Analgesic Effect Research Articles

An open-label feasibility trial of transdermal cannabidiol for hand osteoarthritis

Hand osteoarthritis (OA) is an irreversible degenerative condition causing chronic pain and impaired functionality. Existing treatment options are often inadequate. Cannabidiol (CBD) has demonstrated analgesic and anti-inflammatory effects in preclinical models of arthritis. In this open-label feasibility trial, participants with symptomatically active hand OA applied a novel transdermal CBD gel (4% w/w) three times a day for four weeks to their most painful hand. Changes in daily self-reported pain scores were measured on a 0–10 Numeric Pain Rating Scale (NPRS). Hand functionality was determined via daily grip strength measures using a Bluetooth equipped squeeze ball and self-report questionnaire. Quality of life (QoL) ratings around sleep, anxiety, stiffness and fatigue were also measured. All self-report measures and grip strength data were gathered via smartphone application. Urinalysis was conducted at trial end to determine systemic absorption of CBD. Eighteen participants were consented and 15 completed the trial. Pain ratings were significantly reduced over time from pre-treatment baseline including current pain (− 1.91 ± 0.35, p < 0.0001), average pain (− 1.92 ± 0.35, p < 0.0001) and maximum pain (− 1.97 ± 0.34, p < 0.0001) (data represent mean reduction on a 0–10 NPRS scale ± standard error of the mean (SEM)). A significant increase in grip strength in the treated hand (p < 0.0001) was observed although self-reported functionality did not improve. There were significant (p < 0.005) improvements in three QoL measures: fatigue, stiffness and anxiety. CBD and its metabolites were detected at low concentrations in all urine samples. Measured reductions in pain and increases in grip strength seen during treatment reverted back towards baseline during the washout phase. In summary, pain, grip strength and QoL measures, using smartphone technology, was shown to improve over time following transdermal CBD application suggesting feasibility of this intervention in relieving osteoarthritic hand pain. Proof of efficacy, however, requires further confirmation in a placebo-controlled randomised trial.Trial registration: ANZCTR public trials registry (ACTRN12621001512819, 05/11/2021).

Influence of Pre-treatment of Withania somnifera Root Extract and Cow Urine on Hemato-biochemical Parameters in Acetaminophen-induced Toxicity in Swiss Albino Male Mice

Background: The present study was undertaken to investigate protective activity of W. somnifera root extract (W.S.R.E.), cow urine (C.U.) and their combination against acetaminophen (APAP) induced toxicity in male mice. APAP also known as paracetamol, is a well-known drug used for its analgesic and antipyretic effects. However, outside of the therapeutic window, the toxicity may result. W.S. and C.U. are from indigenous sources of plant and animal origins, respectively with several therapeutic activities. Methods: Sixty adult swiss albino male mice were randomly divided into six groups, comprising of ten mice in each group. Group I (control group) received 2% gum acacia suspension for 14 days orally and on day 14, 0.9% NaCl (@300 mg/kg b.wt.) intraperitoneally was administered after 30 min of prior treatment of various agents. Group II, III, IV, V and VI received 2% gum acacia, silymarin (@25 mg/kg b.wt.), W.S.R.E. (@100 mg/kg b.wt.), C.U. (@7.8 mL/kg b.wt.) and W.S.R.E. (@100 mg/kg b.wt.) and C.U. (@7.8 mL/kg b.wt.) co-treatment orally for 14 days and on day 14, APAP (@300 mg/kg b.wt.) intraperitoneally was administered after 30 min of prior treatment of various agents as mentioned. On 15th day, the animals were sacrificed and samples were collected to study various hematobiochemical and growth related parameters. Result: The treatment of acetaminophen caused significant decrease in haemoglobin, total erythrocyte count whereas increase in total leucocyte and prothrombine time. There were significant (p£0.05) decreases in plasma total protein, albumin and globulin values in group II (APAP), as compared to control (group I). Treatment with W.S. +C.U attenuates these alterations. W.S.R.E., C.U. and their combination pre-treatment mildly restored the changes to normal observed following APAP exposure in mice. However, the results of co-treatment group were more pronounced as compared to individual treatment groups. Thus, it was concluded that treatment with W.S.R.E. and C.U. curtailed the toxic effect of APAP, however, co-administration of both potentiated the protective effect.

