Reduction In Pain Responses Research Articles

The Analgesic and Anti-inflammatory Properties of Caffeine Co-administration with Nefopam in Mice

This study aimed to evaluate the analgesic properties of nefopam and the adjuvant effects of caffeine. It also investigated the anti-inflammatory effect of co-administering nefopam and caffeine on Prostaglandin E2 level (PGE2). The study involved 56 female albino mice (Mus musculus), divided into seven groups, eight mice per each group. Group A which served as the control group received distilled water; Group B received 30 mg/kg BW of nefopam orally; Group C received 28.5 mg/BW of nefopam and 5 mg/BW of caffeine orally; Group D received 27 mg/BW of nefopam and 10 mg/BW of caffeine orally; Group E received 25.5 mg/BW of nefopam and 15 mg/BW of caffeine orally; Group F received 24 mg/BW of nefopam and 20 mg/BW of caffeine orally; Group G received 22.5 mg/BW of nefopam and 25 mg/BW of caffeine orally. The nociceptive response was assessed using the formalin test, showing a significant (P<0.05) reduction in pain response (accumulative time of flinching and licking) was the first phase (0-5 minutes) in Group E as well as, a significant (P<0.05) decrease in nociceptive response in flinching and licking in second phase (20-60 minutes) was observed in Group D. However, the Prostaglandin level was significantly (P<0.05) lower in Group C. The study concluded that adding low dosages of caffeine to analgesics can boost pain relief in smaller quantities. Caffeine co-administration with nefopam may exert

Synthesis of Ottonia anisum Extract Mediated ZnO NPs and Their Local Anesthetic, Analgesic and HCl‑induced Acute Lung Injury Activities.

In this study, we outlined the green synthesis of Zinc oxide nanoparticles (ZnO NPs) using the plant-mediated method. Employing the nitrate derivative of Zinc and the extract from the native medicinal plant, Ottonia anisum, the nanoparticles were effectively produced. After obtaining a yellow-colored paste, it was meticulously dried, gathered, and set aside for subsequent examination. The UV-visible spectrometry analysis indicated an absorption peak at 320 nm, which is indicative of ZnO NPs. Characterization techniques, such as XRD and HR-TEM, confirmed the existence of agglomerated ZnO NPs with an average diameter of 40 nm. Through EDS analysis, distinct energy signals for both Zinc and Oxygen were observed, confirming their composition. Furthermore, FT-IR spectroscopy highlighted an absorption peak for Zn-O bonding in the range of 400 to 600 cm -1 . Further, we employed three distinct pain models in mice to evaluate the influence of ZnO NPs on the nociceptive threshold. Our findings revealed that, when orally administered, ZnO NPs at concentrations ranging from 5-20 mg/kg exerted a dose-dependent analgesic effect in both the hot-plate and the acetic acid-induced writhing tests. Moreover, when ZnO NPs were administered at doses between 2.5-10 mg/kg, there was a notable reduction in pain responses during both the initial and subsequent phases of the formalin test, but no change in PGE 2 production within the mice's hind paw was found. On the other hand, acute lung injury studies revealed that the administration of ZnO NPs orally 90 minutes prior to HCl instillation decreased the neutrophil infiltration into the lungs in a doseresponsive manner. This reduction in pulmonary inflammation was paralleled by a significant decrease in lung edema, as evidenced by the reduced total protein content in the BALF. Additionally, the ZnO NPs appeared to recalibrate the lung's redox equilibrium following HCl exposure, which was determined through measurements of ROS, malondialdehyde, glutathione, and catalase activity. All these results further indicated the potential of biofabricated ZnO NPs for future applications in analgesics and acute lung injury treatments.

INVESTIGATING THE ANALGESIC ACTIVITY OF JERUJU LEAF INFUSION (ACANTHUS ILICIFOLIUS L.) ON MALE WHITE MICE (MUS MUSCULUS)

This study investigates the analgesic activity of Jeruju leaf infusion (Acanthus ilicifolius L.) on male white mice (Mus musculus). Acanthus ilicifolius, commonly known as Jeruju, has been traditionally employed for its potential therapeutic properties, including pain relief. The experiment involved administering varying concentrations of Jeruju leaf infusion to the experimental group, while the control group received a placebo. The analgesic effect was assessed using standard pain-inducing stimuli, and the responses were recorded and analyzed. Preliminary findings suggest a dose-dependent response in the experimental group, indicating a potential analgesic effect of Jeruju leaf infusion. The results were statistically significant, demonstrating a reduction in pain responses compared to the control group. Further investigation into the underlying mechanisms and active compounds responsible for the observed analgesic activity is warranted. This study contributes to the growing body of research exploring natural remedies for pain management. The potential analgesic properties of Jeruju leaf infusion highlight its promising role in traditional medicine. Future studies could delve deeper into the pharmacological aspects, dosage optimization, and long-term effects of Acanthus ilicifolius L. in managing pain. The findings may have implications for the development of novel analgesic agents derived from natural sources, offering alternative approaches to pain relief with potential clinical applications.

