allopurinol and Pain

Gout is currently the most common form of inflammatory arthritis in men. The overall incidence of gout has increased rapidly in the past 20 years. Clinicians in all fields are likely to experience a patient with acute gout in their career. Uncontrolled gout and hyperuricemia can lead to joint destruction and significant morbidity. Fortunately, these diseases can be readily treated and long-term sequelae can be prevented. Recent advances in understanding the role of the innate immune system in acute gout have provided new treatment options. This article addresses the epidemiology, inflammatory pathophysiology, pain management techniques (including recent advances), and treatment of the underlying disease itself.

Topics: Adrenal Cortex Hormones; Allopurinol; Animals; Disease Management; Gout; Humans; Pain

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used in the treatment of hyperuricemia and gout. Because it is well known that purines exert multiple affects on pain transmission, we hypothesized that the inhibition of xanthine oxidase by allopurinol could be a valid strategy to treat pain in humans. This study aimed to compare the analgesic efficacy of oral allopurinol versus placebo as an adjuvant therapy in patients displaying fibromyalgia.. This randomized, double-blinded, placebo-controlled study included 60 women with the diagnosis of fibromyalgia. Patients were randomly assigned to receive either oral allopurinol 300 mg (n = 31) or placebo (n = 29) twice daily during 30 days. The patients were submitted to evaluation for pain sensitivity, anxiety, depression, and functional status before treatment, and 15 and 30 days thereafter.. Oral administration of allopurinol 300 mg twice daily was ineffective in improving pain scores measured by several tools up to 30 days of treatment (P > 0.05). Additionally, no significant effects of allopurinol over anxiety, depressive symptoms, and functional status of fibromyalgia patients were observed in the present study.. Although previous findings indicated that allopurinol could present intrinsic analgesic effects in both animals and humans, this study showed no benefit of the use of oral allopurinol as an adjuvant strategy during 30 days in women displaying fibromyalgia. However, considering previous promising results, new prospective studies are still valid to further investigate allopurinol and more selective purine derivatives in the management of pain syndromes.

Topics: Allopurinol; Animals; Double-Blind Method; Female; Fibromyalgia; Gout Suppressants; Humans; Pain; Prospective Studies; Treatment Outcome; Uric Acid

L-carnitine L-tartrate (LCLT) supplementation beneficially affects markers of postexercise metabolic stress and muscle damage. However, to date, no study has determined the dose response of LCLT to elicit such responses. Therefore, the purpose of this study was to determine the effects of different doses of LCLT on criterion variables previously shown to be responsive to LCLT supplementation. Eight healthy men (22 +/- 3 y, 174 +/- 5 cm, 83.0 +/- 15.3 kg) were supplemented with 0 g, 1 g, and 2 g of LCLT for 3 weeks and then performed a bout of resistance exercise (5 sets of 15-20 repetition maximum with a 2-min rest between sets) with associated blood draws. This procedure was performed in a balanced, randomized, repeated measures design. Serum carnitine concentrations increased (p < or = 0.05) following the 1 g and 2 g doses, with the 2-g dose providing the highest carnitine concentrations. The 1- and 2-g doses reduced postexercise serum hypoxanthine, serum xanthine oxidase, serum myoglobin, and perceived muscle soreness. In conclusion, both the 1- and 2-g doses were effective in mediating various markers of metabolic stress and of muscle soreness. Use of LCLT appears to attenuate metabolic stress and the hypoxic chain of events leading to muscle damage after exercise.

