Intraperitoneal Injection Of Acetic Acid Research Articles

The Trial on the Effectiveness of Honey on White Rats Using Geliate Acetate Method An Experimental Study in Male Wistar Rat

Background: Pain is the most common complaint of a disease that can be reduced using the analgesic drugs. Besides the pharmacological medication, the traditional medications are available including honey containing flavanoid. The compound can protect the lipid membrane from the damage and inhibit cyclooxygenase, the main path of the synthesis mediator for pain like prostaglandin. This study aims at finding out the efficacy of analgesic of honey using geliate asetate method.Design and methods: In an experimental study using post test only control group design, 25 Wistar rat (80-90 days, BW 180-220 gr) were randomly divided into 3 groups of 5 mice each. Gp1: =aquadest (negative control), Gp2: 0.675 g/BW honey, Gp3: 1.35g honey Gr 4: 2.7 g/kgBW honey and Gr 5 (possitive control): 4.5 mg/ BW of paracetamol. 5 minutes after the treatment, an intraperitoneal injection of acetic acid was given for all groups. Anova followed by post Hoc test was used for data analysis.Result: The honey concentration of 50% (1.35) g was found to have increasing effect of analgesic while the concentration of 25% and 100 % showed a reducing analgesic effect.Conclusion: Honey has been shown to have an analgesic effect in mice with the effective concentration of 50% (1.35 g/kgBW) (Sains Medika, 3(1):48-53).

Anti-hyperalgesic effect of an ethanolic extract of propolis in mice and rats.

Propolis, or bee glue, which contains a complex mixture of secondary metabolites, has long been used in many countries for the management of several diseases. The purpose of this study was to evaluate, by means of several pharmacological models, the anti-hyperalgesic effect of propolis collected in the south of Brazil. The abdominal constrictions induced in mice by intraperitoneal injection of acetic acid (0.6%), kaolin (50 mg kg-1) or zymosan (40 mg kg-1) were inhibited to different extents by an extract of propolis (1-60 mg kg-1) administered intraperitoneally 30 min earlier; mean ID50 (concentrations resulting in 50% inhibition) values were 2.7, 10.8 and 10.7 mg kg-1, respectively, and maximum inhibition was 58 +/- 5, 57 +/- 10 and 51 +/- 5%, respectively. Given orally (25-200 mg kg-1, 1h previously) propolis also inhibited the abdominal constrictions induced by acetic acid (maximum inhibition 43 +/- 5%). When injected intraperitoneally (3-60 mg kg-1, 30 min previously), propolis attenuated both the neurogenic (first phase) and inflammatory (second phase) pain responses and paw oedema caused by intraplantar injection of formalin (2.5%); maximum inhibition was 32 +/- 5, 43 +/- 6 and 19 +/- 2%, respectively. Oral administration of propolis (25-200 mg kg-1, 1 h previously) inhibited both phases and reduced the oedema formation associated with the second phase of the formalin test (maximum inhibition 22 +/- 5, 33 +/- 6 and 26 +/- 3%) and extract of propolis (3-30 mg kg-1 i.p. or 25-100 mg kg-1 p.o., respectively 30 min and 1 h previously) significantly inhibited capsaicin-induced pain with maximum inhibition of 39 +/- 8 and 41 +/- 8%, respectively. When assessed in the Randall-Sellito test of pain, the extract of propolis (3-30 mg kg-1, i.p., 30 min previously) significantly reversed the hyperalgesia induced by intraplantar injection of bradykinin (3 nmol per paw) in rats (P < 0.01). In contrast with morphine the extract of propolis (< or = 100 mg kg-1, 30 min previously) was ineffective when assessed in the tail-flick and hot-plate thermal assays. Naloxone (5 mg kg-1 i.p.) reversed (P < 0.01) the effect of morphine (5 mg kg-1 s.c.) by 70 and 94% respectively in the first and second phases of the formalin test, but did not interfere with the analgesic effect of propolis (10 mg kg-1 i.p., 30 min previously). These results show that ethanolic extract of propolis, given systemically, has significant anti-hyperalgesic action when assessed in chemical, but not thermal, models of nociception in mice and rats. Its analgesic action seems to be unrelated to release or activation of the opioid system.

