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PubMed2004

Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug.

The steam-distilled essential oil of Iranian black cumin seed (Nigella sativa L.) was investigated for its composition and analgesic and antiinflammatory properties. After oil analysis by GC/MS, 20 compounds were identified in the oil, obtained in 0.4% (v/w) yield. Among them, para-cymene (37.3%) and thymoquinone (13.7%) were the major components. Acetic acid-induced writhing, formalin and light tail flick tests were used for assessment of analgesic activity. Antiinflammatory activity was evaluated using carrageenan-induced paw oedema in rats and croton oil-induced ear oedema in mice. Black cumin seed essential oil (BCSEO) was found to produce a significant analgesic effect in acetic acid-induced writhing, formalin and light tail flick tests. Naloxone, an opioid antagonist, could not reverse the analgesic effect observed in the formalin test. Although oral administration of BCSEO at doses of 100, 200 and 400 micro L/kg did not exert a significant antiinflammatory effect in the carrageenan test, i.p. injection of the same doses significantly (p < 0.001) inhibited carrageenan-induced paw oedema. BCSEO at doses of 10 and 20 micro L/ear could also reduce croton oil-induced oedema. It seems that mechanism(s) other than opioid receptors is (are) involved in the analgesic effect of BCSEO since naloxone could not reverse this effect. Both systemic and local administration of BCSEO showed antiinflammatory activity. Thymoquinone, as one of the major components of BCSEO, probably has an important role in these pharmacological effects.

Acetic Acid↗
PubMed2004

Evaluation of the analgesic, anti-inflammatory and anti-diabetic properties of Sclerocarya birrea (A. Rich.) Hochst. stem-bark aqueous extract in mice and rats.

In order to appraise some of the ethnomedical uses of Sclerocarya birrea (A. Rich.) Hochst., subspecies caffra (Sond.) Kokwaro [family: Anacardiaceae], the present study was undertaken to investigate the analgesic, anti-inflammatory and anti-diabetic properties of the plant's stem-bark aqueous extract in experimental models of pain, inflammation and diabetes mellitus. The analgesic effect of Sclerocarya birrea stem-bark aqueous extract was evaluated in mice, while its anti-inflammatory and anti-diabetic effects were investigated in rats. Diclofenac (DIC, 100 mg/kg p. o.) and chlorpropamide (250 mg/kg p. o.) were used respectively as reference analgesic, anti-inflammatory and anti-diabetic agents for comparison. Like diclofenac (DIC, 100 mg/kg p. o.), Sclerocarya birrea stem-bark aqueous extract (SBE, 100-800 mg/kg p. o.) produced dose-dependent, significant protection (p < 0.05-0.001) against electrical heat-induced pain. The plant extract (SBE, 25-800 mg/kg p. o.) also produced dose- and time-related, sustained and significant reductions (p < 0.05-0.001) in the fresh egg albumin-induced acute inflammation of the rat hind paw oedema. However, the analgesic and anti-inflammatory effects of the plant's extract were found to be approximately 10-15 times less than that of diclofenac. In one set of experiments involving hypoglycaemic/antidiabetic evaluation of the plant's extract, graded doses of Sclerocarya birrea stem-bark aqueous extract (SBE, 25-800 mg/kg p. o.) were separately administered to groups of fasted normal and fasted diabetic rats. In another set of experiments, a single dose of the plant's aqueous extract (SBE, 800 mg/kg p. o.) was used. The hypoglycaemic effect of this single dose of Sclerocarya birrea stem-bark aqueous extract (SBE, 800 mg/kg p. o.) was compared with that of chlorpropamide (250 mg/kg p. o.) in both fasted normal and fasted streptozotocin (STZ)-treated diabetic rats. Following acute treatment, relatively moderate to high doses of Sclerocarya birrea stem-bark aqueous extract (SBE, 25-800 mg/kg p. o.) produced dose-dependent, significant reductions (p < 0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. Chlorpropamide (250 mg/kg p. o.) also produced significant reductions (p < 0.05-0.001) in the blood glucose concentrations of the fasted normal and fasted diabetic rats. Administration of the single dose of Sclerocarya birrea stem-bark aqueous extract (SBE, 800 mg/kg p. o.) significantly reduced (p < 0.01-0.001) the blood glucose levels of both fasted normal (normoglycaemic) and fasted STZ-treated, diabetic rats. The results of this experimental animal study indicate that Sclerocarya birrea stem-bark aqueous extract possesses analgesic, anti-inflammatory and hypoglycaemic properties. These experimental findings lend pharmacological support to the suggested folkloric uses of the plant's stem-bark in the management and/or control of pain, inflammatory conditions, and adult-onset, type-2 diabetes mellitus in some communities of South Africa.