Dexmedetomidine with different concentrations added to local anesthetics in erector spinae plane block: a meta-analysis of randomized controlled trials.

Dexmedetomidine has been used as a perineural local anesthetic (LA) adjuvant to facilitate the potency of erector spinal plane block (ESPB). This quantitative review aimed to evaluate whether perineural dexmedetomidine for ESPB can improve the effects of analgesia compared to LA alone. Randomized controlled trials (RCTs) that investigated the addition of dexmedetomidine to LA compared to LA alone in ESPB were included. The pain scores, duration of sensory block, the time to first analgesia requirement, postoperative morphine consumption, rescue analgesia, and dexmedetomidine-related side effects were analyzed and combined using random-effects models. A total of 823 patients from 13 RCTs were analyzed. Dexmedetomidine was used at the concentration of 0.5 μg/kg in three trials and 1 μg/kg in nine trials, and both in one trial. Both concentrations of dexmedetomidine perineurally administrated significantly reduced the rest VAS scores postoperatively at 12 h (0.5 μg/kg dexmedetomidine: MD = -0.86; 95% CI: -1.59 to -0.12; p = 0.02; 1 μg/kg dexmedetomidine: MD = -0.49; 95% CI: -0.83 to -0.16; p = 0.004), and 24 h (0.5 μg/kg dexmedetomidine: MD = -0.43; 95% CI: -0.74 to -0.13; p = 0.005; 1 μg/kg dexmedetomidine: MD = -0.62; 95% CI: -0.84 to -0.41; p < 0.00001). Both concentrations of dexmedetomidine added in LAs improved the dynamic VAS scores postoperatively at 12 h (0.5 μg/kg dexmedetomidine: MD = -0.55; 95% CI: -0.95 to -0.15; p = 0.007; 1 μg/kg dexmedetomidine: MD = -0.66; 95% CI: -1.05 to -0.28; p = 0.0006) and 24 h (0.5 μg/kg dexmedetomidine: MD = -0.52; 95% CI: -0.94 to -0.10; p = 0.01; 1 μg/kg dexmedetomidine: MD = -0.46; 95% CI: -0.75 to -0.16; p = 0.002). Furthermore, perineural dexmedetomidine prolonged the duration of the sensory block and the time to first analgesia requirement, reduced postoperative morphine consumption, and lowered the incidence of rescue analgesia and chronic pain. The meta-analysis showed that using perineural dexmedetomidine at either 0.5 μg/kg or 1 μg/kg doses in ESPB can effectively and safely enhance pain relief. PROSPERO (CRD42023424532: https://www.crd.york.ac.uk/PROSPERO/).

Tropane Alkaloid Isolated from Erythroxylum bezerrae Exhibits Neuropharmacological Potential in an Adult Zebrafish (Danio rerio) Model.

This study carried out to investigate the anti-inflammatory and antinociceptive effect of tropane alkaloid (EB7) isolated from E. bezerrae. It evaluated the toxicity and possible involvement of ion channels in the antinociceptive effect of EB7, as well as its anti-inflammatory effect in adult zebrafish (Zfa). Docking studies with EB7 and COX-1 and 2 were also performed. The tested doses of EB7 (4, 20 and 40 mg/kg) did not show any toxic effect on Zfa during the 96h of analysis (LD50 > 40 mg/kg). They did not produce any alteration in the locomotor behavior of the animals. Furthermore, EB7 showed promising pharmacological effects as it prevented the nociceptive behavior induced by hypertonic saline, capsaicin, formalin and acid saline. EB7 had its analgesic effect blocked by amiloride involving the neuromodulation of ASICs in Zfa. In evaluating the anti-inflammatory activity, the edema induced by κ-carrageenan 3.5% was reduced by the dose of 40 mg/kg of EB7 observed after the fourth hour of analysis, indicating an effect similar to that of ibuprofen. Molecular docking results indicated that EB7 exhibited better affinity energy when compared to ibuprofen control against the two evaluated targets binding at different sites in the cocrystallized COX-1 and 2 inhibitors.