Anti-inflammatory and Analgesic Effect of Plumbagin through Inhibition of Nuclear Factor-κB Activation

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) (PL) is a naturally occurring yellow pigment found in the plants of the Plumbaginaceae, Droseraceae, Ancistrocladaceae, and Dioncophyllaceae families. It has been reported that PL exhibits anticarcinogenic, anti-inflammatory, and analgesic activities. However, the mechanism underlying its anti-inflammatory action remains unknown. In the current study, we investigated and characterized the anti-inflammatory and analgesic effects of PL orally administrated in a range of dosages from 5 to 20 mg/kg. We also examined the role of nuclear factor κB (NF-κB) and proinflammatory cytokines and mediators in this effect. The results showed that PL significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan and various proinflammatory mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2). PL reduced the number of writhing episodes of mice induced by the intraperitoneal injection of acetic acid, but it did not reduce the writhing episode numbers induced by MgSO(4) in mice or prolong the tail-flick reaction time of rats to noxious thermal pain. Mechanistic studies showed that PL effectively decreased the production of the proinflammatory cytokines interleukin 1β, interleukin 6, and tumor necrosis factor α. It also inhibited the expression of the proinflammatory mediators inducible nitric-oxide synthase and cyclooxygenase 2, whereas it did not inhibit the expression of cyclooxygenase 1. Further studies demonstrated that PL suppressed inhibitor of κBα phosphorylation and degradation, thus inhibiting the phosphorylation of the p65 subunit of NF-κB. This study suggests that PL has a potential to be developed into an anti-inflammatory agent for treating inflammatory diseases.

Effects of anesthetic propofol on release of amino acids from the spinal cord during visceral pain

As one of general anesthetics, propofol, has been used for surgical procedures of visceral organs. However, the mechanisms underlying the action of propofol on visceral nociception remain controversial. The aim of this study is to test whether the antinociception of systemic administration of propofol against visceral stimuli is related to the changes in release of excitatory and inhibitory amino acids in the spinal cord. The spinal microdialysis catheters were implanted subarachnoidally via the atlanto-occipital membrane in healthy SD rats. The rats received an intraperitoneal injection of acetic acid for visceral pain induction 10 min after intraperitoneal pretreatment with vehicle or propofol (100 mg/kg). The acetic acid-induced writhing assay was used to determine the degree of antinociception. Cerebrospinal fluid dialysate was collected by microdialysis from the spinal subarachnoid space before pretreatment and after visceral pain induction. Visceral pain-induced release of amino acids into the dialysate, including glutamate, aspartate, and γ-amino butyric acid was evaluated by measuring the changes in the concentrations of these amino acids. Acetic acid increased release of aspartate and glutamate, and decreased release of γ-amino butyric acid in the cerebrospinal fluid as measured by microdialysis. Pretreatment with propofol significantly decreased writhing responses induced by visceral pain, suppressed the visceral pain-induced aspartate and glutamate release, and reversed the decreased release of γ-amino butyric acid in the cerebrospinal fluid. These data provide evidence for a potential mechanism for the antinociceptive effects of propofol on visceral nociception.