Topics: Adult; Analysis of Variance; Area Under Curve; Biomarkers; Blood Glucose; Carnitine; Cross-Over Studies; Dietary Supplements; Dose-Response Relationship, Drug; Exercise Test; Hand Strength; Humans; Hypoxanthine; Insulin-Like Growth Factor Binding Protein 3; Lactates; Male; Myoglobin; Pain; Physical Education and Training; Tartrates; Xanthine Oxidase

A dosage of 300 mg/d of allopurinol was not effective in reducing pain or improving activities of daily living in chronic pancreatitis.. Allopurinol prevents the generation of oxygen-derived free radicals by inhibiting xanthine oxidase. The purpose of this study was to determine whether allopurinol is effective in reducing pain of chronic pancreatitis.. Thirteen patients with chronic pancreatitis who were experiencing abdominal pain requiring medication at least three times each week entered a randomized, double-blind, two-period crossover clinical trial. Patients evaluated their pain daily using a categorical pain intensity scale, numeric pain intensity scale, and a visual analog scale, and weekly completed a McGill Pain Questionnaire and activities of daily living (ADL) questionnaire.. The mean baseline score of pain was approx 50% of most severe pain in all scoring systems. There was no significant decrease in pain associated with allopurinol compared to the placebo (p = 0.24-0.75). In addition, there was no benefit in terms of ADL score associated with allopurinol compared with placebo (p = 0.32). Mean uric acid level was decreased by 1.15 mg/dL while patients were taking allopurinol, compared to when they were taking placebo (p = 0.007).

Topics: Abdominal Pain; Activities of Daily Living; Adult; Allopurinol; Ankle; Blood Cell Count; Chronic Disease; Cross-Over Studies; Diarrhea; Double-Blind Method; Enzyme Inhibitors; Exanthema; Face; Female; Humans; Joints; Liver Function Tests; Male; Middle Aged; Nausea; Pain; Pain Measurement; Pancreatitis; Placebos; Prospective Studies; Uric Acid; Vomiting

Topics: Adult; Allopurinol; Dimethyl Sulfoxide; Drug Therapy, Combination; Humans; Male; Middle Aged; Pain; Pancreatitis

Chinese patients with arthralgia during treatment with an antituberculosis regimen containing pyrazinamide were allocated at random to 3 anti-arthralgia treatment series in a controlled double-blind study. One series (18 patients) received soluble aspirin 2.4 g daily, the second (23 patients) allopurinol 200 mg daily, and the third (19 patients) placebo only, for 8 weeks. The response was assessed both by independent assessors and by the patients themselves using a diary card. The serum uric acid concentration was measured before and during anti-arthralgia treatment. The joints most commonly affected were the shoulders, the knees and the fingers, and symptoms and signs were in general neither severe nor protracted. For most of the patients in all 3 series the joint symptoms and signs improved during the 8 weeks, but a higher proportion of patients in the aspirin and placebo series than in the allopurinol series experienced improvement, this being most rapid in the aspirin series. Only in the aspirin series was the mean serum uric acid concentration lower during treatment than before it, and this effect was related to the dose in mg per kg. It is concluded that the arthralgia was often self-limiting, that aspirin had a small beneficial effect, that allopurinol, in the dosage studied, may have had a slightly deleterious effect, but that it would be worth studying larger dosages of allopurinol because the dosage studied did not affect the serum uric acid concentration.

Topics: Adolescent; Adult; Aged; Allopurinol; Aspirin; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Joint Diseases; Male; Middle Aged; Pain; Pyrazinamide; Random Allocation; Time Factors; Tuberculosis, Pulmonary; Uric Acid

Granulocyte colony-stimulating factors (G-CSF) are utilized both in the treatment and prophylaxis of chemotherapy-induced neutropenia. Lipegfilgrastim is a long-acting G-CSF. Albeit it provides ease of administration compared to short-acting GCSFs, some lipegfilgrastim-related adverse events may occur. Bone pain, widespread body pain, and feeling of fever are among common adverse effects, while rare but more serious adverse effects such as leukocytosis, spleen rupture, interstitial pneumonia, acute respiratory distress syndrome, capillary leak syndrome, hypokalemia, and glomerulonephritis may occur as well.. We reported a case of hyperleukocytosis that developed due to prophylactic administration of lipegfilgrastim following the first course of neoadjuvant pertuzumab (840-420 mg), trastuzumab (8-6mg/kg), and docetaxel (75 mg/m2) in a 45-year-old female patient with a diagnosis of breast invasive ductal carcinoma. The patient, who presented with weakness, loss of appetite, and oral intake disorder, had elevated white blood cell (WBC), lactate dehydrogenase (LDH), and uric acid levels in her test results. Peripheral smear (PS) had a left shift.. Intravenous 0.9% NaCl and peroral allopurinol were started to be administered to the patient. On the ninth day of hospitalization, the patient's clinical manifestation improved, and her WBC, LDH, uric acid, and PS returned to normal. Besides, the progression to tumor lysis syndrome (TLS) was prevented by appropriate hydration and allopurinol treatment. In subsequent chemotherapies (CTs), lipegfilgrastim was discontinued and filgrastim was started. The patient whose hyperleukocytosis did not recur was operated on following neoadjuvant CT. The patient's routine follow-up continues without any problems.. Although lipegfilgrastim-induced hyperleukocytosis has not been reported in the literature, it should be borne in mind that hyperleukocytosis and related complications may occur, as in our case.

