Analgesic Effect Research Articles

Effectiveness of tramadol-including multimodal analgesia in spinal surgery: a single-center, retrospective cohort study

BackgroundMultimodal analgesia (MMA) is recommended for postoperative pain management; however, studies evaluating the effect of tramadol-including MMA on numerical rating scale (NRS)-based postoperative pain levels and the length of stay (LOS) in the hospital are limited. Therefore, this study aimed to compare the before and after effects of tramadol-including MMA application, and assess its effect on postoperative NRS scores and LOS.MethodsPatients who underwent spinal surgery under general anesthesia at the Rakuwakai Marutamachi Hospital in fiscal years 2020 and 2022 were included in this study. The outcomes between the pre- and post-intervention groups were compared through propensity score matching.ResultsFollowing propensity score matching, 249 patients were included in each group. MMA application significantly decreased the median LOS from 10 to 9 days (p < 0.001). Additionally, the median NRS scores exhibited a significant decrease from 4 to 3 on postoperative day (POD) 3 (p = 0.0109) and from 3 to 2 on POD 5 (p = 0.0087). Following MMA application, the number of patients receiving additional analgesics decreased significantly, from 38 to 6 (p < 0.001).ConclusionsThe introduction of tramadol-including MMA can effectively reduce postoperative pain and decrease the LOS for patients undergoing spinal surgery.

Assessment of the onset of analgesia and length of analgesia following the use of PBM with different wavelengths: a clinical study

This clinical study assessed photobiomodulation (PBM) induced analgesic effects of diode lasers and an LED light source on the dental pulp. Baseline responses to electric pulp testing (EPT) were recorded in 93 healthy unrestored premolar teeth in 26 adults (age range 22–63 years) attending a private dental practice. The teeth were irradiated on buccal and lingual aspects of the crown, by placing the tips on the middle third of the crown of the teeth, on separate days for each of 4 different light sources (660, 808, or 904 nm diode lasers, or a novel multi-wavelength LED light source (700–1100 nm)) using comparable parameters (100 mW, 30 s, 6 J). EPT scores were measured after a further 1-, 2-, 5- and 20-min. Discomfort caused by PBM therapy was recorded using the Wong-Baker scale. EPT changes were tracked over time using repeated measures analysis of variance. Baseline EPT scores were very consistent between different days (linear regression r2 0.9422–0.9648). All PBM devices caused a significant elevation in EPT at 5 min, with an earlier onset at 2 mins for 904 nm and LED. The LED was the only light source that elevated scores at 20 min. Across 2–20 min, when ranked by effectiveness, the greatest EPT elevations were seen for LED, followed by 904 nm, then 660 nm and finally 808 nm. Discomfort during PBM was most common with 904 nm, followed by 808 nm. No discomfort occurred from the LED. Among the light sources utilized, the LED multi-wavelength system demonstrated the largest increase in EPT readings, suggesting its potential as a non-pharmacological alternative for achieving dental analgesia compared to diode lasers.

Comparison of ropivacaine with ropivacaine–dexamethasone combination for postoperative analgesia in the pectoral nerve block for modified radical mastectomy: A randomized clinical trial

Abstract Background and Aims: The pectoral nerve block types I and II are novel techniques to provide analgesia for modified radical mastectomy (MRM) surgeries performed under general anesthesia. The primary objective of this study was to compare the duration of effective analgesia, and the secondary objectives were to evaluate the total amount of rescue analgesics in 24 h, hemodynamic changes, and postoperative adverse effects. Methods: This prospective, randomized, double-blind study was conducted on a total of 80 women with breast cancer belonging to American Society of Anesthesiologist class I and II scheduled for MRM, which were randomly allocated into two groups – Group R (n = 40) received 0.25% ropivacaine 29 ml + NS 1 ml and Group RD (n = 40) received 0.25% ropivacaine 29 ml + dexamethasone (4 mg) 1 ml. Ten milliliters of the study drug was used in Pecs I and the rest 20 ml in Pecs II block posttumor resection. Results: The duration of analgesia was statistically significantly longer in RD (778.75 ± 55.12 min) compared to Group R (412.63 ± 21.69 min) (P &lt; 0.05). Pain scores were significantly less in Group RD. The mean dose of acetaminophen required was significantly less in Group RD (2362.50 ± 375.32 mg) than in Group R (3525.00 ± 298.50 mg) (P &lt; 0.05). The incidence of adverse events was similar in both groups. Conclusion: The addition of dexamethasone with ropivacaine in the Pecs block can be used for prolonging the effective duration of analgesia and decreasing postoperative analgesic consumption with comparable hemodynamic and side effect profiles.