Retracted: Comparison of the therapeutic effects of different compositions of muskone in the treatment of experimental myocardial infarct in rats and analgesia in mice

The aim of this study was to compare the therapeutic effects of muskone, a traditional preparation containing slender Dutchmanspipe root (MCS) used to treat angina pectoris and related conditions, muskone containing inula root (MCI) in place of MCS, and muskone (M) without either slender Dutchmanspipe root (S) or inula root (I) on acute myocardial infarct (AMI) in rats and the pain response in mice. The AMI model was established by ligating the left anterior descending coronary artery (LAD). The AMI rats were treated with MCS, MCI, M, S and I, respectively, before the surgical operation. Plasma endothelin (ET), 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), thromboxane (TXB(2)) and myocardial apoptosis were detected, the ratio of 6-keto-PGF(1alpha) level to TXB(2) level (6-keto-PGF(2alpha)/TXB(2)) was calculated, and the infarct size was determined. In the pain relieving study, the prophylactic treatments with MCS, MCI, M, S, I and aspirin were administered to the mice once a day for 5 days, the response latency and the number of abdominal contractions after the stimulus of intraperitoneal injection of acetic acid were recorded. The results show that MCS, MCI and M significantly ameliorated plasma ET, TXB(2), 6-keto-PGF(1alpha) and 6-keto-PGF(2alpha)/TXB(2) levels, reduced infarct size and opposed myocardial apoptosis. Simultaneously, they also significantly reduced the abdominal contractions and also prolonged the response latency induced by acetic acid in the mice. S and I only showed a degree of relieving pain, but their efficacy was weaker than that of MCS, MCI and M, and they had little cardioprotective effect. In conclusion, MCS, MCI and M had a significant cardioprotective and analgesic effect, and they had similar efficacy. S and I only had a secondary analgesic effect. Removing S from the MCS or replacing S with I did not influence the cardioprotective effect and analgesic effect.

Antinociceptive activity of steroid alkaloids isolated from Solanum trilobatum Linn.

Solasodine (1) was isolated for the first time from the roots of Solanum trilobatum Linn., a member of the Solanaceae, and assessed for its presumed antinociceptive activity using several experimental murine models, viz. the writhing, formalin, and hot plate tests. When used at doses of 2, 4, and 8 mg/kg, this steroidal alkaloid caused a significant and dose-dependent decrease in the nociception induced by an intraperitoneal injection of acetic acid (p < 0.001). It also led to a significant reduction of the painful sensation caused by formalin in both phases of the formalin test (p < 0.001). Furthermore, the alkaloid produced a significant increase in the reaction time in the hot plate test (p < 0.001). These results suggest that solasodine elicited antinociceptive activity through both central and peripheral mechanisms.

Central effect of histamine on acetic acid-induced visceral nociception in rats

In the present study, the effects of intracerebroventricular (ICV) injections of histamine, chlorpheniramine (H1-receptor antagonist) and ranitidine (H2-receptor antagonist) were investigated on visceral nociception induced by an intraperitoneal (IP) injection of acetic acid in rats. The latency time to the beginning of the first abdominal wall contraction (the first writhe) was recorded and the number of writhes was counted for 1 h after the IP injection of acetic acid (1 ml, 1%). All treatments (histamine: 2.5–80 µg, chlorpheniramine and ranitidine: 5–80 µg) did not influence the latency time to the beginning of the first writhe significantly except for the 40 ?g dose of histamine, which significantly increased the latency time (p

Effect of spironolactone on pain responses in mice.

The effects of spironolactone, a non-selective aldosterone antagonist, were examined on thermally-induced pain using the hot-plate and tail-flick tests, on chemogenic pain induced by intraplantar capsaicin, on electrically-induced pain, on visceral nociception induced by intraperitoneal acetic acid injection and on haloperidol-induced catalepsy in mice. Spironolactone significantly shortened response latency in the mouse tail-flick test but produced modest decreases in response latencies in the mouse hot plate test. The drug reduced the antinociceptive effect of tramadol in the hot plate test. Spironolactone in addition decreased nociceptive thresholds of electrically-induced pain in mice. In contrast, spironolactone elicited significant antinociceptive actions in the mouse acetic-acid-induced writhing assay and at doses of 20-160 mg/kg decreased capsaicin-induced chemogenic pain. Spironolactone at doses of 40 or 80 mg/kg reduced spontaneous activity and produced a significant impairment on the rotarod test in mice. The drug (10-80 mg/kg) increased the duration of catalepsy induced by haloperidol by 56.3-188.5 %. In conclusion, spironolactone increased pain behavior in a dose-dependent manner in models of thermal and electrical pain, but decreased inflammatory visceral pain due to intraperitoneal acetic acid and chemogenic pain due to intraplantar capsaicin. The effect of spironolactone on various types of pain needs further evaluation.