Topics: Allopurinol; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Middle Aged; Pain; Polyethylene Glycols; Uric Acid

Chinese herbal medicinal plants, Euonymus laxiflorus (EL), Rubia lanceolata (RL) and Gardenia jasminoides (GJ), have been used wildly to treat arthritis and gout in Taiwan for decades. To understand the beneficial effects of these three plants, their xanthine oxidase (XO) inhibitory activity in vitro and hypouricaemic activity in vivo were investigated. Our results suggested that methanol extracts were better than water extracts for inhibition of XO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, except the water extract of GJ, which exhibited the strongest radical scavenging effect. In animal study, the serum urate level was significantly decreased after oral administration of higher dose (0.39g/kg) methanol extract of the mixture of three plants (ERG). In addition, methanol extract of ERG reduced the pain reaction time in the second phase of formalin induced pain. The results provide useful information on the pharmacological activities of these plants for the potential in treating hyperuricemia.

Topics: Animals; Disease Models, Animal; Euonymus; Formaldehyde; Gardenia; Gout; Hyperuricemia; Nociception; Pain; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Rubia; Taiwan; Toxicity Tests; Uric Acid; Xanthine Oxidase

Inhibition of xanthine oxidase by allopurinol increases hypoxanthine and xanthine, which are converted to purines, including the inhibitory neuromodulator adenosine.. We aimed to investigate the antinociceptive effects of allopurinol in thermal and chemical pain models in mice and to evaluate its possible antinociceptive mechanism by using selective adenosine receptors A1, A2A antagonists in mice.. Sixty four adult male mice were used. Mice received an intraperitoneal injection of vehicle or allopurinol (50-200 mg/kg). Assessment of antinociceptive effects and locomotor activity were performed in three models of acute pain; a thermal model and two chemical model.. Allopurinol presented dose-dependent antinociceptive effects in all models with no obvious motor deficits. The opioid antagonist naloxone did not reverse these effects. The selective A1 antagonist, DPCPX, and the selective A2A antagonist, ZM241385, completely prevented allopurinol-induced antinociception.. Allopurinol-induced antinociception may be related to adenosine accumulation. Allopurinol seems to be well tolerated with no locomotor side effects at high doses and it may be useful to treat pain syndromes.

Topics: Adenosine A1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; Allopurinol; Analgesics; Animals; Capsaicin; Hot Temperature; Male; Mice; Motor Activity; Pain; Pain Measurement; Postural Balance; Psychomotor Performance; Receptor, Adenosine A2A; Receptors, Purinergic P1

