions and pointed to nonpolar interactions as the main forces for inhibitors' binding. Finally, we observed that true inhibitors exhibited lower structural fluctuation, higher ligand efficiency and did not induce significant changes in protein correlated motions. Collectively, our findings might allow discerning true inhibitors from false ones and can guide drug development efforts targeting the nsP2 protease to fight CHIKV infections in the future.

EFFICACY OF ULTRASOUND GUIDED TRANSVERSUS ABDOMINIS PLANE BLOCK FOR POST OPERATIVE ANALGESIA IN LAPAROSCOPIC CHOLECYSTECTOMY: COMPARISON OF TWO DIFFERENT CONCENTRATION AND VOLUME OF BUPIVACAINE

Laparoscopic Cholecystectomy is one of the most common surgical procedure considered as the gold standard for the treatment of symptomatic gallbladder disease.Pain at the port sites is due to stretching by pneumoperitoneum and hepatic bed disturbances.Different techniques are in practice for postoperative analgesia. Now a days, Transversus Abdominis Plane (TAP) block is commonly performed truncal neural block owing to its high success rate, feasibility, safety and its ability to provide prolonged postoperative pain relief. In this block, local anaesthetic is inltrated between the internal oblique and transversus abdominis muscle which blocks ventral rami of lower six thoracic and upper lumbar nerves (T7 to L1) especially subcostal (T12), ilioinguinal (L1) and iliohypogastric(L1). The study was designed to evaluate the efcacy and safety of USG guided Right sided Subcostal TAP block using two different concentration and volume of Bupivacaine and their efcacy to produce postoperative analgesia in patients undergoing laparoscopic cholecystectomy.Larger volume with lower concentration of Bupivacaine (0.16%) 30 ml provides better analgesia, longer duration of effective analgesia, better hemodynamic stability and requires less analgesic consumption in postoperative period.

Sensory-motor response elicited by first time intraoral administered ethanol after trigeminal neuropathic injury.

Recent findings have shown a relationship between alcohol use disorders (AUD) and chronic pain. Preclinical models have demonstrated that chronic pain, including trigeminal nerve injury, increases ethanol consumption throughout extended administration periods. Nevertheless, it remains unclear whether chronic pain induces a greater susceptibility to developing AUD by altering motor control consumption regardless of the symptomatology of neuropathic pain, and whether sex influences this susceptibility. We used a former prolonged pain experience model induced by a constriction of the mental nerve (mNC) to answer this question. We analyzed ethanol consumption in a short-access protocol to reduce the post-ingestional effects and compared licking microstructure between groups. The constriction of the mental nerve induced evoked and spontaneous pain and reduction in the hedonic value of sucrose. The differences in alcohol consumption were not reflective of the former prolonged pain experience. Female mice showed a more efficient dynamic of consumption of alcohol, reflected in a long burst of licking and a less variable licking rate within a cluster.