Antinociceptive effect of proanthocyanidins from Croton celtidifolius bark

The chemical composition of the chromatography 63 subfraction (63SF) from the ethyl acetate soluble fraction of the crude extract of Croton celtidifolius bark presented a high content of total proanthocyanidins (75.0+/-2.3%). HPLC analysis of 63SF revealed a dimeric profile (e.g.catechin-(4alpha-->8)-catechin and gallocatechin-(4alpha-->8)-catechin) and polymeric proanthocyanidins. In pharmacological investigations, 63SF administered intraperitoneally exhibited dose-dependent antinociceptive activity against several chemical stimuli, including the intraperitoneal injection of acetic acid (ID50 (the dose of 63SF which was able to reduce the nociceptive response by 50% relative to the control value)=0.9 (0.5-1.6)) and the intraplantar injection of capsaicin (ID50=13.0 (10.0-17.0)), glutamate (ID50=4.0 (2.0-7.0)) and formalin (ID50 first phase=36.0 (24.0-53.0) and late phase=11.0 (8.0-14.0)). 63SF administered orally exhibited an antinociceptive effect in the formalin test (ID50 first phase=125.0 (89.0-177.0) and late phase=65.0 (33.0-95.0)). In the same test, 63SF was effective when given soon after the first phase, as well as exhibiting therapeutic activity. Furthermore, 63SF was effective in models of thermal nociception including tail-flick and hot-plate tests. When the mice were treated in the neonatal period with capsaicin, the antinociceptive effect of 63SF in the first phase of the formalin test was abolished, but pretreatment with naltrexone did not change the antinociceptive effect of 63SF. Together, these results provide evidence that 63SF exerted a pronounced systemic antinociception against chemical (acetic acid, formalin, glutamate and capsaicin tests) and thermal (hot-plate and tail-flick tests) nociceptive models of pain in mice at a dose that did not interfere with the locomotor activity. The mechanism by which this sub-fraction produced antinociception remains unclear, but it is unlikely to involve the activation of the opioid system. However, unmyelinated C-fibres sensitive to treatment with capsaicin are likely to participate in antinociception caused by 63SF.

Analgesic and Anti-inflammatory Effects of Rosa damascena Hydroalcoholic Extract and its Essential Oil in Animal Models.

Extracts obtained from the petals of Rosa damascena (Rosaceae) are used in Iranian folk medicine as remedies for the treatment of some inflammatory diseases. In this study the hydroalcoholic extract and essential oil of the plant were investigated for its possible anti-inflammatory and analgesic activities. The extract was administered at the doses (p.o.) of 250, 500 and 1000 mg/kg and the doses of essential oil were 100, 200 and 400 μL/kg. The acetic acid-induced writhing response, formalin-induced paw licking time in the early and late phases and light tail flick test were used in mice to assess analgesic activity. For evaluation of anti-inflammatory effect carrageenan-induced paw edema served as a valid animal model in rats. The extract significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and also showed potent analgesic effect in both phases of formalin test but not in light tail flick test. In addition, the higher dose of the extract significantly (P < 0.05) reduced carrageenan-induced paw edema. Essential oil of the plant at all administered doses failed to show any analgesic or anti-inflammatory effect in above mentioned tests. These results provide support for the use of hydroalcoholic extract of Rosa damascena in relieving inflammatory pain, and insight into the development of new agents for treating inflammatory diseases.

