A randomized controlled trial of rectal versus intramuscular diclofenac for post-operative analgesia after open myomectomy.

AIM: To determine the efficacy and safety of rectal versus intramuscularly administered Diclofenac in reducing post-operative pain in the first 24 h after open-myomectomy. METHODS: A single blind, placebo controlled randomized trial consisting of 90 consenting women that had open-abdominal-myomectomy. They were randomized into two-groups (rectal-group and intramuscular-group) of 45 women (1:1 ratio). Rectal-group received 75 mg of Diclofenac suppository 12 hourly for 24 h and placebo (3 ml of intramuscular injection-water) 12hourly for 24 h while intramuscular-group received intramuscular Diclofenac 75 mg 12 hourly for 24 h and placebo (Anusol suppository) 12 hourly for 24 h. Both groups received intramuscular Pentazocine 30 mg 6 hourly for 24 h as primary analgesic after myomectomy. Pain was assessed using a Ten-Point Visual-Analogue-Scale. Participants' satisfaction of the mode of the pain relief was assessed using the Likert-scale after 24 h. The primary outcome was the pain score using the visual-analogue-scale. The secondary outcome-measures were participants' satisfaction after 24 h of administration of the drugs, the need and frequency of rescue-analgesia and maternal-side-effects. RESULT: The baseline socio-demographic characteristics were similar in both groups. There was no statistically significant difference between both groups in pain assessment at 1 h post-myomectomy (p-value > 0.05). However, the pain assessments at 6, 12, 18 and 24 h post-myomectomy were statistically significant with more pain in intramuscular-group when compared to rectal-group. Majority of participants in rectal-group were both very satisfied (35.6 %) and satisfied (55.6 %) when compared to intramuscular-group (11.1 %) and (31,1%) respectively (p-value < 0.05). Also majority of the participants in intramuscular-group were dissatisfied (17.8 %) with none of the participant showing any form of dissatisfaction (p-value < 0.05). Majority of the participant in rectal-group had no drug side effects when compared with intramuscular-group. Epigastric discomfort was commoner in rectal-group while drowsiness was commoner in intramuscular-group. CONCLUSION: Rectal Diclofenac with intramuscular Pentazocine is significantly associated with better effectiveness in pain reduction and maternal satisfaction when compared with intramuscular Diclofenac and intramuscular Pentazocine following open-myomectomy. While epigastric discomfort was the commonest side-effect in rectal-group, drowsiness was commoner in intramuscular-group. TRIAL REGISTRATION: Pan-African-clinical-trial-registry (PACTR); PACTR202206556144219.

Intra-articular injection versus interscalene brachial plexus block for acute-phase postoperative pain management after arthroscopic shoulder surgery.

BACKGROUND: The minimally invasive approach of arthroscopic shoulder surgery is beneficial; however, for optimal outcomes, perioperative pain management is essential. This cross-sectional study aimed to examine the analgesic effectiveness of intra-articular injection (IA) versus interscalene brachial plexus block (ISPB) among patients treated with arthroscopic shoulder surgeries. METHODS: We reviewed 100 consecutive patients who underwent shoulder arthroscopic surgery, of whom 50 each underwent IA (February 2019─January 2020; IA group) and ISPB (October 2018─July 2019; ISPB group). The primary outcome was the postoperative pain score measured using a Wong-Baker FACES Pain Rating Scale preoperatively and at 2, 6, 12, 24, and 48 h postoperatively. We performed multiple regression analysis to examine whether IA/ISPB selection is associated with acute-phase postoperative pain and adjusted for intra-articular injection, interscalene brachial plexus block, postoperative pain management, arthroscopic shoulder surgery, IA with 10 mg of morphine previously reported prognostic factors for postoperative pain (e.g., surgical procedures, operative time, older age, and preoperative pain). Furthermore, we examined induction time, total pentazocine dosage, and total postoperative nausea and vomiting (PONV) events. RESULTS: There were no significant differences between the IA and ISPB groups in perioperative pain control during the acute-phase periods (p = 0.12, repeated analysis of variance). The difference in anesthesia method was not a prognostic factor for acute-phase postoperative pain (p = 0.11). The IA group (15.06 ± 4.00 min) had a significantly shorter mean anesthesia induction time than the ISPB group (29.23 ± 9.22 min) (p = 0.0001). There was no significant between-group difference in the total pentazocine dosage during the first 7 days (p = 0.3934) postoperatively. PONV was observed in eight (17.0%) and two (4.2%) patients in the IA and ISPB groups, respectively. There was no significant between-group difference in the PONV incidence (p = 0.1582). CONCLUSIONS: There was no significant difference in acute-phase postoperative pain management between the IA and ISPB groups. The induction time was significantly shorter in IA. IRB: Approval number: UOEHCRB20-078, IRB approval date: September 9th, 2020; study duration: October 2018 to January 2020.