Local cutaneous heating causes vasodilation as an initial first peak, a nadir, and increase to plateau. Reactive oxygen species (ROS) modulate the heat plateau in healthy controls. The initial peak, due to C-fiber nociceptor-mediated axon reflexes, is blunted with local anesthetics and may serve as a surrogate for the cutaneous response to peripheral heat. Chronic fatigue syndrome (CFS) subjects report increased perception of pain. To determine the role of ROS in this neurally mediated response, we evaluated changes in cutaneous blood flow from local heat in nine CFS subjects (16-22 yr) compared with eight healthy controls (18-26 yr). We heated skin to 42°C and measured local blood flow as a percentage of maximum cutaneous vascular conductance (%CVC(max)). Although CFS subjects had significantly lower baseline flow [8.75 ± 0.56 vs. 12.27 ± 1.07 (%CVC(max), CFS vs. control)], there were no differences between groups to local heat. We then remeasured this with apocynin to inhibit NADPH oxidase, allopurinol to inhibit xanthine oxidase, tempol to inhibit superoxide, and ebselen to reduce H(2)O(2). Apocynin significantly increased baseline blood flow (before heat, 14.91 ± 2.21 vs. 8.75 ± 1.66) and the first heat peak (69.33 ± 3.36 vs. 59.75 ± 2.75). Allopurinol and ebselen only enhanced the first heat peaks (71.55 ± 2.48 vs. 61.72 ± 2.01 and 76.55 ± 5.21 vs. 58.56 ± 3.66, respectively). Tempol had no effect on local heating. None of these agents changed the response to local heat in control subjects. Thus the response to heat may be altered by local levels of ROS, particularly H(2)O(2) in CFS subjects, and may be related to their hyperesthesia/hyperalgesia.

Topics: Acetophenones; Administration, Cutaneous; Adolescent; Adult; Allopurinol; Antioxidants; Axons; Cyclic N-Oxides; Fatigue Syndrome, Chronic; Female; Hot Temperature; Humans; Hydrogen Peroxide; Male; NADPH Oxidases; Nerve Fibers, Unmyelinated; Nociceptors; Pain; Reactive Oxygen Species; Reflex; Regional Blood Flow; Skin; Spin Labels; Superoxides; Vasodilation; Xanthine Oxidase; Young Adult

Aristotelia chilensis leaves (Elaeocarpaceae) are used in Chilean folk medicine to treat pain and inflammation. A bioguided study was carried out on serial extracts (hexane, dichloromethane, methanol, aqueous extract (INFU) and a crude mixture of alkaloids (ALK-MIX). All extracts were evaluated for (1) topical administration against both arachidonic acid and 12-deoxyphorbol-13-decanoate (TPA)-induced inflammation in mice and (2) per-os administration against inflammation by λ-carrageenan-induced paw oedema in guinea-pigs and (3) topical analgesia in tail flick and formalin models and per-os writhing test in mice.. Greater anti-inflammatory effects were obtained against TPA with dichloromethane extract and methanol extract (63.9 and 66.0%, respectively). INFU showed the most potent effect (56.2%) against arachidonic acid. Greater effects were obtained in the writhing test with hexane and dichloromethane extracts (89.2% both). In the topical analgesia models, all the extracts and ALK-MIX were active with exception of the hexane extract in the formalin assay. In tail flick test, ALK-MIX and the methanol extract were the most active (58.2 and 55.2%, respectively). In relation to the tail formalin assay, the methanol extract (74.1%) was the most active. Concerning antioxidant activity, both INFU and the methanol extract were the most active either in the inhibition of xanthine oxidase (52.9 and 62.7%, respectively) or in the DPPH free radical scavenging activity (EC50 (concentration that produced 50% of activity) = 12.1 and 9.7 µg/ml, respectively).. Aristoteline, aristone, serratoline and hobartinol were isolated from ALK-MIX. Ursolic acid, friedelin and quercetin 5,3'-dimethyl ether were present in the dichloromethane extract while quercetin 3-O-β-D-glucoside and kaempferol were present in the methanol extract. From INFU were isolated protopine, aristoteline and caffeic and ferulic acids.. The effects of A. chilensis are herein demonstrated, validating its use in traditional medicine. Protopine is reported for the first time in Elaeocarpaceae.