Anacardiaceae↗
PubMed2006

Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats.

The present study was undertaken to investigate the analgesic, antiinflammatory and hypoglycaemic effects of Zingiber officinale dried rhizomes ethanol extract (ZOE) in mice and rats. The analgesic effect of ZOE was evaluated by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while the antiinflammatory and hypoglycaemic effects of the plant extract were investigated in rats, using fresh egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used as reference drugs for comparison. ZOE (50-800 mg/kg i.p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain in mice. The plant extract (ZOE, 50-800 mg/kg p.o.) also significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced acute inflammation, and caused dose-related, significant (p < 0.05-0.001) hypoglycaemia in normal (normoglycaemic) and diabetic rats. The findings of this experimental animal study indicate that Zingiber officinale rhizomes ethanol extract possesses analgesic, antiinflammatory and hypoglycaemic properties; and thus lend pharmacological support to folkloric, ethnomedical uses of ginger in the treatment and/or management of painful, arthritic inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural Africa communities.

Analgesics↗
PubMed1996

High mortality from urothelial carcinoma despite regular tumor screening in patients with analgesic nephropathy after renal transplantation.

Patients with end-stage renal failure due to analgesic nephropathy have an increased risk of developing a urothelial carcinoma. To determine the impact of renal transplantation on the frequency of urothelial carcinomas, we analyzed 2072 patients who underwent 2371 renal transplantation between 1968 and 1993, including 78 (3.8%) with clinically proven analgesic nephropathy. Before and after transplantation a regular tumor screening was performed in patients with analgesic nephropathy by urine cytology and abdominal sonography. In 11 of the 78 patients with analgesic nephropathy (14.1%; age 51-66 years, 40-108 months after initiation of dialysis treatment, 5-77 months after transplantation), a urothelial carcinoma of the native urinary tract, especially the kidneys, was diagnosed. Therapy comprised nephroureterectomy (n = 6), transurethral resection (n = 6) and/or cystectomy (n = 2). Seven patients died due to tumor progression 16.3 (4-33) months postoperatively and one patient died due to a perioperative complication. Despite regular tumor screening after transplantation, the diagnosis of a urothelial carcinoma was made very late, leading to a high tumor-related mortality. As a consequence, we suggest that a bilateral nephroureterectomy should be performed prophylactically in patients with proven analgesic nephropathy. In addition, a cystoscopy with lavage cytology testing of the bladder should be performed twice a year.

Acetaminophen↗
PubMed1999

[Analgesics and laxatives as risk factors for cancer in the efferent urinary tract--results of the Berlin Urothelial Carcinoma Study].

A retrospective case-control study (1990-1995), the Berlin Urothelial Cancer Study (BUS), examined analgesics and laxatives as risks for the induction of urothelial cancer in renal pelvis, ureter and bladder. Especially for renal pelvis cancer could observe substance and dose specific risk of compound analgesics. The analgesic substances Phenacetin, Paracetamol, Acetylsalicylic acid (ASA) and Pyrazolones were assessed. Besides a risk of contact laxatives (chemical or anthranoide ingredients) for urothelial cancer was found, not yet described. The highest risk shows the anthranoide plant Senna. Thus this study confirms the risk of specific analgesic ingredients and found an evidence for a new risk of contact laxatives. As both, analgesics and contact laxatives, are typical OTC--("Over the counter") products, a severe controlling is demanded and for laxatives further studies are needed.