Evaluation of the analgesic and antipyretic activity of methanol extract of Combretum bauchiense Hutch & Dalziel (Combretaceae) leaves

BackgroundMedicinal plants make up a vital component of therapeutics. The pharmacologic effect of medicinal plants can be said to be related to the nature of their phytochemical constituents or secondary metabolites. Combretum bauchiense is an African folk plant of the family Combretaceae. Over the years Species of the Combretaceae family has been associated with native us as antipyretic and analgesic substances. AimThis study aims to determine the phytochemical composition and evaluate the analgesic and anti-pyretic activity of the methanol extract of Combretum bauchiense (MECB) leaves. Materials and MethodsThe phytochemical analysis and acute toxicity study of MECB was done using standard procedures. The analgesic and antipyretic activity of MECB was investigated using two models each, with Morphine (10 mg/kg) as the standard reference drug for analgesic activity and Paracetamol (150 mg/kg) for antipyretic activity. The analgesic activity of the extract was evaluated using formalin induced pain and tail flick analgesic method and the antipyretic activity was evaluated using baker's yeast and turpentine induced pyrexia. The study was investigated at doses of 100, 200 and 400 mg/kg body weight of the extract. Data was analyzed using One-way Anova followed by Tukey's Post-hoc test and P < 0.05 was considered significant. ResultsThe phytochemical analysis revealed the presence of flavonoids, alkaloids, saponins, tannins, proteins, carbohydrates, glycosides and reducing sugars. No acute toxicity symptoms observed on oral administration of MECB at 5000 mg/kg which indicates the safety of the extract. There was significant (P < 0.05) reduction in pain response of 71.43, 77.92, and 84.41% for 100, 200 and 400 mg/kg respectively for the formalin induced pain. For the tail flick test; 31.0, 56.05 and 48.31% increase in pain response time was observed at the doses of 100, 200 and 400 mg/kg respectively. MECB also showed antipyretic activity of 4.87 and 7.42% in Baker's yeast induced antipyretic model at the doses of 200 and 400 mg/kg respectively. While there was significant (P < 0.05) antipyretic activity; 2.28, 4.29 and 5.13% in the turpentine induced antipyretic model at the doses of 100, 200 and 400 mg/kg of extract respectively. ConclusionThe study shows that the Methanol extract of Combretum bauchiense leaves possesses both analgesic and antipyretic properties and justifies it's use in traditional medicine in the treatment of pain and fever. These results also indicated a possible inhibition of prostaglandin synthesis as the mechanism of antipyretic and analgesic activity of the extract.

Analgesic and Anticancer Activity of Benzoxazole Clubbed 2-Pyrrolidinones as Novel Inhibitors of Monoacylglycerol Lipase.

Ten benzoxazole clubbed 2-pyrrolidinones (11–20) as human monoacylglycerol lipase inhibitors were designed on the criteria fulfilling the structural requirements and on the basis of previously reported inhibitors. The designed, synthesized, and characterized compounds (11–20) were screened against monoacylglycerol lipase (MAGL) in order to find potential inhibitors. Compounds 19 (4-NO2 derivative) and 20 (4-SO2NH2 derivative), with an IC50 value of 8.4 and 7.6 nM, were found most active, respectively. Both of them showed micromolar potency (IC50 value above 50 µM) against a close analogue, fatty acid amide hydrolase (FAAH), therefore considered as selective inhibitors of MAGL. Molecular docking studies of compounds 19 and 20 revealed that carbonyl of 2-pyrrolidinone moiety sited at the oxyanion hole of catalytic site of the enzyme stabilized with three hydrogen bonds (~2 Å) with Ala51, Met123, and Ser122, the amino acid residues responsible for the catalytic function of the enzyme. Remarkably, the physiochemical and pharmacokinetic properties of compounds 19 and 20, computed by QikProp, were found to be in the qualifying range as per the proposed guideline for good orally bioactive CNS drugs. In formalin-induced nociception test, compound 20 reduced the pain response in acute and late stages in a dose-dependent manner. They significantly demonstrated the reduction in pain response, having better potency than the positive control gabapentin (GBP), at 30 mg/kg dose. Compounds 19 and 20 were submitted to NCI, USA, for anticancer activity screening. Compounds 19 (NSC: 778839) and 20 (NSC: 778842) were found to have good anticancer activity on SNB-75 cell line of CNS cancer, exhibiting 35.49 and 31.88% growth inhibition (% GI), respectively.