Pharmacognostic and Pharmacological Study of "Azadirachta Indica" Bark Extracts

Azadiracta indica A. Juss (Meliaceae) commonly known as Neem,is found throughout India and is known to have many wonderous properties from ancient times.These A.indica shows different medicinal properties like antiulcerogenic, hypoglycemic, insecticidal, spermicidal actions. The stem bark was studied for morphological as well as microscopical characteristics. The present work was carried out on bark of Azadirachta indica belonging to family Meliaceae. The study was done on pharmacognostic, phytochemical and pharmacological studies on stems bark of Azadirachta indica collected from Sangamner of Ahmednagar district. Preliminary phytochemical screening of extract was done.Some part of extract was then used to study pharmacological screening of anti-anxiety activity.From the study of phytochemical and pharmacological investigation of Azadirachta indica bark it was found that different chemicals are present as glycosides, alkaloids, tannins, fats, steroids, proteins, etc. Azadirachta indica stem bark supports the elimination of related anxiety associated materials. Therefore, drawing conclusions from this research suggests that Azadirachta indica hydroethanolice etract were found to be with good antianxiety like activity in elevated plus maze model. Furthermore, this current study confirms the conventional utilisation of Azadirachta indica bark as a pain reliever by showing that its hydroethanolic determine has noteworthy analgesic properties for various dose amounts, with the greatest analgesic movement observed at a 60-minute time interval. More research is required, nevertheless, to determine how precisely it exerts its analgesic effects.

Ultrasound-guided bilateral anterior quadratus lumborum block at the lateral supra-arcuate ligament in patients undergoing laparoscopic radical gastrectomy: A randomised controlled study

Objective: Ultrasound-guided bilateral anterior quadratus lumborum block at the lateral supra-arcuate ligament has recently been proposed as an effective analgesia for abdominal surgery. To test the hypothesis that this novel technique was a viable alternative approach of conventional thoracic epidural analgesia for laparoscopic radical gastrectomy. Methods: Three hundred patients scheduled for laparoscopic radical gastrectomy were randomised 1:1 into the anterior quadratus lumborum block group: receiving the novel regional analgesia, and the thoracic epidural analgesia group: receiving thoracic epidural anaesthesia. The primary endpoint was intraoperative consumption of propofol and remifentanil. Intention-to-treat analysis was performed for all variables. Results: At five and ten minutes after block, anterior quadratus lumborum block group achieved more dermatomes coverage of the sensory block with both p &lt; 0.001. Intraoperative consumption of propofol and remifentanil was comparable between two groups (1116.21 ± 199.76 versus 1166.45 ± 125.31µg, p = 0.245 and remifentanil 1.83 ± 0.41 versus 1.81 ± 0.37ng, p = 0.988). However, anterior quadratus lumborum block group was associated with less intraoperative consumption of norepinephrine and atropine, shorter time to urinary catheter removal and out-of-bed activity than the thoracic epidural anaesthesia group. No significant difference in extubation time, pain scores at rest and exercising at all time points following surgery was observed between the two groups. Conclusions: Compared with conventional thoracic epidural anaesthesia, the novel technique was an equivalent effective component of multimodal analgesic protocol for laparoscopic radical gastrectomy. There were some advantages, including shorter procedure time, more reliable dermatomal coverage, shorter duration of urinary catheterisation and earlier time of out-of-bed activity to enhance recovery after surgery. Trial registration: The study was registered in the Chinese Clinical Trial Registry on 2 November 2022 (ChiCTR2200065325).