Adult↗
PubMed1989

Longitudinal study on the consumption of analgesics, tranquilizers and hypnotics by healthy Swiss men over a 13-year period (1972-1985).

This study describes the course of medical drug consumption (analgesics, tranquilizers, and hypnotics) in 843 identical, healthy men between the ages of 20 and 33 years. In 1972-1973, 4082 randomly selected 20-year-old Swiss military recruits were interviewed with a standardized questionnaire about parental drug consumption and their own consumption of tobacco, alcohol, analgesics, tranquilizers, hypnotics, and illegal drugs. In 1979, 1658 and, in 1985, 1554 men from the original sample were asked identical and similar questions via questionnaires sent by mail. The results presented concern the 843 men who took part in all three phases. The medical drugs these men consumed most often were analgesics. However, there was a significant decrease in the number of men who took these drugs either seldom or repeatedly during the observation period (28.6% vs 21.0%; P less than 0.001). There was also a significant decrease in the proportion of men who used tranquilizers (8.7% vs 4.9%; P less than 0.01); however, the proportions of men taking hypnotics were the same in 1972-1973 and in 1985 (5.4% vs 5.2%). In the study population, repeated consumption of analgesics and/or hypnotics and/or tranquilizers at the age of 20 significantly increased the probability that the subjects would habitually consume analgesics at the age of 33. Repeated parental consumption of hypnotics increased the probability that the sons would significantly increase their consumption of hypnotics and/or tranquilizers between the ages of 20 and 33. The results are discussed against the background of other findings concerning the epidemiology of drug consumption.

Adult↗
PubMed1990

Peripheral and central opioid activity in the analgesic potency of morphine.

The role of neural histamine in morphine-analgesia and in morphine-induced potentiation of stress analgesia was studied. Pretreatment of rats with alpha-fluoromethylhistidine (alpha-FMH) (200 micrograms i.c.v./rat; daily for five days) increased the analgesic potency of morphine, centrally or peripherally injected, in the tail-flick assay. This increase was significantly blocked by i.c.v. or i.p. beta-funaltrexamine (beta-FNA) a mu selective irreversible opioid receptor antagonist, whereas i.c.v. injected naltrexone did not block the increased analgesic potency of the i.c.v. morphine. Rats subjected to cold-restrained stress (60 min at 4 degrees C) showed increased tail-flick latency, compared to the unstressed group. The analgesic potency of morphine was significantly greater in rats subjected to restraint with respect to unstressed rats. However, the inhibition of histamine biosynthesis by alpha-FMH significantly reduced cold-restraint analgesia in controls, and also inhibited the analgesic efficacy of the opiate. These results indicate that neural histamine may be responsible for pain response modifications observed in rats subjected to cold-restraint conditions, and of morphine-potentiation of stress analgesia. The data also suggest a close association between increased analgesic potency of morphine and inhibition of histaminergic effects, possibly implying a functional supersensitivity and an increase in opioid receptors.

Analgesics↗
PubMedDate not supplied

[Social histories of female abusers of phenacetin-containing analgesics].

The abuse of analgesics is common in the Swiss population. In a field study social und psychological investigations with 600 women ingesting analgesics and 600 women not taking analgesics are made. In a preliminary interpretation of 80 interviews the women ingesting analgesics differ only in a few points from the control group: 1. In the study group a greater number women has children, however on the average a lower number than the control group 2. The children of the women ingesting analgesics are more often taken care of outside their own home. 3. As an overwhelming event in life the loss of one or both parents was often mentioned. 4. Questions asked with regard to depressive symptoms were similar for both groups.