Study on quality control methods and pharmacodynamic material basis of different specifications of Corydalis Rhizoma produced in Zhejiang Province

Ethnopharmacological relevanceThe quality control methods of different specifications of Corydalis Rhizoma in Zhejiang China (ZJ CR) are the same, so the quality of each specification couldnot be guaranteed. To clarify the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications could provide reference for the quality control of ZJ CR. Aim of the studyThe purpose of this study was to establish a quality control method for ZJ CR with different specifications and to screen out the pharmacodynamic material basis of ZJ CR with different specifications. Materials and methodsFirstly, according to the existing grading standards, the medicinal materials were divided into specifications, and the character indexes of ZJ CR with different specifications were established. The quality indexes were established by HPLC, network pharmacology and literature retrieval. The correlation between the trait indexes and quality indexes of ZJ CR with different specifications was analyzed, and the best quality control method was established. Further combined with the pharmacodynamic indexes of ZJ CR with different specifications, the pharmacodynamic material basis of ZJ CR with different specifications was screened out by spectrum-effect analysis. The correlation between trait indexes and pharmacodynamic indexes was analyzed to verify the rationality of grade standard. ResultsThe three specifications of ZJ CR were CR (Diameter ≥1.1 cm), CR (Diameter <1.1 cm), and CR (No size distinction). Diameter, width, thickness, grain weight, volume and 50 g grain number could be used as the trait indexes of ZJ CR. Protopine (CR1), palmatine hydrochloride (CR2), berberine hydrochloride (CR3), dehydrocorydaline (CR4), tetrahydropalmatine (CR5), tetrahydroberberine (CR6), corydaline (CR7), stylopine (CR8) and isoimperatorin (CR9) were identified. Total components, core components (CR5, CR6, CR7 and CR8), alcohol-soluble extracts (ASE) could be used as quality indexes. The best quality control methods of the three specifications respectively were: the larger the diameter and grain weight, the smaller the number of 50 g grains; The larger the diameter, the smaller the volume, thickness, width and number of 50 g particles; The larger the grain weight and volume, the smaller the number of 50 g grains. The main analgesic components of the three specifications respectively were: CR1, CR2 and core components; CR2, CR4; CR8, CR9. The larger the diameter and the less the number of 50 g grains, the better the analgesic effect of ZJ CR, and the grade standard was reasonable. ConclusionsThis study showed that the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications were different, which may be caused by the differences in traits and the contribution of main active ingredients. This study constructed an evaluation model combining external traits, internal quality and overall efficacy, and provided theoretical support for the rationality of ZJ CR grade standard.

Investigation of the analgesic effects of rhomboid intercostal and pectoral nerve blocks in breast surgery.

The objective of this study was to examine the hypothesis that the opioid consumption of patients who receive a rhomboid intercostal block (RIB) or a pectoral nerve (PECS) block after unilateral modified radical mastectomy (MRM) surgery is less than that of patients who receive local anesthetic infiltration. Eighty-one female patients aged 18-70years who underwent unilateral MRM surgery with general anesthesia were randomly allocated to three groups. The first group received an RIB with 30ml of 0.25% bupivacaine on completion of the surgery, and the second received a PECS block with the same volume and concentration of local anesthetic. In the third (control) group, local infiltration was applied to the wound site with 30ml of 0.25% bupivacaine at the end of the surgery. The patients' total tramadol consumption, quality of recovery (QoR), postoperative pain scores, and sleep quality were evaluated in the first 24h postoperatively. Both the RIB (58.3 ± 22.8mg) and PECS (68.3 ± 21.2mg) groups had significantly lower tramadol consumption compared to the control group (92.5 ± 25.6mg) (p < 0.001 and p = 0.002, respectively). Higher QoR scores were observed in the RIB and PECS groups than the control group at 6h post-surgery. The lowest pain values were observed in the RIB group. The sleep quality of the patients in the RIB and PECS groups was better than that of the control group (p < 0.001). Compared to local anesthetic infiltration, the RIB and PECS blocks applied as part of multimodal analgesia in MRM surgery reduced opioid consumption in the first 24h and improved the quality of recovery in the early period.

Application of multimodal standardized analgesia under the concept of enhanced recovery after surgery in laparoscopic radical colorectal cancer surgery.