Anti-inflammatory effects and quantitative study of the combinations of active ingredients of Painong powder in mice

To study the anti-inflammatory effects of the combinations of active components of Painong powder, a compound traditional Chinese herbal medicine, and the quantitative analysis of their interactions. The mouse model of acute inflammation with increase of capillary permeability was induced by intraperitoneal injection of acetic acid. An orthogonal design with 2 levels (used and unused) was applied to assign the combinations groups of active ingredients including naringin and neohesperidin, peoniflorin, and platycodin. Aspirin and normal saline were administered as control. The pharmacodynamic interactions were analyzed by the optical density (OD) of infiltrated Evans blue. The different combinations of active ingredients showed anti-inflammatory effect with different degree, and the predicted values of OD varied from 0.115 to 0.170. The maximum anti-inflammatory effect was from the combination of naringin, neohesperidin, paeoniflorin and platycodin, better than that of the saline group (P < 0.01). However, there was no significant difference as compared with the aspirin group (P > 0.05). Paeoniflorin showed a dominant contribution to the formula, and platycodin the least. The combination of all active components exhibited synergism. The results suggest that all the ingredients are efficacious constituents of the formula, and paeoniflorin shows a dominant contribution to the formula. More information about prescription compatibility can be obtained by the orthogonal simulation method.

Antinociceptive properties of Trigonella foenumgreacum seeds extracts.

Trigonella foenum-graecum L. (Leguminosae), known in Morocco as “Helba”, is used in folk medicine for its anti-ulcer, anti-inflammatory, cicatrizing activities and to treat various pain-related physiological conditions. In the present study, we attempted to verify the possible antinociceptive action of different extracts obtained from the seeds of this plant. Three experimental models were used (acetic acid, formalin, and hot-plate tests) in order to characterize the analgesic effect. The extracts significantly, and in a dose-dependent manner, reduced the pain induced by intraperitoneal injection of acetic acid. In the formalin test, the extracts, except ethyl acetate extract (Tfge), significantly reduced the painful stimulus but only in the early phase of the test. On the contrary, these extracts, except Tfge, were ineffective to increase the latency of licking or jumping in the hot plate test. These results suggest that the compounds present in the extracts activated both central and peripheral mechanisms to elicit the analgesic effect. Key words: Trigonella foenum-graecum seeds, writhing test, formalin test, hot-plate test, nociception, mice, rats.

Effects of Chlorpheniramine and Ranitidine on the Visceral Nociception Induced by Acetic Acid in Rats: Role of Opioid System

In this study, effects of chlorpheniramine (H1-receptor blocker), ranitidine (H2-receptor blocker), morphine (an opioid agonist) and naloxone (an opioid antagonist) in separate and combined treatments were investigated on the visceral nociception in rats. Visceral nociception was induced by intraperitoneal injection of acetic acid (1 mL, 1%). The latency time to the beginning of the first abdominal wall contraction (first writhe) was measured and the numbers of writhes were counted for 1 h after acetic acid injection. Intraperitoneal injections of chlorpheniramine and ranitidine significantly (p < 0.05) increased the latency time to the beginning of the first writhe and also significantly (p < 0.05) decreased the numbers of writhes. The same results were obtained after subcutaneous injection of morphine. Subcutaneous injection of naloxone did not change the intensity of visceral nociception, but significantly (p < 0.05) prevented the morphine-induced antinociception. Intraperitoneal injection of chlorpheniramine significantly (p < 0.05) enhanced the morphine-induced analgesia, but did not reverse the effect of naloxone on nociceptive responses. Intraperitoneal injection of ranitidine, with no effect on the morphine-induced antinociception, significantly (p < 0.05) reversed the effect of naloxone on pain responses. These results suggest that both chlorpheniramine and ranitidine exert antinociceptive effect in the visceral nociception. In addition, morphine through a naloxone-dependent mechanism produces visceral antinociception. Moreover, the endogenous opioid system may participate in the chlorpheniramine- but not in the ranitidine-induced antinociception.