Analgesics↗
PubMedDate not supplied

The effectiveness of analgesics in traumatic injuries of the extremities.

In this study, the effectiveness of different analgesics was investigated in patients who presented to the emergency room with traumatic injuries or fractures of the extremities. We observed 100 patients (42 male, 58 female) who presented to the Konya State Hospital emergency service with isolated traumatic injuries of the extremities. We used different analgesics intravenously or intramuscularly in those patients with a high or moderate level of pain according to a visual analog pain scale. Patient pain levels were assessed 15, 30, and 45 minutes after administration of the analgesics. Metamizole sodium 1 g IV was used in 36 patients and diclofenac sodium 75 mg IM was given to 40 patients; tramadol hydrochloride 100 mg IV was administered to 24 patients. Pain became less severe after 15 minutes in 92% of patients who received tramadol IV; pain became less severe after 30 minutes in 72% of those who received metamizole IV. In contrast, pain became less severe after 45 minutes in 65% of patients who received diclofenac IM. Tramadol was the most effective analgesic and was also more effective earlier than the other analgesics tested.

Adolescent↗
PubMed2004

Analgesic effect of intra-articular ketorolac in knee arthroscopy: comparison of morphine and bupivacaine.

This prospective study assessed the postoperative analgesic effect of intra-articular ketorolac, morphine, and bupivacaine during arthroscopic outpatient partial meniscectomy. Group 1 patients (n=20) received postoperative injection of 60 mg intra-articular ketorolac, group 2 patients (n=20) 10 cc intra-articular bupivacaine 0.25%, group 3 patients (n=20) 1 mg intra-articular morphine diluted in 10 cc saline, and group 4 patients (n=20, controls) only 10 cc saline. We evaluated the postoperative analgesic effect (period measured from the end of the surgery until further analgesia was demanded), the level of postoperative pain (by visual analog scale 1, 2, 3, 12, and 24 h after surgery), and the need for additional pain medication (during the first 24 h after surgery). The best analgesic effect was in patients treated with intra-articular ketorolac, and this was statistically significant in: postoperative analgesic effect and the need for additional pain medication immediately after surgery, and after 24 h. No complications were found related to the intra-articular treatment. We conclude that 60 mg intra-articular ketorolac provides better analgesic effect than 10 cc intra-articular bupivacaine 0.25% or 1 mg intra-articular morphine.

Analgesics, Opioid↗
PubMed2002

Guaifenesin enhances the analgesic potency of paracetamol in mice.

AIM OF INVESTIGATION: Guaifenesin is used as an expectorant and it has been reported to possess muscle relaxant and sedative activity. Guaifenesin has been used as a component of composite OTC analgesics containing paracetamol for many years. The aim of our study was to ascertain effects of guaifenesin on paracetamol analgesic activity and locomotor performance. METHODS: Antinociceptive efficacy was tested in mice using an acetic acid (0.7%) writhing test. Locomotor performance was tested in rota-rod test and activity cage. All drugs were given orally and tested in mice. RESULTS: In combination with a subeffective dose of guaifenesin (200 mg/kg), the ED(50) for paracetamol in the writhing test was significantly lower (82.2 mg/kg) than that of paracetamol administered alone (233.7 mg/kg). Guaifenesin alone did not show an analgesic effect. Guaifenesin did not produce statistically significant locomotor impairment in the rota-rod test at doses enhancing analgesic activity of paracetamol, although there was a trend for decreased locomotor activity in activity cage. CONCLUSION: The present results indicate that guaifenesin may enhance analgesic activity of paracetamol.

Acetaminophen↗
PubMed2003

Neonatal ethanol exposure produces a hyperalgesia that extends into adolescence, and is associated with increased analgesic and rewarding properties of nicotine in rats.