Topics: Administration, Topical; Alkaloids; Analgesia; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Behavior, Animal; Biphenyl Compounds; Carrageenan; Chile; Edema; Elaeocarpaceae; Female; Formaldehyde; Guinea Pigs; Inflammation; Male; Medicine, Traditional; Mice; Mice, Inbred Strains; Pain; Phorbol Esters; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Xanthine Oxidase

Gout and pain are synonymous, and a study in this issue of the BJP reports a novel anti-nociceptive effect of allopurinol, the drug most commonly used to treat gout. Allopurinol works by inhibiting xanthine oxidase (XO), the enzyme responsible for converting hypoxanthine to uric acid which is deposited as crystals in the joints of gout sufferers. Hypoxanthine is a metabolite of, and a possible precursor to, adenosine. Schmidt et al., find that acute inhibition of XO with allopurinol produces a modest adenosine A(1) receptor-mediated anti-nociceptive effect in common tests of chemical and thermal nociception in mice. A concomitant increase in cerebrospinal fluid levels of adenosine supports their hypothesis that inhibiting XO increases adenosine levels via salvage from hypoxanthine. Elevating endogenous adenosine levels by inhibiting metabolism is a well-established strategy for producing anti-nociception in many preclinical models, but inhibiting XO is likely to be particularly beneficial in some chronic pain states because of the pro-nociceptive reactive oxygen species that are produced by XO activity. Thus, allopurinol may have unexpected benefits in pain associated with chronic inflammation, diabetes and vascular dysfunction.

Topics: Adenosine; Adenosine A1 Receptor Agonists; Allopurinol; Analgesics; Animals; Gout; Mice; Pain; Reactive Oxygen Species; Xanthine Oxidase

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase, used primarily in the treatment of hyperuricemia and gout. It is well known that purines exert multiple effects on pain transmission. We hypothesized that the inhibition of xanthine oxidase by allopurinol, thereby reducing purine degradation, could be a valid strategy to enhance purinergic activity. The aim of this study was to investigate the anti-nociceptive profile of allopurinol on chemical and thermal pain models in mice.. Mice received an intraperitoneal (i.p.) injection of vehicle (Tween 10%) or allopurinol (10-400 mg kg(-1)). Anti-nociceptive effects were measured with intraplantar capsaicin, intraplantar glutamate, tail-flick or hot-plate tests.. Allopurinol presented dose-dependent anti-nociceptive effects in all models. The opioid antagonist naloxone did not affect these anti-nociceptive effects. The non-selective adenosine-receptor antagonist caffeine and the selective A(1) adenosine-receptor antagonist, DPCPX, but not the selective A(2A) adenosine-receptor antagonist, SCH58261, completely prevented allopurinol-induced anti-nociception. No obvious motor deficits were produced by allopurinol, at doses up to 200 mg kg(-1). Allopurinol also caused an increase in cerebrospinal fluid levels of purines, including the nucleosides adenosine and guanosine, and decreased cerebrospinal fluid concentration of uric acid.. Allopurinol-induced anti-nociception may be related to adenosine accumulation. Allopurinol is an old and extensively used compound and seems to be well tolerated with no obvious central nervous system toxic effects at high doses. This drug may be useful to treat pain syndromes in humans.

Topics: Adenosine; Adenosine A1 Receptor Agonists; Adenosine A1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; Allopurinol; Analgesics; Animals; Capsaicin; Dose-Response Relationship, Drug; Glutamic Acid; Hot Temperature; Injections, Intraperitoneal; Male; Mice; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Pyrimidines; Triazoles; Uric Acid; Xanthine Oxidase; Xanthines

An emerging theme in the study of the pathophysiology of persistent pain is the role of reactive oxygen species (ROS). In the present study, we examined the hypothesis that the exogenous supply of antioxidant drugs during peri-reperfusion would attenuate pain induced by ischemia/reperfusion (IR) injury. We investigated the analgesic effects of three antioxidants administered during peri-reperfusion using an animal model of complex regional pain syndrome-type I consisting of chronic post-ischemia pain (CPIP) of the hind paw.. Application of a tight-fitting tourniquet for a period of 3 h produced CPIP in male Sprague-Dawley rats. Low-dose allopurinol (4 mg/kg), high-dose allopurinol (40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), or SOD (4000 U/kg)+L-NAME (10 mg/kg) was administered intraperitoneally just after tourniquet application and at 1 and 2 days after reperfusion for 3 days. The effects of antioxidants in rats were investigated using mechanical and cold stimuli. Each group consisted of seven rats.. Allopurinol caused significant alleviation in mechanical and cold allodynia for a period of 4 weeks in rats with CPIP. Both SOD and L-NAME, which were used to investigate the roles of superoxide (O2(-)) and nitric oxide (NO) in pain, also attenuated neuropathic-like pain symptoms in rats for 4 weeks.. Our findings suggest that O2(-) and NO mediate IR injury-induced chronic pain, and that ROS scavengers administered during the peri-reperfusion period have long-term analgesic effects.