Fatty acid amide hydrolase inhibition normalises bladder function and reduces pain through normalising the anandamide/palmitoylethanolamine ratio in the inflamed bladder of rats.

Fatty acid amide hydrolase inhibition may be used to control bladder function and pain by modulating endocannabinoid levels in cystitis. We studied the effect of the peripherally restricted fatty acid amide hydrolase inhibitor URB937 in bladder reflex activity and bladder pain using the lipopolysaccharide model of cystitis. We also correlated the URB937's effects with tissue levels of the endocannabinoids anandamide and palmitoylethanolamine. URB937 did not change the reflex activity of normal bladders. In inflamed bladders, URB937 had a U-shaped dose-response curve; following an initial cannabinoid receptor type 1-mediated reduction in pain responses and normalisation of bladder reflex activity, URB937 gradually increased both pain responses and bladder reflex activity through the transient receptor potential ion channel subfamily V member 1. Chronic cystitis increased the tissue levels of anandamide and decreased those of palmitoylethanolamine. At the dose that normalised bladder reflex activity and decreased pain responses, URB937 normalised the levels of anandamide and palmitoylethanolamine in the bladder. At high doses that induced excitatory effects, URB937 apparently did not change anandamide and palmitoylethanolamine levels, which therefore were in the range of the inflamed bladder. Fatty acid amide hydrolase inhibition results in complex changes in bladder endocannabinoid levels. The therapeutic effect of fatty acid amide hydrolase inhibitors is not related to increase in anandamide levels but rather a normalisation of the anandamide and palmitoylethanolamine level ratio.

EFFECTS OF CINNAMOMUM ZEYLANICUM BARK EXTRACT ON NOCICEPTION AND ANXIETY LIKE BEHAVIOR IN MICE

Objectives: The aim of the study was to assess the effect of the extract of Cinnamomum zeylanicum (CZ) bark in the experimental models of pain and anxiety-like behavior in mice.&#x0D; Methods: The extract of CZ bark was administered at the doses of 100, 200, and 400 mg/kg, per orally (p.o) and morphine used as a positive control for pain models, was administered at the dose of 5 mg/kg, intraperitoneally (i.p.). Antinociceptive activity was evaluated using three experimental animal models of pain, namely, tail flick, hot plate, and formalin test. Elevated plus maze test was used to assess the effect on anxiety-like behavior. Rotarod apparatus and actophotometer were used to test muscle coordination and locomotor activity, respectively.&#x0D; Results: Administration of CZ bark extract in the dose of 200 and 400 mg/kg showed significantly increased in the tail-flick latency and latency to reaction time in hot plate test as compared to the control group. In the first phase (0–5 min) of the formalin test, a significant reduction in the pain response was found in CZ (200 and 400 mg/kg) and morphine-treated groups, however during the second phase (30–35 min) significant reduction in formalin-induced pain response was observed in 100, 200, and 400 mg/kg CZ extract-treated group when compared to control group. CZ extract administration at 200 and 400 mg/kg dose caused a significant increase in the percentage of time spent in open arms in the elevated plus maze as compared to the control group.&#x0D; Conclusion: Results suggest that CZ bark extract possesses the antinociceptive activity and modulates anxiety-like behavior.