Pharmacokinetics and thermal anti-nociceptive effects of oral morphine in horses

IntroductionMorphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed.MethodsSix horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat.ResultsThe maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration.DiscussionResults of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses.

Evaluating the Efficacy of Wrist-Ankle Acupuncture Combined With Patient-Controlled Intravenous Analgesia for Managing Post Uvulopalatopharyngoplasty.

The aim of this study is to investigate the impact of combining wrist-ankle acupuncture with patient-controlled intravenous analgesia (PCIA) on active pain and food intake in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) after undergoing uvulopalatopharyngoplasty (UPPP). Sixty patients with OSAHS who underwent UPPP at our hospital's Department of Otorhinolaryngology from January 2020 to October 2023 were selected and randomly divided into 2 groups of 30 each: an observation group and a control group. The control group received general anesthesia administered by an anesthesiologist and used a PCIA pump. In addition to this treatment, the observation group received the combined intervention of wrist-ankle acupuncture. Active pain levels were monitored at 0, 6, 12, 24, 36, and 48 hours after UPPP, and food intake was observed at 24, 36, and 48 hours postoperation. The results were compared and recorded for both groups. The analgesic effect on active pain in the observation group was significantly greater than in the control group at 6, 12, 24, 36, and 48 hours postoperation, and the differences were statistically significant (P<0.05). In addition, when comparing food intake scores at 24, 36, and 48 hours postoperation, the observation group had significantly higher food intake than the control group, and the differences were statistically significant (P<0.05). The combined intervention of wrist-ankle acupuncture and PCIA provides effective pain relief for OSAHS patients after UPPP, enhances their food intake, improves their quality of life, and supports early recovery.

Effect of parecoxib on postoperative cognitive function and analgesic safety in elderly patients undergoing gastrointestinal tumor resection: A retrospective study.

Neuroinflammation is associated with the development of postoperative cognitive dysfunction (POCD). Parecoxib has powerful anti-inflammatory and analgesic effects, which may reduce the occurrence of POCD. We hypothesized that parecoxib could reduce the incidence of POCD and relieve postoperative pain without increasing postoperative complications in elderly patients with gastrointestinal cancer. The study analyzed the effect of parecoxib on elderly patients undergoing elective radical resection of gastrointestinal tumors. Patients were divided into the NSAIDs group and the non-NSAIDs group according to whether parecoxib was administered. Demographic and clinical data were collected and compared. The incidence of POCD was set as the primary outcome, and postoperative pain as the secondary outcome. Among the 440 enrolled patients, the POCD incidence rates within 7 days after surgery in the NSAIDs and non-NSAIDs groups were 42.60% and 40.30%, respectively, with no statistically significant difference (P > 0.05). Patients in the NSAIDs group experienced significantly less pain on the first and second days after surgery compared to the non-NSAIDs group (P < 0.05). There were no statistically significant differences in postoperative adverse events between the two groups (P > 0.05). Parecoxib had no significant negative effect on early postoperative cognitive function, effectively alleviating early postoperative acute pain without increasing postoperative complications. The findings have implications for the broader use of parecoxib in postoperative pain management in elderly patients undergoing major surgery.