Sigma-1 receptor agonist, (+)-pentazocine, is neuroprotective in a Brown Norway rat microbead model of glaucoma.

PURPOSE: Glaucoma is a worldwide leading cause of irreversible blindness. Standard treatments lower intraocular pressure (IOP). Novel treatments to prevent optic nerve (ON) degeneration are needed. Here, we investigate the hypothesis that sigma-1 receptor (S1R) agonist (+)-pentazocine (PTZ) is neuroprotective in a Brown Norway (BN) rat, microbead model of glaucoma. METHODS: BN rats (9-11 weeks, male and female) were treated by intraperitoneal injection, 3 times per week with (+)-PTZ (2 mg/kg) or vehicle (VEH) alone. Treatment started 1 week prior to intraocular injection of polystyrene microbeads to elevate IOP. IOP was measured 2-3 times per week. Five weeks post microbead injection, rats were euthanized. ONs were removed, then fixed and processed for 63x oil, light microscope imaging of toluidine blue stained ON cross sections. To facilitate comparison of ON morphology from VEH and (+)-PTZ treated rats with similar ocular hypertensive insults, rats were assigned to low (IOP ≤15.8 mmHg), moderate (15.8 < IOP <28.0 mmHg), and high (IOP ≥28.0 mmHg) groups based on average IOP in the microbead injected eye. Axon numbers, axon density, axonal and glial areas, axon loss, and axon size distributions of naïve, bead, and contralateral ONs were assessed using QuPath program for automated image analysis. RESULTS: (+)-PTZ treatment of BN rats protected ONs from damage caused by moderate IOP elevation. Treatment with (+)-PTZ significantly reduced axon loss and glial areas, and increased axon density and axonal areas compared to ONs from VEH treated rats with moderate IOP. (+)-PTZ-mediated neuroprotection was independent of IOP lowering effects. At average IOP ≥28.0 mmHg, (+)-PTZ treatment did not provide measurable neuroprotection. ONs from contralateral eyes exhibited subtle, complex changes in response to conditions in the bead eyes. CONCLUSIONS: S1R agonist (+)-PTZ shows promise as a neuroprotective treatment for glaucoma. Future studies to understand the complex molecular mechanisms by which (+)-PTZ provides this neuroprotection are needed.

Retinal Photoreceptor Protection in an AMD-Related Mouse Model by Selective Sigma-1 or Sigma-2 Receptor Modulation.

The structurally and genetically distinct sigma-1 receptor (S1R) and sigma-2 receptor (S2R) comprise a unique class of drug binding sites. Their alleles are associated with human diseases involving neuronal systems, such as age-related macular degeneration (AMD) characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. Previous studies have suggested neuroprotective benefits for the brain and retina from pharmacological modulation of S1R and/or S2R. However, the effect of such modulation on AMD pathology remains underexplored. Here, we evaluated S1R- or S2R-selective modulation in an AMD-related model of Abca4-/-Rdh8-/- mice with a disrupted visual cycle that predisposes RPE and photoreceptors to illumination-induced damage. For S1R modulation, we used (+)-pentazocine, which is a high-affinity S1R-selective drug. For S2R modulation, we chose CM398, a high-affinity and highly S2R-selective ligand with drug-like properties. Abca4-/-Rdh8-/- mice received a single i.p. injection of (+)-pentazocine or CM398 or vehicle 30 min before illumination. Pretreatment with (+)-pentazocine improved electroretinogram a- and b-waves compared to that with vehicle. Consistently, in another AMD-related mouse model induced by tail-vein injected NaIO3, S1R genetic ablation aggravated photoreceptor loss. In Abca4-/-Rdh8-/- mice, pretreatment with CM398 appeared to partially avert illumination-induced photoreceptor loss and autofluorescent granule formation that signals RPE damage, as revealed by optical coherence tomography. Thus, this study using AMD-related models provides evidence of photoreceptor protection afforded by selective modulation of S1R or S2R.