Brain functional properties predict placebo analgesia in knee osteoarthritis

Purpose: Chronic pain is the primary complaint associated with OA, serving as a predictor of physical dysfunction and muscular weakness. As blinded, randomized placebo-controlled trials of therapeutic agents in OA have repeatedly demonstrated a marked reduction in pain response to placebo, studies of the brain response to placebo may inform on brain properites of OA itself. Although mechanisms of placebo response have been repeatedly studied in humans, we are the first to investigate its underlying brain properties in a clinical drug study design. Here we investigate the possibility of identifying brain properties that predispose different OA patients to placebo analgesia. Methods: 20 patients meeting ACR criteria for knee OA were enrolled into this single-blinded 4 week study. At baseline, patients were instructed that they might be receiving either active drug or placebo; however they all were given placebo for 2 weeks after which the treatment was stopped. At baseline and at the end of the 2 weeks the patients underwent an fMRI brain scan as well as a structural high resolution T1 brain scan; efficacy reports were collected on both occasions. Two weeks post cessation of medication patients were contacted again and same efficacy reports were recollected. The primary efficacy measure was Visual Analogue Scale 24 hour average pain rating. Secondary efficacy measures included WOMAC Index; Pain detect, Beck depression Index (BDI), and Pain catastrophizing scale (PCS). In addition, 17 healthy age- and gender-matched participants without knee pain were scanned at baseline to serve as controls. For the analysis, the patient groups were stratified as responders vs. non-responders to the placebo treatment based on a decrease in visual analogue scale (VAS) pain rating equal to or greater than 20% from baseline. Analysis was then conducted to determine differences in brain fMRI data between OA patients and controls as well as between OA placebo-responders vs. OA placebo-non-responders. Results: Of the 20 patients enrolled, 9 were male and 11 female; mean age was 57.8±6.6 years; mean duration of OA was 12.1±10.0 years. 3 patients discontinued prior to their week 2 visit; of the remainder, 8 responded to placebo (mean VAS dropped from 72.5±14.1 to 32.5±20.5, i.e., 56% decrease in VAS) whilst 9 did not show any significant change in reported pain (VAS changed from 66.7±8.2 to 70±4.7, i.e., a mean increase of 7%). OA vs controls: By comparing the general number of connections across all brain regions between OA patients and controls we conclude that the region constituted by the medial prefrontal cortex (mpfc) and nucleus accumbans as well as the caudate is more connected (p <0.05, corrected for multiplicity) in patients with OA than in controls. OA-responders vs. OA-non responders: The secondary somatosensory cortex (S2) was generally more linked in the OA non-responders (p-corrected < 0.05). In this group, the S2 region displayed significantly more connectivity with the ventro-lateral prefrontal cortex (vlpfc). Moreover, the vlpfc showed more connectivity (p-corrected < 0.05) with the part of the brain network identified for OA, namely mpfc. Both S2 counts and vlpfc-mpfc connectivity predicted with very high accuracy (AUC=. 97 and .96, respectively) responders to placebo. Conclusions: In this study, we have shown that brain information sharing (functional connectivity) is different in OA in contrast to healthy control subjects. Furthermore, analysis of activity of components of this network predicts the response to placebo. Thus, placebo analgesia is predictable from brain connectivity (information shared between brain regions), prior to start of the placebo treatment trial. These results suggest that distinct sub-groups of OA have distinct propensities for placebo based on their brain states. The specific characteristics that distinguish between these groups remains to be identified. The results of the present study have important implications regarding OA, clinical trials in OA, and for future designs of treatments for OA.

Effects of a local anaesthetic and NSAID in castration of piglets, on the acute pain responses, growth and mortality

The present study addresses the questions whether on-farm use of local anaesthesia with lidocaine leads to a reduction in pain responses during castration, and whether the non-steroidal anti-inflammatory drug meloxicam improves technical performance after castration of piglets. Five treatments were included in the study: (1) castration without anaesthesia or analgesia (CAST), (2) castration after local anaesthesia with lidocaine (LIDO), (3) castration after administration of meloxicam (MELO), (4) castration after lidocaine and meloxicam (L + M) and (5) sham castration (SHAM). To reduce litter influences, each treatment was present in each of the 32 litters (n = 32 per treatment). During castration, vocalizations were recorded continuously. Blood samples were collected 15 min before and 20 min after castration for determination of plasma levels of total cortisol, glucose, lactate and creatine kinase (CK). Mortality was registered and piglets were weighed several times to calculate growth. Several aspects of vocalizations during castration showed consistent and significantly different levels in CAST compared with LIDO, L + M and SHAM. CAST piglets squealed longer, louder and higher. Vocalizations of MELO piglets most resembled those of CAST. An increase in cortisol was seen in all treatments. However, in SHAM piglets this increase was significantly lower than in the other treatments. LIDO piglets showed a significantly smaller increase in plasma cortisol levels compared with CAST and MELO. L + M piglets differed significantly only from the SHAM group. Lactate levels differed significantly between LIDO and MELO, the level in LIDO being decreased after castration. In the other treatments an increase was measured. No treatment effects were found in plasma glucose and CK levels, nor in growth and mortality of the piglets. In conclusion, on the basis of vocalizations and plasma cortisol, local anaesthesia with lidocaine reduces pain responses in piglets during castration. A positive effect of meloxicam on technical performance was not found.