Topics: Allopurinol; Animals; Chronic Disease; Cold Temperature; Enzyme Inhibitors; Free Radical Scavengers; Ischemia; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pain; Physical Stimulation; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Superoxide Dismutase; Xanthine Oxidase

Several putative sources of reactive oxygen species could potentially contribute to diabetic neuropathy and vasculopathy. The aim was to assess the involvement of elevated xanthine oxidase activity. After 6 weeks of streptozotocin-diabetes, groups of rats were given 2 weeks of high-dose allopurinol treatment (50 and 250 mg/kg) to gauge the effect of maximal blockade of xanthine oxidase. In the final experiments, rats were subjected to sensory testing and, under butabarbital anaesthesia, measurements were made on nerve conduction velocities and neural tissue blood flow estimated by hydrogen clearance microelectrode polarography. Further groups were used to study detailed responses of the isolated mesenteric vascular bed after 4 weeks of diabetes and allopurinol (150 mg/kg) treatment. Diabetes caused 20% and 14% reduction in motor and sensory conduction velocity, which were 78% and 81% corrected by allopurinol treatment respectively, both doses giving similar results. Diabetic rats showed tactile allodynia and thermal hyperalgesia, which were completely corrected by allopurinol, whereas mechanical hyperalgesia was only 45% ameliorated. Sciatic nerve and superior cervical ganglion blood flow was halved by diabetes and allopurinol corrected this by approximately 63%. Mesenteric endothelium-dependent vascular responses to acetylcholine, which depend upon nitric oxide and endothelium derived hyperpolarizing factor, were attenuated by diabetes. Allopurinol treatment gave approximately 50% protection for both components. Thus, xanthine oxidase is an important source of reactive oxygen species that contributes to neurovascular dysfunction in experimental diabetes. Inhibition of xanthine oxidase could be a potential therapeutic approach to diabetic neuropathy and vasculopathy.

Topics: Acetylcholine; Allopurinol; Animals; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Disease Models, Animal; Enzyme Inhibitors; Ganglia, Autonomic; Hyperalgesia; Male; Mesenteric Artery, Superior; Neural Conduction; Pain; Polarography; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Regional Blood Flow; Sciatic Nerve; Xanthine Oxidase

Using a reversible chronic constriction injury (CCI) model of neuropathic pain, we previously demonstrated that changes in thermal hyperalgesia correlate with the changes in peripheral microvascular blood flow in the affected paw, and that recovery can be assessed by normalization of both behavioral and vascular responses. Using the same model, this study examined age-related changes in recovery after nerve injury and the involvement of free radicals and nitric oxide (NO) in these changes. Four loose, nonconstrictive ligatures were applied to the sciatic nerve in the right, mid-thigh region of young and old (3 and 24 months) Sprague Dawley rats. All rats were monitored weekly (for 8-10 weeks) for their thermal threshold using a 46 degrees C water bath and some groups were used to examine endothelial and smooth muscle-dependent microvascular responses to substance P (SP) and sodium nitroprusside (SNP), respectively. These substances were perfused over the base of blisters raised on the footpad innervated by the injured nerve. Free radical activity in the sciatic nerve was assessed by measuring the activity of xanthine oxidase (XO) and lipid hydroperoxides (LPO). Young rats showed signs of recovery (reduction in thermal hyperalgesia and improvement of peripheral microvascular blood flow) from the fifth week. No signs of recovery were observed in old rats for 8 weeks, with some reduction in thermal hyperalgesia observed by weeks 9 and 10. XO activity was significantly higher in young injured nerves compared to sham (400%) and was even significantly greater in old injured nerves (680%). Similarly, old injured nerves showed 300% increase in LPO levels compared to sham. The role of reactive oxygen species (ROS) in delayed recovery in old rats was examined using the antioxidant tirilazad mesylate. Tirilazad (20 mg/kg) was injected intramuscularly (im) in the mid-thigh region starting on day 1 post CCI, (early treatment) or day 7 (late treatment). Levels of LPO in the injured sciatic nerves were significantly reduced using either early or late treatment, however tirilazad had opposing effects on recovery, prolonging or alleviating thermal hyperalgesia, respectively. The role of neuronal nitric oxide (nNO) was then examined using the specific neuronal nitric oxide synthase (nNOS) inhibitor, 3-bromo-7-nitroindazole (3Br-7NI) (10 mg/kg). 3Br-7NI resulted in a significant alleviation of thermal hyperalgesia with improvement in the vascular responses from weeks 5 and