Mentha arvensis oil exhibits repellent acute toxic and antioxidant activities in Nauphoeta cinerea

Mentha arvensis is an herbaceous plant commonly known as peppermint or Japanese mint. This study investigated the toxic potential and repellent efficacy of M. arvensis essential oil (MaEO) at varying concentrations (15.625–250 mg/mL) in Nauphoeta cinerea, along with its impact on biochemical parameters in N. cinerea. The potential of the major compounds as a new analgesic target was investigated using molecular docking. The essential oil was analyzed by gas Chromatography–mass spectrometry (GC–MS) and the toxic potential, repellent property, and changes in lipid peroxidation (LPO) levels were evaluated as markers of oxidative stress. GC–MS results revealed that the main components were oxygenated monoterpenes such as menthol (71.31%), mentone (13.34%) and isomentone (5.35%). MaEO significantly reduced lipid peroxidation (LPO), the levels of non-protein thiols and iron(II) at the concentration of 125 mg/mL in N. cinerea. Furthermore, the major components, l-(−)-Menthol and menthone demonstrated high gastrointestinal absorption and high affinity with the target protein, suggesting possible links that contribute to the analgesic effect of MaEO.

Study to determine the efficacy and onset of Bonipar, a topical analgesic for the management of acute and chronic musculoskeletal pain

BackgroundOpioid abuse and mortality are ravaging American society, highlighting the need to find alternative effective analgesics with fewer side effects. FDA-approved topical analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs), are commonly used to treat musculoskeletal pain but can cause adverse effects. Natural compounds, including essential oils, are potential therapeutic alternatives for managing musculoskeletal pain. If these compounds can provide comparable analgesia to FDA-approved products, it will increase the available options for people with pain, improving quality of life with minimal morbidity and mortality. ObjectiveThis study assesses the effectiveness and onset of action of Bonipar, a topical analgesic formulated with camphor, methyl salicylate, and oils of coconut, eucalyptus, nutmeg, and rosemary, in managing musculoskeletal pain compared to 1.5 % diclofenac solution, an FDA-approved topical non-steroidal anti-inflammatory drug. MethodsOne hundred sixty-four adult patients with localized musculoskeletal pain were randomly assigned to twice-daily applications of either Bonipar or Diclofenac for one week. The primary outcome measure was a 50 % reduction in pain after one week. Secondary outcomes included the change in pain from baseline and onset of action, defined as the first reduction in pain by 20 %. ResultsAll patients completed the initial pain assessment to determine the onset of action. One-week data was available for 74 patients treated with diclofenac and 72 patients treated with Bonipar. Data for 18 patients were incomplete. The proportion of patients achieving a 50 % reduction in pain was statistically similar between the two groups. The success rates of achieving a 50 % pain reduction with Bonipar were found to be non-inferior to those treated with diclofenac. All follow-up time points showed roughly similar results between the groups. Regression models adjusted for age and sex revealed no significant effects on pain changes. Secondary analyses demonstrated no significant differences between the groups. DiscussionThe topical analgesic Bonipar demonstrates a comparable onset of action, with efficacy non-inferior to diclofenac in the management of musculoskeletal pain, while showing fewer adverse effects compared to diclofenac. These findings highlight the potential of Bonipar as a valuable alternative for the treatment of localized pain.

Bufalin alleviates inflammatory response and oxidative stress in experimental severe acute pancreatitis through activating Keap1-Nrf2/HO-1 and inhibiting NF-κB pathways