1368 SURFACTANT PROTEINS A AND D INHIBIT UROPATHOGENIC ESCHERICHIA COLI BINDING TO UROTHELIAL CELLS

pain. Here we examine whether an ASB strain can reduce NU14induced acute pelvic pain and colonization compared with ciprofloxacin and lidocaine. METHODS: Acute UTI pain was induced by bladder instillation of clinical isolate NU14. After establishment of NU14-induced acute pain, mice were treated with saline intraperitoneally (IP or bladder), ciprofloxacin IP, lidocaine, or an ASB strain instilled into the bladder, vaginal introitus or colon. Pelvic pain was assessed using von Frey filament stimulation to the pelvic region of female B6 mice at baseline, 1 day after NU14 infection and 1, 4 and 24 hours after treatment. NU14 bladder colonization was examined 24 hours after treatment. RESULTS: NU14-infected mice instilled with 2% lidocaine into the bladder, vaginal introitus or colon exhibited a 70%, 72% and 54% reduction in pelvic pain at 1 hour after treatment respectively. NU14infected mice instilled with an ASB strain into the bladder, vaginal introitus, or colon exhibited a 74%, 73%, and 25% reduction in pain responses respectively 24 hours after treatment. In contrast, ciprofloxacin treated mice exhibited no reduction in pain responses 1, 4 and 24 hours after treatment having similar levels of pain to saline mice. NU14-infected mice instilled with an ASB strain into the bladder, vaginal introitus or colon exhibited a 95%, 84% and 42% reduction in bladder colonization of NU14 respectively compared to bladder instilled saline mice. CONCLUSIONS: These data demonstrate that an ASB strain can rapidly attenuate pelvic pain and colonization in an acute UTI pelvic pain model. These ASB-induced reductions occurred when administered either in bladder or the vaginal introitus, suggesting that a vaginal suppository may be considered as a future novel therapeutic route to attenuate pelvic pain and colonization while reducing the emergence of antimicrobial resistance.

Intrathecal ketorolac tromethamine produces analgesia after chronic constriction injury of sciatic nerve in rat.

The study compared analgesic efficacy of intrathecally administered ketorolac tromethamine (K) and morphine hydrochloride (M) (in equimolar doses) in the chronic neuropathic pain model, induced by chronic constriction injury (CCI) of the sciatic nerve in rat. Male Sprague-Dawley rats (n = 30) were anaesthetized with halothane and an intrathecal catheter was inserted to the mid-lumbar level of the spinal cord. On the 5th post-operative day, rats were anaesthetized with halothane and four ligatures were loosely applied around the right sciatic nerve. Seven days later, those animals were randomly divided into three groups and were injected with either saline, M (20 nmoles) or K (20 nmoles). Two pain responses (foot-withdrawal delay and hind paw elevation time) were measured on both sides using the radiant heat method. Further, thermal ("cold") allodynia was assessed by measuring of the total time of hind paw elevation in animals placed on the cold metal plate. Twenty nmoles of M and K injected intrathecally produced decrease of differential pain score calculated for both measured responses (hind paw withdrawal and hind paw elevation), compared with saline injected animals (P < 0.05). The reduction in pain response produced by K was less (P < 0.05). than the reduction in pain response observed in the animals receiving intrathecal M. Measurement of cold allodynia revealed that the animals in M and K injected groups demonstrated decreases in the total hind paw elevation time, when compared with saline-injected animals (P < 0.05). M and K produced hypoalgesia after intrathecal administration in rats with CCI, with M being more potent than K at an equimolar dose range. The analgesic effect of K was equal to equimolar doses of M for alleviation of cold allodynia.

Long‐Term Reduction in the Number of C‐Fibre Nociceptors Following Capsaicin Treatment of a Cutaneous Nerve in Adult Rats

The structure and function of C- and A-fibres have been studied 3 - 12 months following a single 30 min exposure of the saphenous nerve of adult rats to 1% capsaicin. Examination of nerve cross-sections showed that the number of C-fibres was reduced by 36%, but A-fibres were unaffected. The remaining C-fibres included many that were unusually small in size. The changes were not restricted to the treatment site but were found over at least a further 10 mm proximal and distal to it. In treated nerves, the C-fibre component of the compound action potential was reduced in size relative to the Aalphabeta component. Single unit studies revealed that an unusually high proportion of C-fibres had no cutaneous receptive field (54%, compared with 28% in controls). There was no such change for A-fibres. The conduction velocity range for C-fibre units in treated nerves was almost normal, but this sample contained an unusually low proportion of polymodal nociceptors. Allowing for the fall in total numbers and the reduction in units with cutaneous receptive fields, it was calculated that overall the numbers of C-polymodal nociceptor units had fallen by 74%. No significant changes in number had occurred in the other classes of C-afferents. The reduction in the numbers of nociceptive C-fibres is likely to be the direct cause of the reduction in pain responses and in neurogenic inflammation that several groups have reported following treatment of adult rats with capsaicin. Reduction in the numbers of C-fibre is also likely to be the reason for reduced neuropeptide levels seen in tissues innervated by treated nerves.