Pharmacokinetic/Pharmacodynamic Modeling and Simulation of the Analgesic Effects of Pentazocine Using Perioperative Real-World Data.

Pentazocine (PTZ) is a widely used drug for postoperative pain. It should be administered at appropriate dosing intervals not only because of its morphine-like side effects but also because frequent inappropriate dosing can lead to dependence. Although perioperative patients reportedly have nonnegligible effects on placebo drugs and postoperative wound healing, no pharmacokinetic (PK)/pharmacodynamic (PD) model has been established and simulated using real-world data for the perioperative period. This study aimed to perform PTZ modeling and simulation and to establish an indicator of the timing of drug efficacy evaluation in clinical practice. Participants were in-hospital orthopedic surgery patients who received 15 mg of PTZ within 48 h postoperatively. Pain severity was assessed using the numerical rating scale (NRS). A two-compartment model was selected for the population PK model and an indirect response model for the PK/PD model. Using these models, a virtual population of 1000 patients with Painbase NRS of 5 and 6 and body weights of 40, 80, and 120 kg were treated with single and multiple PTZ administrations (4, 8, and 24 h apart) of 15 mg. Simulation results indicate that its analgesic efficacy should be evaluated within 1 h after administration of 15 mg of PTZ. Additional doses should be considered every 8-12 h in postoperative patients with Painbase NRS of 5 weighing 40-80 kg. Simulation using the PK/PD model developed in this study may provide useful information for determining the analgesic effects and timing of the dosing interval after PTZ administration in perioperative patients.

Effect of scalp infiltration with bupivacaine on analgesic requirement following elective craniotomy.

Background: Postcraniotomy pain and perioperative assessment of patients' neurological function are some of the issues associated with craniotomy surgeries. Cost-effective pain control will result in good clinical outcome, decrease the length of hospital stay, and reduce total cost. Infiltration anesthesia is a recognized modality of cost-effective pain control. Objective: The study determined the effect of scalp infiltration with 0.25% plain bupivacaine on pain control following craniotomy. Methods: A prospective randomized study recruited 50 consenting patients scheduled for craniotomy under general anesthesia into two study groups. All patients received routine general anesthesia as per local protocol and received scalp infiltration after skin closure. Group A received 20 ml of 0.25% plain bupivacaine, while Group B received 20 ml normal saline. Pain scores were assessed using the Visual Analog Scale (VAS) on admission into the intensive care unit (ICU) then at 4, 8, 12, 16, 20, 24, and 48 h after surgery. The interval between the end of surgery and the first request for analgesia, 4 hourly intervals pentazocine and the cumulative doses of pentazocine given for postoperative pain relief. Results: The presenting VAS at the ICU and total postoperative analgesic consumption at 48 h were significantly lower in the bupivacaine group compared to the saline group. In addition, the increase in time to the first analgesic request was statistically significant between the two. There was a trend toward the reduced incidence of sedation and postoperative nausea and vomiting in the bupivacaine group compared to the saline group. Conclusions: Postoperative scalp infiltration with plain 0.25% bupivacaine reduced pain intensity and opioid analgesic consumption among the studied patients. Resultantly, it can be regarded as an effective technique of pain management after an elective craniotomy.

Résumé Contexte: La douleur post-craniotomie et l'évaluation périopératoire de la fonction neurologique des patients sont quelques-uns des problèmes associés aux chirurgies de craniotomie. Un contrôle de la douleur rentable se traduira par de bons résultats cliniques, réduira la durée du séjour à l'hôpital et réduira le coût total. L'anesthésie par infiltration est une modalité reconnue de contrôle de la douleur rentable. Objectif: L'étude a déterminé l'effet de l'infiltration du cuir chevelu avec de la bupivacaïne simple à 0,25 % sur le contrôle de la douleur après une craniotomie. Méthodes: Une étude prospective randomisée a recruté 50 patients consentants devant subir une craniotomie sous anesthésie générale en deux groupes d'étude. Tous les patients ont reçu une anesthésie générale de routine selon le protocole local et ont reçu une infiltration du cuir chevelu après la fermeture de la peau. Le groupe A a reçu 20 ml de bupivacaïne simple à 0,25%, tandis que le groupe B a reçu 20 ml de solution saline normale. Les scores de douleur ont été évalués à l'aide de l'échelle visuelle analogique (EVA) à l'admission en unité de soins intensifs (USI) puis à 4, 8, 12, 16, 20, 24 et 48 h après la chirurgie. L'intervalle entre la fin de la chirurgie et la première demande d'analgésie, les intervalles de quatre heures de Pentazocine ainsi que les doses cumulées de Pentazocine administrées pour le soulagement de la douleur postopératoire ont été enregistrés. Résultats: L'EVA présentée à l'USI et la consommation totale d'analgésique postopératoire à 48 h étaient significativement plus faibles dans le groupe bupivacaïne par rapport au groupe solution saline. De plus, l'augmentation du délai jusqu'à la première demande d'analgésique était statistiquement significative entre les deux. Il y avait une tendance à la réduction de l'incidence de la sédation et des nausées et vomissements postopératoires dans le groupe bupivacaïne par rapport au groupe solution saline. Conclusions: L'infiltration postopératoire du cuir chevelu avec de la bupivacaïne simple à 0,25 % a réduit l'intensité de la douleur et la consommation d'analgésiques opioïdes chez les patients étudiés. Par conséquent, elle peut être considérée comme une technique efficace de gestion de la douleur après une craniotomie élective. Mots-clés: Analgésie, bupivacaïne, craniotomie, infiltration du cuir chevelu.

Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats.

Background: Pentazocine produces a wide variety of actions in the treatment of perioperative analgesia. Neostigmine is a cholinesterase inhibitor used to antagonize the residual effects of muscle relaxants and also produces an analgesic effect. Objectives: To investigate the analgesic effects of intrathecally injected pentazocine and neostigmine and their interaction. Methods: Sprague-Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model. Pentazocine (3, 10, 30, and 100 µg), neostigmine (0.3, 1, 3, and 10 µg) or a pentazocine-neostigmine mixture were separately injected to evaluate their antinociceptive effects alone on the treatment groups. The corresponding control group received an intrathecal injection containing the same volume of saline. The formalin pain test, or the plantar incision pain behavior test were performed 30 minutes later. Isobolographic analysis was used to evaluate the interaction between pentazocine and neostigmine. Intrathecally administered selective mu-opioid receptor antagonist CTAP, selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), nonselective opioid receptor antagonist naloxone, and muscarinic acetylcholine receptor antagonist atropine were also used to test the possible interaction mechanism. These antagonists were used 30 minutes before the pentazocine and neostigmine mixtures which were intrathecally injected. Results: Intrathecally administered pentazocine (3, 10, 30, and 100 µg) and neostigmine (0.3, 1, 3, and 10 µg) alone had a marked dose-related impact on suppressing the biphasic responses in the formalin test. Pentazocine (3, 10, 30, and 100 µg) and neostigmine (0.3, 1, 3, and 10 µg) alone attenuated the mechanical allodynia in a plantar incision model in a dose-dependent manner. Isobolographic analysis revealed that the mixture of intrathecal pentazocine and neostigmine synergistically decreased both phase I and II activity in the formalin test and mechanical allodynia in the plantar incision model. Pretreatment of intrathecally administered nor-BNI, naloxone, atropine, but not CTAP, antagonized the analgesic effect of the pentazocine-neostigmine mixture. Conclusions: All of these results suggest that the combined application of pentazocine and neostigmine is an effective way to relieve pain from formalin and acute incision mechanical allodynia. The synergistic effect between pentazocine and neostigmine is mostly attributed to the kappa-opioid receptor and the cholinergic receptor in the spinal cord.

Pentazocine with rectal diclofenac versus pentazocine alone for pain relief following caesarean delivery in Enugu, Nigeria: A randomized controlled trial.

OBJECTIVE: To measure postoperative pain relief following the use of rectal diclofenac combined with intramuscular pentazocine compared with intramuscular pentazocine alone in patients undergoing a caesarean delivery. METHODS: This single-blind randomized controlled trial enrolled pregnant women that had a caesarean section at the Enugu State University of Science and Technology Teaching Hospital, Enugu, Nigeria. Study participants were randomized to receive either 100 mg of rectal diclofenac given every 12 h plus 30 mg of intramuscular pentazocine given every 6 h (group A) or 60 mg of intramuscular pentazocine given every 6 h (group B). The primary outcome was the level of pain as measured using a visual analogue scale. The secondary outcomes were the level of satisfaction with pain relief and need for rescue analgesia. RESULTS: A total of 200 participants were randomized equally into the two groups. Participants in group A had significantly better pain control and satisfaction over the 48 h after surgery compared with group B. Significantly more of group B required rescue analgesia for breakthrough pain compared with group A. CONCLUSION: Rectal diclofenac combined with intramuscular pentazocine was significantly better at controlling pain compared with pentazocine alone in the first 48 h following caesarean section.Trial registration number: PACTR202107706925314 at www.pactr.org on 28 July 2021.