Severe acute pancreatitis (SAP) is a prevalent acute inflammatory disease that is clinically manifested by systemic inflammation dysregulation, resulting in a significantly elevated mortality rate. Bufalin has been verified to have potent pharmacological properties, including analgesic, anti-tumor and anti-inflammatory effects. However, it remains unclear whether bufalin inhibits SAP. Thus, we aim to explore the impact of bufalin in SAP rats and to evaluate the potential mechanisms of action. In addition to analyzing serum biochemistry and pancreatic tissue pathology, we elucidated its mechanisms of action through enzyme-linked immunosorbent assay (ELISA), immunohistochemical analysis, Western blot, and quantitative real-time PCR. The results demonstrated that bufalin dose-dependently reversed the elevation of serum Amylase (Amy) and Lipase (LPS) levels in SAP rats, alleviating pancreatic tissue pathological damage. Bufalin exhibited potent antioxidant effects by reducing malondialdehyde (MDA) levels, decreasing Superoxide dismutase (SOD) and glutathione(GSH) consumption, inhibiting the interaction of Keap1-Nrf2, and increasing HO-1 expression. Furthermore, bufalin inhibited TNF-α, IL-6, IL-1β, p-NF-κB-p65, p-IκBα, and NF-κB-p65 expression, while enhancing IκBα expression, ultimately confirming its anti-inflammatory effects on SAP. In summary, our findings suggest that bufalin exerts anti-inflammatory and antioxidant actions in NaT-SAP rats by inhibiting NF-κB and activating the Keap1-Nrf2/HO-1 pathway. This study represents the inaugural application of bufalin in NaT-induced SAP rats, indicating its potential as an effective therapeutic agent for SAP patients.

Conorphin-66 produces peripherally restricted antinociception via the kappa-opioid receptor with limited side effects

With the current unmet demand for effective pain relief, analgesics without major central adverse effects are highly appealing, such as peripherally restricted kappa-opioid receptor (KOR) agonists. In this study, Conorphin-66, an analog of the selective KOR peptide agonist Conorphin T, was pharmacologically characterized in a series of experiments, with CR845 serving as the reference compound. Firstly, in vitro functional assay indicated that Conorphin-66 selectively activates KOR and exhibits weak β-arrestin2 signaling bias (−1.54 versus −4.35 for CR845). Additionally, subcutaneous Conorphin-66 produced potent antinociception in mouse pain models with ED50 values ranged from 0.02 to 3.28 μmol/kg, including tail-flick test, post-operative pain, formalin pain, and acetic acid-induced visceral pain. Similarly, CR845 exert potent antinociception in mouse pain models ranged from 0.15 to 1.47 μmol/kg. Notably, antagonism studies revealed that the analgesic effects of Conorphin-66 were mainly mediated by the peripheral KOR. Furthermore, Conorphin-66 produced non-tolerance-forming antinociception over 8 days. Unlike CR845, subcutaneous Conorphin-66 did not promote the sedation, anxiogenic effects, depressive-like effects, but did exhibit diuretic activity. Further study showed that Conorphin-66 does not have apparent antipruritic effects in an acute itch model. Overall, Conorphin-66 emerges as a novel peripherally restricted KOR agonist that produced potent antinociception with reduced side effects.

Intrathecal Drug Delivery System in Prepontine Cistern for Patients with Intractable Craniofacial Cancer Pain: A Multicenter Retrospective Study.

Patients with craniofacial cancer frequently suffer from severe pain. The traditional intrathecal, oral, or intravenous analgesics could only provide insufficient pain relief with many side effects. Thus, a more effective analgesia approach is required. This study aimed to investigate the safety and efficacy of placing the catheter of an intrathecal morphine pump in the prepontine cistern for the treatment of craniofacial cancer pain. We performed a retrospective study of patients with primary or metastatic craniofacial cancer pain who received the catheter placement of an intrathecal morphine pump into the prepontine cistern in eleven medical centers from September 2019 to December 2023. Friedman test and pairwise signed-rank test were used to evaluate the difference in numeric rating scale (NRS) scores, the number of breakthrough pain episodes, dose of intrathecal morphine, and dose of systemic morphine equivalents (oral, patch, intravenous) from preoperative period to postoperative days 1, 7, and 30. P values were corrected for multiple comparisons using Bonferroni test. The study included 33 patients. The median (interquartile range [IQR]) of NRS scores at days 1, 7, and 30 postimplant were 2.0 (1.0-3.5), 2.0 (1.0-2.0), and 1.0 (1.0-2.0), respectively, which was significantly lower than that before surgery (median, 8.0; IQR, 7.0-10.0; all P < .001). Compared to baseline number/d of breakthrough pain episodes (median, 6.0; IQR, 4.5-10.0), there was a progressive decrease in the number/d of breakthrough pain episodes at day 1, day 7, and day 30 postimplant, and the median (IQR) were 1.0 (0.0-3.0), 2.0 (0.0-3.0), and 0.0 (0.0-1.2), respectively (all P < .001). Approximately 78.8% and 96.7% of patients reported pain relief >50% at days 1 and 30 postimplant, respectively. Compared with that at day 1 postimplant, the proportion of patients with a pain relief rate >75% at day 30 postimplant also increased with continued intrathecal treatment. Compared to the dose of baseline systemic morphine equivalents (median, 228 mg.d-1; IQR, 120-408 mg.d-1), the dose of systemic morphine equivalents reduced significantly from 0(0-120) mg.d-1 at day 1 postimplant (P = .001), to 0 (0-0) mg.d-1 at days 7 and 30 postimplant (both P < .001). Few patients reported perioperative adverse events, including nausea, constipation, hypotension, urinary retention, dry mouth, headache, and sedation. No severe adverse events occurred. Placing the catheter tip of an intrathecal morphine pump into the prepontine cistern could effectively relieve refractory craniofacial cancer pain with an extremely low total morphine dose requirement and few adverse events. This procedure could be considered in patients with severe refractory craniofacial cancer pain.

Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

Opioid-induced constipation is the most frequent and non-self-limiting adverse effect of opioid analgesia, reducing adherence and interfering with pain relief. This clinical trial aimed to clarify the preventive effect of naldemedine versus placebo for constipation in patients with cancer starting regularly dosed strong opioids therapy. This multicenter, double-blinded, randomized, placebo-controlled, confirmatory trial was conducted between July 2021 and May 2023 at four academic hospitals in Japan (ClinicalTrials.gov identifier: jRCTs031200397). Patients with cancer starting a first-time regularly dosed strong opioid for cancer pain and age 20+ years were included. Eligible patients were randomly assigned to the naldemedine (Symproic 0.2 mg) or placebo group in a 1:1 ratio for 14 days with protocol treatment. The primary end point was the proportion of patients with a Bowel Function Index (BFI) of <28.8 on day 14. The secondary end points included frequency of spontaneous bowel movements (SBM), quality of life (QOL), and frequency of opioid-induced nausea and vomiting (OINV). Of the 103 patients assessed for eligibility, 99 received either naldemedine (n = 49) or placebo (n = 50). A BFI of <28.8 on day 14 was significantly more likely to occur in the naldemedine group (64.6%; 95% CI, 51.1 to 78.1) versus placebo (17.0%; 95% CI, 6.3 to 27.8), and the difference between groups was 47.6% (95% CI, 30.3 to 64.8; P < .0001). The frequency of SBM, QOL, and the severity of OINV were nominally significant in the naldemedine group than in the control group. Naldemedine prevented constipation and improved constipation-related QOL, with possible preventive effect on OINV in patients with cancer starting regularly dosed opioids therapy.

Investigating combined acupuncture and transcranial direct current stimulation in patients with poststroke shoulder pain from China: protocol for a randomised controlled trial

IntroductionPoststroke shoulder pain is a common complication that severely affects the recovery of upper limb motor function. Acupuncture has positive analgesic effects in treating poststroke shoulder pain, and studies have...

The Role of the Mu Opioid Receptors of the Medial Prefrontal Cortex in the Modulation of Analgesia Induced by Acute Restraint Stress in Male Mice