Role of enhanced noradrenergic transmission within the ventral bed nucleus of the stria terminalis in visceral pain-induced aversion in rats

Pain is an unpleasant sensory and emotional experience. We demonstrated the crucial role of the bed nucleus of the stria terminalis (BNST) in the negative affective component of somatic and visceral pain induced by intraplantar formalin and intraperitoneal acetic acid injections, respectively, in rats. Recently, we reported the involvement of enhanced noradrenergic transmission via β-adrenoceptors within the ventral BNST (vBNST) in formalin-induced aversion. Here, we examined the role of intra-vBNST noradrenergic transmission in the negative affective component of visceral pain induced by intraperitoneal acetic acid injection. In vivo microdialysis showed that extracellular noradrenaline levels within the vBNST significantly increased after intraperitoneal acetic acid injection. Using a conditioned place aversion (CPA) test, we found that intra-vBNST injection of timolol, a β-adrenoceptor antagonist, dose-dependently attenuated the acetic acid-induced CPA without reducing nociceptive behaviors. These results suggest that enhanced noradrenergic transmission via β-adrenoceptors within the vBNST plays a pivotal role in the negative affective, but not sensory, component of visceral pain.

The Effect of Curcumin (Active Substance of Turmeric)on the Acetic Acid-Induced Visceral Nociception in Rats

In the present study, the effect of chronic oral administration of curcumin in the presence or absence of morphine and noloxone was investigated on the visceral nociception induced by acetic acid in rats. Intraperitoneal injection of acetic acid (1 mL, 2%) produced contractions in the abdominal musculature (writhes). The latency time to the beginning of the first writhe was measured and the total number of writhes in the 1 h after acetic acid injection was counted. The latency time to the beginning of the first writhe was significantly (p < 0.05) increased and the number of writhes was significantly (p < 0.05) decreased by curcumin (20 and 40 mg kg(-1) body weight). The same results were obtained after subcutaneous injection of morphine (1 mg kg(-1) b.wt.). Naloxone at the dose of 1 mg kg(-1) body weight had no effect on pain intensity. Curcumin significantly (p < 0.05) enhanced the effect of morphine on the visceral pain responses, however did not reverse the effect of naloxone. Present data suggest that in the acetic acid-induced visceral nociception of rats, curcumin may produce an antinociceptive effect and the endogenous analgesic opioid system is involved in the curcumin-induced antinociception.

Does the medial thalamus play a role in the negative affective component of visceral pain in rats?

Pain consists of sensory and negative affective components. Using a conditioned place aversion (CPA) paradigm, we investigated whether the medial thalamus (MT) played a role in the affective component of visceral pain induced by intraperitoneal injection of acetic acid into male Long-Evan rats. Acetic acid produced writhing response as well as CPA. The bilateral MT-lesions resulted in slight reduction of writhing response, but CPA was not affected. The results suggest that while MT may play a role in visceral nociception, it does not participate in the negative affective component of visceral pain.

The Involvement of the Nociceptin Receptor in the Antinociceptive Action of Nitrous Oxide

Nociceptin and its receptor are widely expressed in the central nervous system and are involved in the modulation of nociception. We have previously reported that the minimum anesthetic alveolar concentrations for volatile anesthetics do not differ between nociceptin receptor knockout (NOP-/-) mice and wild-type (NOP+/+) mice. In the present study, we investigated whether the nociceptin system is involved in the antinociceptive action of nitrous oxide. Using the acetic acid-induced writhing test, we showed that nitrous oxide had significantly less analgesic action in NOP-/- mice than in NOP+/+ mice. Furthermore, when anesthetized with a mixture of halothane and nitrous oxide (70%), intraperitoneal injection of acetic acid resulted in an increase of plasma adrenocorticotropic hormone concentrations in NOP-/- mice but not in NOP+/+ mice. An immunohistochemical study showed that nitrous oxide exposure induced c-Fos expression in the spinal cords of NOP+/+ mice but not in those of NOP-/- mice. These results together suggest that the antinociceptive action of nitrous oxide is, at least partly, mediated by the nociceptin system.