Intracellular dynamics of the Sigma-1 receptor observed with super-resolution imaging microscopy.

Sigma-1 receptor (Sig1R) is an endoplasmic reticulum (ER)-related membrane protein, that forms heteromers with other cellular proteins. As the mechanism of action of this chaperone protein remains unclear, the aim of the present study was to detect and analyze the intracellular dynamics of Sig1R in live cells using super-resolution imaging microscopy. For that, the Sig1R-yellow fluorescent protein conjugate (Sig1R-YFP) together with fluorescent markers of cell organelles were transfected into human ovarian adenocarcinoma (SK-OV-3) cells with BacMam technology. Sig1R-YFP was found to be located mainly in the nuclear envelope and in both tubular and vesicular structures of the ER but was not detected in the plasma membrane, even after activation of Sig1R with agonists. The super-resolution radial fluctuations approach (SRRF) performed with a highly inclined and laminated optical sheet (HILO) fluorescence microscope indicated substantial overlap of Sig1R-YFP spots with KDEL-mRFP, slight overlap with pmKate2-mito and no overlap with the markers of endosomes, peroxisomes, lysosomes, or caveolae. Activation of Sig1R with (+)-pentazocine caused a time-dependent decrease in the overlap between Sig1R-YFP and KDEL-mRFP, indicating that the activation of Sig1R decreases its colocalization with the marker of vesicular ER and does not cause comprehensive translocations of Sig1R in cells.

The analgesic effect of the intravenous administration of acetaminophen for pediatric laparoscopic appendectomy: A comparison of scheduled and on-demand procedures.

PURPOSE: The intravenous administration of acetaminophen (IAA) has become standard postoperative analgesic management for pediatric surgery. However, the most effective methods of IAA for postoperative acute appendicitis are unclear. We evaluated the analgesic efficacy of scheduled IAA vs on-demand IAA for postoperative acute appendicitis. METHODS: Ninety-four patients who underwent laparoscopic appendectomy in our institution between January 2017 and December 2020 were enrolled. The patients were divided into two groups based on the postoperative pain control protocols. The scheduled IAA group (SA group, n = 42) was managed by scheduled IAA and additional on-demand use of pentazocine as rescue therapy. The on-demand IAA group (ODA group, n = 52) was managed by on-demand IAA as the first choice, with pentazocine as the second choice for pain control. The patients' background characteristics, operative results and postoperative outcomes were reviewed. RESULTS: The number of times pain complaints were made per patient per day (NPPD) on postoperative days (POD) 1 and 2 was significantly lower in the SA group than in the ODA group (POD 1; 1.12 ± 1.21 vs 2.62 ± 1.89, p < 0.01; POD 2; 0.45 ± 0.86 vs. 1.31 ± 1.69, p < 0.01). According to pathological findings, NPPD was lower in the SA group than in the ODA group for both phlegmonous appendicitis (0.71 ± 1.01 vs. 2.10 ± 2.13, P < .05) and gangrenous appendicitis (1.33 ± 1.50 vs 2.94 ± 1.68, P < .01). On POD 2, the incidence of gangrenous appendicitis was significantly lower in the SA group than in the ODA group (0.57 ± 0.93 vs 1.78 ± 1.86, P < .01). CONCLUSIONS: Scheduled IAA may have favorable efficacy for postoperative pain control after emergency surgery for acute appendicitis in pediatric patients.

Urinalysis based assessment of compliance and drug use patterns in patients prescribed tramadol: A cross-sectional study from a tertiary care centre.