To observe the efficacy and safety of multimodal standardized analgesia in patients undergoing laparoscopic radical colorectal cancer surgery. A prospective, double-blind, randomized study of patients who were admitted to our hospital between December 2020 and March 2022 with a diagnosis of colorectal cancer and who intended to undergo elective laparoscopic radical colorectal cancer surgery was conducted. The participants were randomly divided into two intervention groups, namely, a multimodal standardized analgesia group and a routine analgesia group. In both groups, the visual analogue scale (VAS) pain scores while resting at 6h, 24h, 48h and 72h and during movement at 24h, 48h and 72h; the number of patient controlled intravenous analgesia (PCIA) pump button presses and postoperative recovery indicators within 3 days after surgery; the interleukin-6 (IL-6) and C-reactive protein (CRP) levels on the 1st and 4th days after surgery; and the incidence of postoperative adverse reactions and complications were recorded. Compared with the control group, the multimodal standardized analgesia group had significantly lower VAS pain scores at different time points while resting and during movement (P<0.05), significantly fewer PCIA pump button presses during the first 3 postoperative days (P<0.05), and significantly lower IL-6 and CRP levels on the 1st postoperative day (P<0.05). There was no statistically significant difference in the time to out-of-bed activity, the time to first flatus, the IL-6 and CRP levels on the 4th postoperative day or the incidence of postoperative adverse reactions and complications between the two groups (P >0.05). For patients undergoing laparoscopic radical colorectal cancer surgery, multimodal standardized analgesia with ropivacaine combined with parecoxib sodium and a PCIA pump had a better analgesic effect, as it effectively inhibited early postoperative inflammatory reactions and promoted postoperative recovery and did not increase the incidence of adverse reactions and complications. Therefore, it is worthy of widespread clinical practice.

Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study.

Yokukansan, a traditional Japanese medicine (Kampo), has been widely used to treat neurosis, dementia, and chronic pain. Previous in vitro studies have suggested that Yokukansan acts as a partial agonist of the 5-HT1A receptor, resulting in amelioration of chronic pain through inhibition of nociceptive neuronal activity. However, its effectiveness for treating postoperative pain remains unknown, although its analgesic mechanism of action has been suggested to involve serotonin and glutamatergic neurotransmission. This study aimed to investigate the effect of Yokukansan on postoperative pain in an animal model. A mouse model of postoperative pain was created by plantar incision, and Yokukansan was administered orally the day after paw incision. Pain thresholds for mechanical and heat stimuli were examined in a behavioral experiment. In addition, to clarify the involvement of the serotonergic nervous system, we examined the analgesic effects of Yokukansan in mice that were serotonin-depleted by para-chlorophenylalanine (PCPA) treatment and intrathecal administration of NAN-190, 5-HT1A receptor antagonist. Orally administered Yokukansan increased the pain threshold dose-dependent in postoperative pain model mice. Pretreatment of para-chlorophenylalanine dramatically suppressed serotonin immunoreactivity in the spinal dorsal horn without changing the pain threshold after the paw incision. The analgesic effect of Yokukansan tended to be attenuated by para-chlorophenylalanine pretreatment and significantly attenuated by intrathecal administration of 2.5µg of NAN-190 compared to that in postoperative pain model mice without para-chlorophenylalanine treatment and NAN-190 administration. This study demonstrated that oral administration of Yokukansan has acute analgesic effects in postoperative pain model mice. Behavioral experiments using serotonin-depleted mice and mice intrathecally administered with a 5-HT1A receptor antagonist suggested that Yokukansan acts as an agonist at the 5-HT1A receptor, one of the serotonin receptors, to produce analgesia.

Ultrasound guided quadratus lumborum block versus interlaminar epidural block for analgesia in pediatric abdominal surgery: a randomized controlled trial