RATIONALE: Drug exposure during CNS development may alter subsequent dependence liability. We postulated that early alcohol exposure might produce persistent alterations in responses to noxious stimuli. Because relief of physical discomfort may be negatively reinforcing, changes in responses to noxious stimuli produced by early alcohol exposure may increase the rewarding properties of nicotine, a potent analgesic. Such factors may contribute to the high level of alcohol and nicotine co-abuse in humans. OBJECTIVES: The purpose of this study was to determine whether neonatal ethanol exposure in rats altered responses to noxious stimuli, and whether nicotine would then be more rewarding to the alcohol-exposed offspring, perhaps via its analgesic actions. METHODS: Neonatal rats received ethanol by gavage (5.0 or 6.5 g/kg) on postnatal days (PND) 9-13. An iso-caloric control group was also included. Rats were then tested to assess responsiveness to a mild noxious heat stimulus, as measured in the tail-flick assay (PND 14 and PND 28), for their response to acute analgesic injections of either nicotine or ethanol (PND 28), and for nicotine induced conditioned place preference (CPP) (PND 36). RESULTS: Neonatal ethanol exposure produced hyperalgesia during the first 24 h after alcohol withdrawal (PND 14) that continued through PND 28. The analgesic effects of 12.5 microg/kg nicotine were enhanced approximately 2-fold in adolescent rats with previous ethanol histories, relative to controls. These ethanol-exposed rats also showed a significant CPP to nicotine, whereas controls showed no CPP. CONCLUSIONS: Persistent decreases in tail-flick response latencies suggestive of hyperalgesia were observed following neonatal ethanol exposure in the rat. These changes were accompanied by increases in the analgesic and place-conditioning effects of nicotine in adolescence. If similar effects occur in humans, prenatal alcohol exposure may play a role in an increased risk for the rewarding effects and dependence liability of nicotine later in life.

Analgesics↗
PubMed2004

Trends in consumption of opioid analgesics in Slovak Republic during 1998-2002.

OBJECTIVE: To describe the patterns of consumption in an opioid analgesic group in Slovakia between 1998 and 2002, to determine prescription habits, and to compare the results with those from selected countries. METHODS: A drug utilization study using WHO methodology [Anatomical-Therapeutic-Chemical classification/defined daily doses (ATC/DDD)] was made. The wholesale data from the State Institute of Drug Control in the Slovak Republic and drug safety reports from the National Centre for Supervision of Adverse Drug Reaction were collected. Utilization was calculated as the DDDs per 1000 inhabitants per day. RESULTS: Consumption of opioid analgesics (ATC class N02AA-N02AX) in Slovakia was still growing during the study with dominance of tramadol. In comparison with other countries in 2001, consumption of morphine (as a representative of analyzed ATC class) in Slovakia (0.17 DDD/1000 inhabitants per day) is still very low, in contrast with Denmark, Austria or Canada (1.80, 1.61 and 1.58 DDD/1000 inhabitants per day, respectively). The collected safety reports contained only a few reported adverse reactions to the opioid analgesics. CONCLUSION: Despite recent increases, the consumption of opioid analgesics in the Slovak republic remains low. We have tried to present an overall picture of prescription of opioid analgesics in Slovakia and to focus attention on this topic.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

Targeted topical peripheral analgesics in the management of pain.

The term "targeted peripheral analgesics" has been developed to describe analgesics whose mechanism of action appears to be primarily through reducing pain transmission within the peripheral nervous system. Key differences between targeted peripheral and systemic analgesics and the difference between topical and transdermal analgesics are discussed. A review of the clinical conditions that have reportedly responded to targeted peripheral analgesics is described in detail in this article.

Administration, Topical↗
PubMed2004

Targeted peripheral analgesics therapy for neuropathic pain.

The term targeted peripheral analgesics has been suggested to describe analgesics with a mechanism of action that appears to be primarily through reducing pain transmission within the peripheral nervous system. Key differences between targeted peripheral (topical) and systemic analgesics and the difference between topical and transdermal analgesics are discussed in this article. A review of the clinical conditions, which have been reported to respond to targeted peripheral analgesics, also is described in detail.