BACKGROUND: Strict adherence to pharmacological dosage regimens is a prerequisite to the success of most treatments, particularly for patients in drug abuse programs. The compliance of tramadol, an atypical non-scheduled narcotic analgesic, using objective method has not been adequately studied in an Indian setting. AIM: To evaluate the compliance and pattern of drug use among opioid-dependent subjects prescribed tramadol based on urinalysis. METHOD: Fifty male opioid-dependent patients (ICD 10), seeking treatment at a tertiary de-addiction treatment centre of North India on tramadol prescription for atleast past four weeks were included. Self-reported substance use was recorded using semi-structured proforma. Ten ml of urine was collected for the assessment of compliance of tramadol of other substance use (morphine, buprenorphine, dextropropoxyphene, pentazocine, cannabis, benzodiazepines, pheniramine). All these drugs were analyzed using the immunoassay-based Cassette test and Gas Chromatography in human urine. RESULT: Mean age of the participants was 42.8 years and the mean duration of opioid use was 15.9years. The urine specimen of all subjects tested positive for tramadol. Urinalysis revealed benzodiazepines, cannabis, and pheniramine to be the most common substances of use in this population. It was seen that agreement of self-reporting and urine test results was good for morphine (κ = 0.558) and cannabis (κ = 0.312) and was poor for buprenorphine, pentazocine, and pheniramine. CONCLUSION: The study demonstrates the continued use of several illicit or non-prescribed medications in a medication-assisted opioid treatment population. The results affirm the reliability of urinalysis as an adjunct for testing compliance in such a population.

Split-thickness skin grafting in the management of cutaneous sequelae of intramuscular pentazocine injections: a novel approach.

INTRODUCTION: Pentazocine, a synthetic opioid with partial agonist and antagonist activity administered by parenteral injection, was used clinically in the 1970s. Dermatologic complications at injection sites were reported soon after its introduction. These complications are thought to be underreported. Many well-documented cases describe the development of fibrosis and calcinosis at the site of parenteral pentazocine injections, but few reports document management or successful treatment of the long-term sequelae of these manifestations. CASE REPORT: The successful use of STSG for the treatment of chronic nonhealing ulcers secondary to pentazocine-induced cutaneous fibrosis in a 78-year-old male is presented. In the early 1970s, he was started on 3-times-daily intramuscular pentazocine injections to treat pain secondary to ulcerative colitis. He injected himself in the proximal thighs and buttocks for a period of approximately 10 years. He gradually developed severe soft tissue calcifications of both buttocks and anterior thighs. In the mid-to-late 1980s, the pentazocine injections were discontinued. The diffuse sclerosis and disfiguring fibrosis remained. CONCLUSIONS: This case underscores the lasting effects of pentazocine-induced cutaneous sclerosis and fibrosis, with cutaneous complications manifesting in this patient even decades after use. It also highlights the novel use of STSG as a treatment strategy for these cutaneous complications.

Pentazocine versus tramadol-paracetamol combination as analgesia in labor: A randomized controlled trial

Objectives: Labor should be a satisfactory experience and effective pain management should be employed as recommended by the American Congress of Obstetricians and Gynaecologists. In developing countries, pain management in labor is still a big challenge and the search for the ultimate labor analgesia is still ongoing. The objectives of the study were to determine whether the synergistic analgesic effect of the combination of tramadol and paracetamol will produce analgesia comparable to pentazocine with a better side effect profile. Material and Methods: This was a randomized controlled, double-blinded trial of tramadol-paracetamol combination versus pentazocine as labor analgesia and was carried out at the University of Abuja Teaching Hospital, Abuja, between June 2018 and March 2019. A total of 218 eligible parturients recruited at term, were counseled on labor analgesia, its benefits, and the options made available to them and educated on the pain scoring system. Parturients were allocated into two groups using computer-generated numbers with the WINPEPI software. Group A was given tramadol-paracetamol combination, while Group B received pentazocine, both at standard doses. Hourly pain scores, APGAR scores, labor duration, patients' satisfaction, and side effects were collated. The level of significance was set at <0.05. Results: Tramadol-paracetamol was administered to 109 (50.9%) while pentazocine was administered to105 (49.1%) of the study participants. The mean age in the tramadol-paracetamol group was 29.6 ± 4.8 years, and in the pentazocine group, it was 28.8 ± 4.5 years. The difference in pain scores on the visual analog scale was statistically significant at the 3rd and 4th h (P = 0.02 and 0.004), but not significant in the 1st and 2nd h (P = 0.05 and 0.22) in the two groups. Overall, the average pain score in the tramadol-paracetamol group was significantly higher compared to the pentazocine group (5.27 ± 1.86 vs. 4.72 ± 1.54; P = 0.02). The 1st and 5th min APGAR scores (P = 0.44 and 0.67, respectively) of neonates in the tramadol-paracetamol and pentazocine groups were comparable. Nausea and drowsiness occurred more frequently in the pentazocine group at P-values of 0.047 and 0.0015, respectively. There was no statistically significant difference in the duration of labor between the tramadol-paracetamol and pentazocine groups. not statistically significant, a higher proportion of parturients in the pentazocine group was satisfied compared with the tramadol-paracetamol group (71.4% vs. 63.3%; P = 0.13).Conclusion: This study showed that intravenous pentazocine provides better pain relief in labor, but the tramadol-paracetamol combination has fewer side effects

The efficacy of pentazocine + diclofenac versus paracetamol + diclofenac for post- caesarean section analgesia.