BackgroundAlthough the efficacy and safety of epidural block (EB) are fairly high, complications such as inadvertent dural puncture may limit its use. Ultrasound-guided quadratus lumborum block (QLB) is a relatively new regional technique that provides perioperative somatic and visceral analgesia for pediatric patients. This trial compared the quality of pain relief in pediatric patients undergoing abdominal surgery who received either QLB or EB.MethodsPatients were randomly allocated into two equal groups: Group E(n = 29): received EB; Group QL(n = 29): received QLB. Both groups were injected with 0.25% bupivacaine (0.5 ml/kg). Assessment of total analgesia consumption was the primary outcome measure, whereas the secondary outcome measures were assessment of postoperative analgesic effect by Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) and time of first analgesic request.ResultsOur study showed that the mean total fentanyl consumption was comparable between both groups(38.67 ± 5.02 and 36.47 ± 5.13 µg in the E and QL groups, respectively, P = 0.246). Only five patients did not require rescue analgesia (3 in the E group,2 in the QL group, P = 0.378). The mean duration of analgesia showed no significant difference between the two groups (9.9 ± 1.58 and 11.02 ± 1.74 h in the E and QL groups, respectively, P = 0.212). Evaluation of CHEOPS score values immediately in PACU and for the initial 24 h following operation showed no significant difference between the two study groups(P > 0.05).ConclusionQLB can achieve analgesic effects comparable to those of EB as a crucial part of multimodal analgesia in children undergoing abdominal surgeries.Clinical trial registration numberPACTR202203906027106.

Tegileridine: First Approval.

Tegileridine () is a small molecule μ-opioid receptor biased agonist developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd for the treatment of postoperative pain. Tegileridine selectively activates the G-protein-coupled pathway, which mediates strong central analgesic effects and only weakly activates the β-arrestin-2 pathway implicated in adverse events like respiratory depression and gastrointestinal dysfunction. In January 2024, tegileridine received its first approval in China for the treatment of moderate to severe pain after abdominal surgery. This article summarizes the milestones in the development of tegileridine leading to this first approval for the treatment of moderate to severe pain after abdominal surgery.

Investigating neuroepigenetic alterations in chronic low back pain with positron emission tomography.

Epigenetics has gained considerable interest as potential mediators of molecular alterations that could underlie the prolonged sensitization of nociceptors, neurons, and glia in response to various environmental stimuli. Histone acetylation and deacetylation, key processes in modulating chromatin, influence gene expression; elevated histone acetylation enhances transcriptional activity, whereas decreased acetylation leads to DNA condensation and gene repression. Altered levels of histone deacetylase (HDAC) have been detected in various animal pain models, and HDAC inhibitors have demonstrated analgesic effects in these models, indicating HDACs' involvement in chronic pain pathways. However, animal studies have predominantly examined epigenetic modulation within the spinal cord after pain induction, which may not fully reflect the complexity of chronic pain in humans. Moreover, methodological limitations have previously impeded an in-depth study of epigenetic changes in the human brain. In this study, we employed [11C]Martinostat, an HDAC-selective radiotracer, positron emission tomography to assess HDAC availability in the brains of 23 patients with chronic low back pain (cLBP) and 11 age-matched and sex-matched controls. Our data revealed a significant reduction of [11C]Martinostat binding in several brain regions associated with pain processing in patients with cLBP relative to controls, highlighting the promising potential of targeting HDAC modulation as a therapeutic strategy for cLBP.

Laparoscopic-Guided Transversus Abdominis Plane (TAP) Block Combined with Port-Site Infiltration (PSI) for Laparoscopic Sleeve Gastrectomy in an ERABS Pathway: A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial.

Patients undergoing laparoscopic sleeve gastrectomy (LSG) commonly experience moderate to severe postoperative pain. We conducted a randomized, prospective double-blind placebo-controlled study to evaluate the analgesic effect of laparoscopic-guided TAP (LG-TAP) block after LSG in a high-volume bariatric center, applying an enhanced recovery after bariatric surgery (ERABS) pathway. One hundred ten patients were randomly allocated to receive LG-TAP block with local anesthetic (LA) or saline solution (placebo), both combined with port-site infiltration with LA (LA-PSI). Primary outcome was pain score measured in post-anesthesia care unit (PACU) and at 6, 12, and 24 h after surgery. Secondary outcomes included postoperative nausea and/or vomiting (PONV), analgesic requirement, time to walking, time to flatus, length of hospital stay (LOS), and surgical complications. No significant differences were observed between LG-TAP and placebo groups in postoperative analgesia, with a median (IQR) NRS of 2 (4.75-0) vs. 2 (5.25-0) in PACU, 5.5 (7-3) vs. 6 (7-4) at 6 h, 2 (6-0) vs. 3 (5.25-1.75) at 12 h, and 2 (3.75-0) vs. 1 (2-0) at 24 h; all p > 0.05. A significant difference was found in PONV in PACU (LG-TAP, 46%; placebo, 25%, p-value, 0.019) and at 6 h postoperatively (LG-TAP, 69%, placebo, 41%, p-value, 0.003). No differences were observed as regards other secondary outcomes. Our results suggest that LG-TAP block is not related to more effective postoperative analgesia compared to placebo when LA-PSI is performed.

Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel.

Chronic orofacial pain (COP) therapy is challenging, as current medical treatments are extremely lacking. Moutan Cortex (MC) is a traditional Chinese medicine herb widely used for chronic inflammatory diseases. However, the mechanism behind MC in COP therapy has not been well-established. The purpose of this study was to identify the active ingredients of MC and their specific underlying mechanisms in COP treatment. In this study, the main active ingredients and compound-target network of MC in COP therapy were identified through network pharmacology and bioinformatics analysis. Adult male Sprague-Dawley rats received oral mucosa lipopolysaccharide (LPS) injection to induce COP. Pain behaviors were evaluated by orofacial mechanical nociceptive assessment after intraganglionar injection. In vitro inflammatory cytokines in LPS-pretreated human periodontal ligament stem cells (hPDLSCs) and rat primary cultural trigeminal ganglion (TG) neurons were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Schrödinger software was used to verify the molecular docking of quercetin and critical targets. Whole-cell recording electrophysiology was used to evaluate the effect of quercetin on voltage-gated sodium (Na v ) channel in rat TG neurons. The assembled compound-target network consisted of 4 compounds and 46 targets. As 1 of the active components of MC correlated with most related targets, quercetin alleviated mechanical allodynia in LPS-induced rat model of COP (mechanical allodynia threshold median [interquartile range (IQR) 0.5 hours after drug administration: vehicle 1.3 [0.6-2.0] g vs quercetin 7.0 [6.0-8.5] g, P = .002). Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that immune response and membrane functions play essential roles in MC-COP therapy. Five of the related targets were identified as core targets by protein-protein interaction analysis. Quercetin exerted an analgesic effect, possibly through blocking Na v channel in TG sensory neurons (peak current density median [IQR]: LPS -850.2 [-983.6 to -660.7] mV vs LPS + quercetin -589.6 [-711.0 to -147.8] mV, P = .006) while downregulating the expression level of proinflammatory cytokines-FOS (normalized messenger RNA [mRNA] level mean ± standard error of mean [SEM]: LPS [2. 22 ± 0.33] vs LPS + quercetin [1. 33 ± 0.14], P = .034) and TNF-α (normalized mRNA level mean ± SEM: LPS [8. 93 ± 0.78] vs LPS + quercetin [3. 77 ± 0.49], P < .0001). Identifying Na v as the molecular target of quercetin clarifies the analgesic mechanism of MC, and provides ideas for the development of novel selective and efficient chronic pain relievers.

Long-term use of intrathecal baclofen reduces neuropathic pain and its interference with general activity in spinal cord injury individuals.

Long-term analgesic effect of intrathecal baclofen was reported in individuals with spinal cord injury. We conducted a prospective study to evaluate the effect of intrathecal baclofen on subtypes of neuropathic pain and its interference with general activity. Nine spinal cord injury individuals who presented with severe spasticity and moderate to severe neuropathic pain received intrathecal baclofen via an implanted pump. We applied the ASIA Impairment Scale to assess spinal cord injury severity. Neuropathic pain was evaluated by numerical rating scale, Neuropathic Pain Symptom Inventory, and Brief Pain Inventory. Evaluations were performed at baseline and after at least 6months of continuous intrathecal baclofen treatment. Intrathecal baclofen led to significant pain reduction as measured by numerical rating scale, Neuropathic Pain Symptom Inventory, and Brief Pain Inventory (p < 0.05). Improvements were significant for paroxysmal pain and dysesthesia and for pain interference with general activity, as assessed by the Brief Pain Inventory (p < 0.05). There was a significant relationship between the time since spinal cord injury and changes in paroxysmal pain as well as in the total Neuropathic Pain Symptom Inventory score (p < 0.05). The baclofen dose correlated also to the percentage changes in neuropathic pain improvement and sleep (p < 0.003). The present results provide evidence that intrathecal baclofen effectively reduces neuropathic pain, particularly paroxysmal pain and dysesthesia, and improves pain interference and overall well-being in individuals with spinal cord injury. Clinicians should be aware of this less well-known beneficial effect of intrathecal baclofen and should consider such a treatment option for better control of neuropathic pain in individuals with spinal cord injury.