Administration, Cutaneous↗
PubMed1989

The refractory headache patient--II. High medication consumption (analgesic rebound) headache.

'Analgesic rebound headache' is identified by habituation of an individual to pain reducing medication, the exacerbation of headache pain a few hours after medication consumption and a marked increase in headache frequency and intensity for several weeks after medication is discontinued. We describe three studies undertaken to clarify the existence and characteristics of this proposed headache syndrome. In Study 1 we compared a group of headache sufferers who consume large amounts of analgesic medications to headache sufferers who did not consume excessive analgesics. It was found that the two groups did not differ on age, duration of headache problem or gender. However, the groups did differ on subjective headache pain (with the high medicators experiencing more headache pain than low medicators) and diagnosis (with high medicators being more likely to have a muscle contraction component to their headaches). In an analysis of drug use within the high medication group, it was found that 91% were taking some kind of analgesic and that a majority (84%) were taking more than one type of medication. In Study 2 we found that the group of high medicators were not as successful in reducing headache activity as a result of a self-regulatory behavioral treatment as the matched controls. Furthermore, there was a direct relationship between reduction and treatment success in the high medication consuming population. Lastly, in Study 3 we examined the current psychological functioning of the two groups; no differences were found between the two groups indicating the lack of 'addictive' personality characteristics as an explanation for the high medicating population. These findings all support the existence of a sub-population of headache sufferers who consume excessive amounts of analgesic medication and who are relatively refractory to behavioral treatment.

Adult↗
PubMed1986

Evaluation of the analgesic effects of capsaicin using a new rat model for tonic pain.

An animal model for tonic pain has been produced by means of injecting monosodium urate crystals into a knee joint of rat hind paws in order to evaluate the analgesic effects of various drugs and analgesic methods and to elucidate the physiology of tonic pain. This model allows for stable and long-term behavioural changes due to tonic pain followed by complete recovery without tissue damages. It is advantageous in allowing for objective and quantitative evaluation of the effects of analgesics and should prove useful in research on pain and the development of pain therapy techniques. Using this model, the analgesic effects of capsaicin was evaluated when administered to the neonatal rat or locally to peripheral nerves. In both cases, significant analgesic effects were obtained.

Analgesics↗
PubMed1988

Analgesic effects of the putative FSH-suppressing gonadal steroid, 3 alpha-hydroxy-4-pregnen-20-one: possible modes of action.

The effects of intracerebroventricular (i.c.v.) administrations of the putative follicle stimulating hormone (FSH) suppressing gonadal steroid, 3 alpha-hydroxy-4-pregnen-20-one (3A4P) on the nociceptive responses of male mice were examined. This allylic steroid elicited significant, dose-dependent (0.001-1.0 micrograms) analgesic responses for 90-150 min after injection. These analgesic effects of 3A4P were stereospecific, the stereoisomer, 3 beta-hydroxy-4-pregnen-20-one (3B4P) failing to affect the nociceptive responses. The analgesic effects of 3A4P were blocked by peripheral administrations of the GABA antagonists, bicuculline and picrotoxin, and reduced by the benzodiazepine antagonist, Ro 15-1788. The exogenous opiate antagonist, naloxone, and the putative endogenous opioid antagonist, Tyr-MIF-1 (Pro-Leu-Gly-amide), also reduced 3A4P-induced analgesia, while i.c.v. administration of 3A4P (0.001 and 0.01 micrograms) itself attenuated the analgesic effects arising from peripheral administrations of opiate receptor agonist, morphine. In addition, the calcium channel antagonists, nifedipine and verapamil, enhanced 3A4P-induced analgesia but had no evident effects on the actions of 3B4P. These results suggest that the central analgesic effects of the FSH-suppressing steroid, 3A4P, arise via benzodiazepine--GABA--opiate mechanisms and calcium channels. These findings also suggest possible central modes of action whereby 3A4P may elicit selective suppression of FSH.

20-alpha-Dihydroprogesterone↗