BACKGROUND: The most common major obstetric procedure is caesarean section (CS) and one of the greatest concerns for women after CS is to have optimal pain relief. AIM: This study aims to compare the efficacy of pentazocine + diclofenac and paracetamol + diclofenac on post-operative analgesia after CS. METHODOLOGY: This was a single-blind, randomised trial. Pregnant women that had CS were randomized into two groups. Group A received intramuscular pentazocine + rectal diclofenac postoperatively. Group B received intramuscular paracetamol + rectal diclofenac postoperatively. Post-operative pain was assessed by numeric rating scale at 1 h after the surgery, at 6 h, 12 h and 24 h. The result obtained was analysed using SPSS Version 22 and P < 0.05 was considered statistically significant. RESULTS: The median pain scores in both groups ranged from 2 to 3 across all periods of assessment. The pain relief was slightly better in the pentazocine + diclofenac group with no significant difference in the pain score between the two groups at all periods of assessment. The satisfaction level was good in 66.3% and 69.5% of the participants in the pentazocine + diclofenac and paracetamol + diclofenac group respectively but the difference was not statistically significant (χ2 = 4.14, P = 0. 12). Nausea, vomiting and drowsiness were significantly more in the pentazocine + diclofenac combination (P < 0.001). CONCLUSION: Both combination of analgesics provided adequate analgesia but pentazocine + diclofenac combination had better pain relief but was more associated with side effects.

Comparative study of dezocine, pentazocine and tapentadol on antinociception and physical dependence.

AIMS: Dezocine and pentazocine, widely prescribed in China for postoperative pain, were initially considered as mixed agonist/antagonist targeting µ-opioid receptors (MORs) and κ-opioid receptors (KORs). However, dezocine has been revealed to alleviate chronic neuropathic pain through MOR activation and norepinephrine reuptake inhibition (NRI). This study investigated dezocine- and pentazocine-induced antinociception and physical dependence development, compared to the typical MOR-NRI opioid tapentadol. MAIN METHODS: Calcium mobilization assay was conducted to assess the potency of the drugs while hot-plate test was performed to compare the antinociception. Physical dependence development was compared with morphine. KEY FINDINGS: Treatment with dezocine, pentazocine and tapentadol stimulated calcium mobilization in HEK293 cells stably expressed MORs but not KORs, whereas dezocine and pentazocine inhibited KOR activities. Subcutaneously injected dezocine-, tapentadol- and pentazocine-induced antinociception dose-dependently, in hot-plate test. Intrathecally injected MOR antagonist CTAP, norepinephrine depletor 6-OHDA and α2-adrenoceptor (α2-AR) antagonist yohimbine partially antagonized dezocine, pentazocine and tapentadol antinociception. Whereas specific KOR antagonist GNTI did not alter their antinociception, the putative inverse KOR agonist nor-BNI reduced dezocine and pentazocine antinociception. Moreover, combined CTAP and 6-OHDA or yohimbine blocked dezocine and tapentadol antinociception but displayed the same partial inhibition on pentazocine antinociception as CTAP alone. Furthermore, compared to morphine and pentazocine, long-term treatment with dezocine and tapentadol produced much less physical dependence-related withdrawal signs, which were restored by spinal 6-OHDA or yohimbine treatment. SIGNIFICANCE: Our findings illustrated that dezocine and tapentadol, but not pentazocine, exert remarkable antinociception in nociceptive pain with less abuse liability via dual mechanisms of MOR activation and NRI.

Novel High Affinity Sigma-1 Receptor Ligands from Minimal Ensemble Docking-Based Virtual Screening.