To elucidate the bioactive components of Lamiophlomis herba in the treatment of liver fibrosis via plasma pharmacochemistry and network pharmacology

Lamiophlomis Herba (LH) is a traditional Chinese and Tibetan dual-use herb with hemostatic and analgesic effects, and is widely used in the clinical treatment of traumatic bleeding and pain. In recent years, LH has been proven to treat liver fibrosis (LF), but the chemical components related to the pharmacological properties of LH in the treatment of LF are still unclear. Based on the theory of plasma pharmachemistry, the characteristic components in water extract and drug-containing plasma samples of LH were qualitatively analyzed by UPLC-Q-TOF-MS. The chemical components in plasma were screened and the targets were predicted by network pharmacology. Then, the predicted components and targets were verified in vitro by Elisa and qRT-PCR technology. Finally, the pharmacological effects of LH and its monomeric components were determined by hematoxylin-eosin staining of rat liver. A total of 50 chemical constituents were identified in LH, of which 12 were blood prototypes and 9 were metabolites. In vitro experiments showed that LH and its monomeric components luteolin, shanzhiside methyl ester, loganic acid, loganin, 8-O-acetyl shanzhiside methyl ester could increase the expression of antioxidant genes (NQO-1, HO-1) and decrease the expression of inflammatory genes (IL-6, IL-18), thereby reducing the expression of extracellular matrix-related genes and proteins (COL1A1, COL3A1, LN, α-sma, PC-III, Col-IV). In vivo experiments showed that LH could reduce the area of LF in rats in a dose-dependent manner, and shanzhiside methyl ester and 8-O-acetyl shanzhiside methyl ester may be the main components in pharmacodynamics. These effects may be mediated by LH-mediated Nrf2/NF-κB pathway. This study explored the potential pharmacodynamic components of LH in the treatment of LF, and confirmed that shanzhiside methyl ester and 8-O-acetyl shanzhiside methyl ester play a key role in the treatment of LF with LH.

Comparative analysis of the course of the perioperative period in patients with diabetes during knee and hip arthroplasties

Background. Hip and knee arthroplasty (HKA) are common surgical interventions. In more than 20 % of patients undergoing HKA, diabetes mellitus is detected, which is one of the risk factors for the development of periprosthetic infection and the occurrence of complications in the perioperative period. The purpose: to determine the features of the course of the perioperative period in patients with diabetes during knee and hip replacement. Materials and methods. A retrospective analysis was performed of the inpatient charts of 50 people who underwent HKA against the background of concomitant diabetes. All participants were divided into two groups: 1) patients with hip arthroplasty; 2) patients with knee arthroplasty. The course of the intraoperative and postoperative periods and the development of complications were analyzed. Results. All patients were aged from 38 to 86 years, had increased weight (body mass index of 26.0–29.4 kg/m2). Among the complications, hypertension was most common (64.0 and 68.0 % in the groups, respectively), nausea and vomiting (32.0 and 28.0 %, respectively), disturbances in the rhythm and depth of breathing (16.0 and 20.0 % respectively) were often observed. The need for analgesia in the postoperative period was registered in 96.0 and 100.0 % of cases, which indicates its insufficient quality. Other clinical and anamnestic indicators, the course of the perioperative period and the development of complications were similar in patients undergoing both hip and knee replacements (p &gt; 0.05). Conclusions. Clinical and anamnestic data, the spectrum of existing concomitant pathology, characteristics of carbohydrate metabolism and its disorders, features of the course of the perioperative period and detected complications were of the same type in patients regardless of the location of the intervention. There was no significant difference in the studied parameters (p &gt; 0.05). Identified complications and insufficient effectiveness of postoperative analgesia dictates the need to find optimal methods of perioperative analgesia during HKA.

Brucine Sulfate, a Novel Bacteriostatic Agent in 3D Printed Bone Scaffold Systems.