Mu opioid receptors (MORs) represent a vital mechanism related to the modulation of stress-induced analgesia (SIA). Previous studies have reported on the gamma-aminobutyric acid (GABA)ergic “disinhibition” mechanisms of MORs on the descending pain modulatory pathway of SIA induced in the midbrain. However, the role of the MORs expressed in the medial prefrontal cortex (mPFC), one of the main cortical areas participating in pain modulation, in SIA remains completely unknown. In this study, we investigated the contributions of MORs expressed on glutamatergic (MORGlut) and GABAergic (MORGABA) neurons of the medial prefrontal cortex (mPFC), as well as the functional role and activity of neurons projecting from the mPFC to the periaqueductal gray (PAG) region, in male mice. We achieved this through a combination of hot-plate tests, c-fos staining, and 1 h acute restraint stress exposure tests. The results showed that our acute restraint stress protocol produced mPFC MOR-dependent SIA effects. In particular, MORGABA was found to play a major role in modulating the effects of SIA, whereas MORGlut seemed to be unconnected to the process. We also found that mPFC–PAG projections were efficiently activated and played key roles in the effects of SIA, and their activation was mediated by MORGABA to a large extent. These results indicated that the activation of mPFC MORGABA due to restraint stress was able to activate mPFC–PAG projections in a potential “disinhibition” pathway that produced analgesic effects. These findings provide a potential theoretical basis for pain treatment or drug screening targeting the mPFC.

Harnessing the therapeutic effects of nature for chronic Pain: A role for immersive virtual reality? A narrative review.

There is a growing interest in the relationship between nature and pain relief. Evidence from environmental psychology, neuroscience and physiology-based studies point towards analgesic effects of nature being mediated through various cognitive, affective and/or autonomic factors. Being able to harness these therapeutic effects using immersive virtual reality (VR) could help to optimize and improve accessibility of nature-based environments as part of chronic pain management plans. In this narrative review, we present evidence supporting a new theoretical framework for nature-based analgesia and suggest ways for applying this through immersive VR. We provide an overview of the evidence on (1) the therapeutic effects of nature on pain, (2) environmental psychology theory that underpins the health benefits of nature, (3) key mechanistic evidence from nature neuroimaging and physiology-based studies, (4) previous studies that have used VR-based nature in pain research and (5) how to design effective VR interventions that can be used to integrate nature into immersive 360 environments. We have demonstrated how environmental psychology, neuroscience and physiology-based research can be used to form a novel theoretical framework for nature-based analgesia. Using this framework, we identify how key aspects of nature can act as analgesic and how this can be harnessed using immersive VR. Through developing this theoretical framework, we have provided a foundation on which to guide future experimental and clinical studies as well as helping to improve the accessibility of nature for chronic pain patients through immersive VR technologies. This review article summarizes key multidisciplinary evidence to help understand how nature exerts beneficial effects on pain processing. The use of this theoretical framework alongside advances in immersive VR technologies provides a springboard for future research and can be used to help develop new nature-based therapeutics using VR.

Propofol versus Dexmedetomidine for Sedation of Cancer Patients Undergoing Endoscopic Retrograde Cholangiopancreatography: Randomized Single-Blinded Controlled Study

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a primary diagnostic and therapeutic option for pancreaticobiliary pathologies. Objectives: This study aimed to investigate the efficacy and safety of dexmedetomidine versus propofol during ERCP in cancer patients. Methods: This randomized controlled single-blinded trial was conducted with 202 cancer patients aged 21 to 60 years, of both sexes, with a body mass index of 18.5 to 30 kg/m2, and classified as American Society of Anesthesiologists (ASA) class II - III, who were undergoing ERCP. The patients were randomly assigned to two equal groups. The Propofol Group (n = 101) received a loading dose of propofol (1 - 2 mg/kg over 30 seconds) followed by an infusion (0.05 - 0.1 mg/kg/hour). The Dexmedetomidine Group (n = 101) received a loading dose of dexmedetomidine (1 μg/kg over 10 minutes) followed by an infusion (0.2 - 0.7 μg/kg/hour). The maintenance dose was adjusted during the procedure based on vital signs, Bispectral Index (BIS), and oxygen saturation. Results: The Dexmedetomidine group showed a significantly lower incidence of intra-procedural hypoxemic events (14.9% vs. 26.7%, P = 0.037) and a comparable incidence of hypotension (17.8% vs. 13.9%, P = 0.441). Dexmedetomidine also demonstrated significantly lower intraoperative pain scores according to the Facial Pain Score (P &lt; 0.05), significantly lower postoperative Visual Analog Scale (VAS) scores (P &lt; 0.05), and a lower frequency of postoperative nausea and vomiting (PONV) compared to the Propofol group. Additionally, there was a significantly higher frequency of endoscopist satisfaction in the Dexmedetomidine group compared to the Propofol group (P &lt; 0.05). Conclusions: Dexmedetomidine can be used as a safe and effective alternative to propofol for deep sedation of cancer patients undergoing ERCP. It is associated with a lower incidence of hypoxemic events, effective intraoperative sedation, quicker recovery, and superior analgesic effects both intraoperatively and postoperatively compared to propofol.