Sigma-1 receptor (S1R) is an intracellular, multi-functional, ligand operated protein that also acts as a chaperone. It is considered as a pluripotent drug target in several pathologies. The publication of agonist and antagonist bound receptor structures has paved the way for receptor-based in silico drug design. However, recent studies on this subject payed no attention to the structural differences of agonist and antagonist binding. In this work, we have developed a new ensemble docking-based virtual screening protocol utilizing both agonist and antagonist bound S1R structures. This protocol was used to screen our in-house compound library. The S1R binding affinities of the 40 highest ranked compounds were measured in competitive radioligand binding assays and the sigma-2 receptor (S2R) affinities of the best S1R binders were also determined. This way three novel high affinity S1R ligands were identified and one of them exhibited a notable S1R/S2R selectivity.

Sigma 1 Receptor Modulates Optic Nerve Head Astrocyte Reactivity.

Purpose: Stimulation of Sigma 1 Receptor (S1R) is neuroprotective in retina and optic nerve. S1R is expressed in both neurons and glia. The purpose of this work is to evaluate the ability of S1R to modulate reactivity responses of optic nerve head astrocytes (ONHAs) by investigating the extent to which S1R activation alters ONHA reactivity under conditions of ischemic cellular stress. Methods: Wild type (WT) and S1R knockout (KO) ONHAs were derived and treated with vehicle or S1R agonist, (+)-pentazocine ((+)-PTZ). Cells were subjected to six hours of oxygen glucose deprivation (OGD) followed by 18 hours of re-oxygenation (OGD/R). Astrocyte reactivity responses were measured. Molecules that regulate ONHA reactivity, signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-kB), were evaluated. Results: Baseline glial fibrillary acidic protein (GFAP) levels were increased in nonstressed KO ONHAs compared with WT cultures. Baseline cellular migration was also increased in nonstressed KO ONHAs compared with WT. Treatment with (+)-PTZ increased cellular migration in nonstressed WT ONHAs but not in KO ONHAs. Exposure of both WT and KO ONHAs to ischemia (OGD/R), increased GFAP levels and cellular proliferation. However, (+)-PTZ treatment of OGD/R-exposed ONHAs enhanced GFAP levels, cellular proliferation, and cellular migration in WT but not KO cultures. The (+)-PTZ treatment of WT ONHAs also enhanced the OGD/R-induced increase in cellular pSTAT3 levels. However, treatment of WT ONHAs with (+)-PTZ abrogated the OGD/R-induced rise in NF-kB(p65) activation. Conclusions: Under ischemic stress conditions, S1R activation enhanced ONHA reactivity characteristics. Future studies should address effects of these responses on RGC survival.

Boerhaave's syndrome after pentazocine-induced vomiting in a 21-year-old male with asthma: a case report.

Boerhaave's syndrome is an uncommon syndrome characterized by spontaneous rupture of the oesophagus with a high mortality rate. While excessive alcohol intake and binge-eating are the classic precipitants of this syndrome, medication-induced vomiting causing Booerhave's is quite uncommon. Traditionally managed operatively, conservative management is being increasingly reported in selected cases. We report the case of 21-year-old male with who developed sudden onset chest pain and dyspnoea after pentazocine induced vomiting. He was referred after lack of response to initial treatment for acute severe asthma. A chest CT scan showed pneumomediastinum, subcutaneous emphysema and oesophageal tear. He was managed conservatively with oxygen therapy, nil per mouth and antibiotics with improvement of symptoms and discharge after 8 days.

Statistically optimized pentazocine loaded microsphere for the sustained delivery application: Formulation and characterization.

Pentazocine (PTZ) is a narcotic analgesic used to manage moderate to severe, acute and chronic pains. In this study, PTZ loaded Ethyl cellulose microsphere has been formulated for sustained release and improved bioavailability of PTZ. These microspheres were fabricated by oil in water emulsion solvent evaporation technique. A three factorial, three levels Box-Behnken design was applied to investigate the influence of different formulation components and process variables on the formulation response using the numeric approach through the design expert® software. All the formulations were characterized for the morphology, different physicochemical properties and the results were supported with the ANOVA analysis, three dimensional contour graphs and regression equations. The maximum percentage yield was 98.67% with 98% entrapment of PTZ. The mean particle size of the formulations ranges from 50-148µm, which directly relates to the concentration of polymer and inversely proportional to the stirring speed. SEM revealed the spherical shape of PTZ microspheres with porous structures. These are physically, chemically and thermally stable as confirmed through Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD) and thermal gravimetric (TG) analysis respectively. The microspheres provided a sustained release of the PTZ for more than 12 hours, following zero order with fickian and non fickian diffusion. The results indicate that prepared microspheres can be a potential drug delivery system (DDS) for the delivery of PTZ in the management of pains.