Antinociceptive and anti-inflammatory effects of Thespesia populnea bark extract

The ethanolic extract of Thespesia populnea bark (TPE) was investigated for anti-inflammatory and analgesic activity at the doses (p.o.) of 100, 200 and 400 mg/kg body weight. For evaluation of inflammation carrageenan-, histamine- and serotonin-induced paw edema served as acute models and formaldehyde-induced arthritis served as a chronic model in rats. The acetic acid-induced writhing response and formalin-induced paw licking time in the early and late phases of mice were used to assess analgesic activity. The higher doses of TPE (200 and 400 mg/kg, p.o.) were inhibiting carrageenan, histamine and serotonin-induced paw edema as well as formaldehyde-induced arthritis successfully. In addition, TPE (200 and 400 mg/kg, p.o.) significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and late phase of pain response induced by an subplantar injection of formalin in mice. Furthermore, our phytochemical studies indicated that the ethanolic extract of bark contains alkaloids, carbohydrates, protein, tannins, phenols, flavonoids, gums and mucilage, saponins and terpenes. From acute oral toxicity studies (OECD-423 guidelines), no mortality was observed even at highest dose of TPE (2000 mg/kg, p.o.).

Targeting Pain-Suppressed Behaviors in Preclinical Assays of Pain and Analgesia: Effects of Morphine on Acetic Acid-Suppressed Feeding in C57BL/6J Mice

Pain increases the rate, frequency, or intensity of some behaviors (eg, withdrawal responses) and suppresses other behaviors (eg, feeding). Our laboratories are developing assays to test analgesic drug candidates using measurements of pain-suppressed rather than pain-elicited behaviors. Such assays may model important aspects of clinical pain and provide a means for distinguishing true analgesics from drugs that produce motor impairment. The present study compared effects of the mu opioid analgesic morphine and the nonanalgesic neuroleptic haloperidol on intraperitoneal acetic acid-induced writhing (a pain-elicited behavior) and suppression of feeding behavior (a pain-suppressed behavior). In feeding studies, C57BL/6J mice were given access to a dish containing 8 mL Ensure ™ liquid food (0–100% in water) during daily sessions (7.5–120 min). Levels of consumption were dependent on both Ensure concentration and session duration. Intraperitoneal injection of acetic acid (0.10–0.56%) produced a time- and concentration-dependent decrease in Ensure consumption. Morphine (1 mg/kg) prevented both acid-induced writhing and acid-induced suppression of feeding, whereas the dopamine antagonist haloperidol inhibited writhing without preventing acid-induced suppression of feeding. The effects of morphine were time-dependent, selective for acid-suppressed feeding, and naltrexone-reversible. These results suggest that assays of pain-suppressed behaviors may complement assays of pain-elicited behaviors in preclinical studies of candidate analgesics. Perspective This paper presents a new preclinical strategy for assessing pain and analgesia in mice that is congruent with current methods of pain assessment in the clinic. This strategy may therefore be a useful complement to more traditional procedures for assessing pain and analgesia.

Antinociceptive and Anti-Inflammatory Properties of Daucus carota Seeds Extract

The ethanolic extract of Daucus carota seeds (DCE) was investigated for anti-inflammatory and analgesic activity at the doses [per oral (p.o.)] of 100, 200 and 400 mg/kg body weight. For evaluation of inflammation carrageenan-, histamine- and serotonin-induced paw edema served as acute models and formaldehyde-induced arthritis served as a chronic model in rats. The acetic acid-induced writhing response and formalin-induced paw licking time in the early and late phases of mice were used to assess analgesic activity. The higher doses of DCE (200 and 400 mg/kg, p.o.) were inhibiting carrageenan, histamine and serotonin-induced paw edema as well as formaldehyde-induced arthritis successfully. In addition, DCE (200 and 400 mg/kg, p.o.) significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and late phase of pain response induced by an subplantar injection of formalin in mice.