Optimizing Nav1.7-Targeted Analgesics: Revealing Off-Target Effects of Spider Venom-Derived Peptide Toxins and Engineering Strategies for Improvement.

The inhibition of Nav1.7 is a promising strategy for the development of analgesic treatments. Spider venom-derived peptide toxins are recognized as significant sources of Nav1.7 inhibitors. However, their development has been impeded by limited selectivity. In this study, eight peptide toxins from three distinct spider venom Nav channel families demonstrated robust inhibition of hNav1.7, rKv4.2, and rKv4.3 (rKv4.2/4.3) currents, exhibiting a similar mode of action. The analysis of structure and function relationship revealed a significant overlap in the pharmacophore responsible for inhibiting hNav1.7 and rKv4.2 by HNTX-III, although Lys25 seems to play a more pivotal role in the inhibition of rKv4.2/4.3. Pharmacophore-guided rational design is employed for the development of an mGpTx1 analogue, mGpTx1-SA, which retains its inhibition of hNav1.7 while significantly reducing its inhibition of rKv4.2/4.3 and eliminating cardiotoxicity. Moreover, mGpTx1-SA demonstrates potent analgesic effects in both inflammatory and neuropathic pain models, accompanied by an improved in vivo safety profile. The results suggest that off-target inhibition of rKv4.2/4.3 by specific spider peptide toxins targeting hNav1.7 may arise from a conserved binding motif. This insight promises to facilitate the design of hNav1.7-specific analgesics, aimed at minimizing rKv4.2/4.3 inhibition and associated toxicity, thereby enhancing their suitability for therapeutic applications.

Analgesic Effect of Human Placenta Hydrolysate on CFA-Induced Inflammatory Pain in Mice

To evaluate the efficacy of human placenta hydrolysate (HPH) in a mice model of CFA-induced inflammatory pain. TNF-α, IL-1β, and IL-6 are key pro-inflammatory cytokine factors for relieving inflammatory pain. Therefore, this study investigates whether HPH suppresses CFA-induced pain and attenuates the inflammatory process by regulating cytokines. In addition, the relationship between neuropathic pain and HPH was established by staining GFAP and Iba-1 in mice spinal cord tissues. This study was conducted for a total of day 28, and inflammatory pain was induced in mice by injecting CFA into the right paw at day 0 and day 14, respectively. 100 μL of 20% glucose and polydeoxyribonucleotide (PDRN) and 100, 200, and 300 μL of HPH were administered intraperitoneally twice a week. In the CFA-induced group, cold and mechanical allodynia and pro-inflammatory cytokine factors in the spinal cord and plantar tissue were significantly increased. The five groups of drugs evenly reduced pain and gene expression of inflammatory factors, and particularly excellent effects were confirmed in the HPH 200 and 300 groups. Meanwhile, the expression of GFAP and Iba-1 in the spinal cord was increased by CFA administration but decreased by HPH administration, which was confirmed to suppress damage to peripheral ganglia. The present study suggests that HPH attenuates CFA-induced inflammatory pain through inhibition of pro-inflammatory cytokine factors and protection of peripheral nerves.