Bacterial infection is a common complication in bone defect surgery, in which infection by clinically resistant bacteria has been a challenge for the medical community. Given this emerging problem, the discovery of novel natural-type inhibitors of drug-resistant bacteria has become imperative. Brucine, present in the traditional Chinese herb Strychnine semen, is reported to exert analgesic and anti-inflammatory effects. Brucine's clinical application was limited because of its water solubility. We extracted high-purity BS by employing reflux extraction and crystallization, greatly improved its solubility, and evaluated its antimicrobial activity against E. coli and S. aureus. Importantly, we found that BS inhibited the drug-resistant strains significantly better than standard strains and achieved sterilization by disrupting the bacterial cell wall. Considering the safety concerns associated with the narrow therapeutic window of BS, a 3D BS-PLLA/PGA bone scaffold system was constructed with SLS technology and tested for its performance, bacteriostatic behaviors, and biocompatibility. The results have shown that the drug-loaded bone scaffolds had not only long-term, slow-controlled release with good cytocompatibility but also demonstrated significant antimicrobial activity in antimicrobial testing. The above results indicated that BS may be a potential drug candidate for the treatment of antibiotic-resistant bacterial infections and that scaffolds with enhanced antibacterial activity and mechanical properties may have potential applications in bone tissue engineering.

Discovery of first-in-class highly selective TRPV1 antagonists with dual analgesic and hypoglycemic effects

Analgesia and blood sugar control are considered as two main unmet clinical needs for diabetes related neuropathic pain patients. Transient receptor potential vanilloid type-1 (TRPV1) channel is a highly validated target for pain perception, while no TRPV1 antagonists have been approved due to hyperthermia side effects. Herein, two series of new TRPV1 antagonists with flavonoid skeleton were designed by the structure-based drug design (SBDD) strategy. After comprehensive evaluation, compound CX-3 was identified as a promising TRPV1 antagonist. CX-3 exhibited equivalent TRPV1 antagonistic activity with classical TRPV1 antagonist BCTC in vitro, and exerted better analgesic activity in vivo than that of BCTC in the formalin induced inflammatory pain model without hyperthermia risk. Moreover, CX-3 exhibited robust glucose-lowering effects and showed high selectivity over other ion channels. Overall, these findings identified a first-in-class highly selective TRPV1 antagonist CX-3, which is a promising candidate to target the pathogenesis of diabetes related neuropathic pain.

Postsurgical Analgesic Effectiveness of Ultrasound-Guided Parasternal Block After Auricular Reconstruction Using Autologous Costal Cartilage in Pediatric Patients: A Randomized Controlled Trial.

To study the efficacy of ultrasound-guided parasternal block (US-PSI) in pediatric patients undergoing auricular reconstruction surgery. For this study, the authors recruited 60 children between the ages of 5 and 12 years who underwent auricular reconstruction with autologous costal cartilage (ACC) to correct microtia. They were randomized to receive either ultrasound-guided modified parasternal block or periprostatic local infiltration anesthesia (PLIA), with 30 cases in each group. Ultrasound-guided parasternal block was administered following anesthesia induction, whereas PLIA was administered after ACC harvest. Lastly, following surgery, all children were provided with patient-controlled intravenous analgesia with sufentanil, and the numeric pain rating scale (NRS) was used to assess the intensity of pain. Our primary outcomes were the resting NRS pain scores and the NRS scores upon coughing at 1, 6, 12, 24, and 48 hours postsurgery. Sufentanil consumption within the first 24 hours of surgery, the mean duration to first ambulation, and the usage of rescue analgesics were our secondary outcomes. The authors also recorded the occurrence of undesirable side effects as well as more serious side effects like pneumothorax. Pediatric patients who were administered US-PSI showed significantly reduced NRS chest pain scores at 6 and 12 hours postsurgery compared to those who received PLIA (P<0.05). In addition, sufentanil consumption within the first 24 hours postsurgery, duration to first ambulation, and use of rescue analgesics were significantly lower among patients in the US-PSI group when compared to those in the PLIA group (P<0.05). This study found that US-PSI was a highly efficacious and safe technique for postsurgical analgesia following auricular reconstruction with ACC in pediatric patients. Level II, therapeutic study.

Author response to ‘Comparing analgesic effect of regional block after hip arthroscopy’

Author response to ‘Comparing analgesic effect of regional block after hip arthroscopy’