Topics: Aging; Animals; Antioxidants; Chronic Disease; Constriction, Pathologic; Free Radicals; Hot Temperature; Hyperalgesia; Lipid Peroxides; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Pain; Pregnatrienes; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sciatic Nerve; Xanthine Oxidase

Topics: 5-Hydroxytryptophan; Allopurinol; Animals; Brain; Enzyme Inhibitors; Nialamide; Pain; Rats; Rats, Wistar; Serotonin; Transcutaneous Electric Nerve Stimulation; Tryptophan

The administration to rats of tryptophan (CAS 73-22-3) in high dosage causes a significant increase in pain threshold values. The analgesic effects of tryptophan are potentiated by allopurinol (CAS 315-30-0). The analgesic effects shown by tryptophan injection are associated with increased levels of serotonin and 5-hydroxyindoleacetic acid in some areas of the brain. The combined allopurinol and tryptophan treatment elevates the serotonin levels furtherly when they are compared with the values observed in animals receiving tryptophan only. The analgesia caused by tryptophan administration has been attributed to an increased activity of the serotoninergic system involved in the control of pain transmission.

Topics: Allopurinol; Analgesics; Animals; Brain Chemistry; Chromatography, Liquid; Drug Synergism; Hydroxyindoleacetic Acid; Microwaves; Neurotransmitter Agents; Pain; Rats; Rats, Inbred Strains; Sensory Thresholds; Serotonin; Tryptophan

Pyrazinamide (PZA) is increasingly used with isoniazid and rifampicin, in short-course antituberculous chemotherapy in service programme conditions. Complicating arthralgias occur due to hyperuricaemia induced by the inhibition of renal tubular secretion of uric acid by pyrazinoic acid, the main PZA metabolite. Allopurinol (Al), a hypouricaemic agent, provides no substantial clinical improvement. Pharmacokinetics of PZA and its metabolites were studied in six healthy volunteers, in a cross-over design, after a single oral dose of PZA alone and, in a second trial, after the same dose together with Al. Plasma and urinary concentrations were measured by high pressure liquid chromatography with a column of cation exchange resin. Analysis of the pharmacokinetic parameters showed that Al induced marked changes in levels of PZA metabolites and accumulation of pyrazinoic acid. Despite decreasing uric acid synthesis, allopurinol increased plasma concentrations of pyrazinoic acid, which is directly responsible for the inhibition of renal urate secretion. Other drugs, which do not involve xanthine oxidase inhibition, should be used in the treatment of this side effect of chemotherapy.

Topics: Adult; Allopurinol; Drug Interactions; Drug Therapy, Combination; Humans; Joint Diseases; Male; Pain; Pyrazinamide; Tuberculosis, Pulmonary; Uric Acid

Topics: Aged; Allopurinol; Captopril; Drug Synergism; Fever; Humans; Joint Diseases; Male; Muscular Diseases; Pain; Proline

Topics: Africa, Eastern; Animals; Arteriosclerosis; Diet; Finland; Heart Diseases; Humans; Hyperlipidemias; Japan; Milk; Myocardial Infarction; Pain; Plasmalogens; Switzerland; United States; Xanthine Oxidase