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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interactions of caffeine (CAS 58-08-2) with acetylsalicylic acid (CAS 50-78-2, ASA) and paracetamol (CAS 103-90-2) were investigated with regard to the analgesic, antiphlogistic, antipyretic and other properties. The inhibitory effect of paracetamol and ASA on the prostaglandin biosynthesis in a cyclooxygenase preparation from bovine brain in vitro was not affected by the addition of caffeine. Caffeine additively increases the antinociceptive effect of paracetamol with regard to the heat-induced pain in the mouse, as does aminophenazone. The antinociceptive effect of aminophenazone on the mechanically induced pain in the mouse is also additively increased by caffeine. In contrast to the effect of aminophenazone on the inflammatory pain in the rat, the effect of ASA is not increased by caffeine and that of paracetamol only negligibly. The antipyretic effect of paracetamol is additively increased by caffeine in the normothermic rat. The antipyretic effect of ASA and paracetamol on the yeast-induced pyrexia of the rat is not affected by caffeine. Caffeine additively increases the acute antiexudative effect of ASA and aminophenazone on the carageenin-induced oedema of the hind paw of the rat. The increase in locomotor activity caused by caffeine in mouse and rat is neutralised or diminished when the caffeine is given in combination with paracetamol. This effect is maintained even if the rats are pretreated with the combination of active ingredients for 3 weeks. The ulcerogenic effect of ASA in the stomach of the rat is not increased by caffeine. The protective effect of ASA against the hepatotoxic effect of paracetamol in the mouse is not influenced by the addition of caffeine. The plasma levels after the oral administration of 20 mg/caffeine/ kg and 80 mg paracetamol/kg in the rat are not significantly changed when the substances are given in combination. The toxicological advantages resulting from combining ASA and paracetamol with caffeine are discussed.
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PMID:Role of caffeine in combined analgesic drugs from the point of view of experimental pharmacology. 929 78

It has been theorized that adenosine is a leading candidate for the metabolite responsible for ischemic muscle pain. The purpose of this study was to determine the effect of the non-selective adenosine receptor antagonist, caffeine, on ischemic skeletal muscle contraction pain. Seven healthy adult volunteers with no history of pain disorders, systemic disease, or habitual caffeine use, were chosen for the two-session, cross-over, double-blind study. Every subject received either 200 mg of caffeine (NoDoz, Bristol-Myers) or identical placebo 1 hour before each of the two trials. Ischemia of the forearm was achieved by inflation of a blood pressure cuff to 250 mm Hg. Forearm muscle activity was generated by performance of wrist curis using a 5-gram bar at a rate of 40 cycles per minute. Pain was rated at 15-second intervals for 1 minute using a visual analog scale (0 to 10) with verbal descriptors. Significance was determined by univariate and multivariate analyses of variance and covariance including repeated measures. Pain ratings at 15 seconds in the caffeine trial were significantly lower (P < 0.02) than those in the placebo trial. This effect continued at 30 seconds (P < 0.05). However, by 45 seconds, pain in the caffeine trial was not significantly lower (P = 0.4) than that in the placebo trial. These results show that high-dose caffeine exhibits considerable analgesic efficacy in experimental muscle pain, adding support for a role of adenosine in producing ischemic muscle contraction pain.
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PMID:Hypoalgesic effect of caffeine in experimental ischemic muscle contraction pain. 943 87

Pain and discomfort in everyday life are often treated with over-the-counter (OTC) analgesic medications. These drugs are remarkably safe, but serious side effects can occur. Up to 70% of the population in Western countries uses analgesics regularly, primarily for headaches, other specific pains and febrile illness. It is not known whether the patterns of use are consistent with good pain management practices. OTC analgesics are also widely used to treat dysphoric mood states and sleep disturbances, and high levels of OTC analgesic medication use are associated with psychiatric illness, particularly depressive symptoms, and the use of alcohol, nicotine and caffeine. More than 4 g per day of acetylsalicylic acid (ASA) or acetaminophen over long periods is considered abuse. People using excessive amounts of OTC analgesics may need more effective treatments for chronic pain, depression or dysthymia. The possibility that these drugs have subtle reinforcing properties needs to be investigated. Certainly phenacetin, which was taken off the market in the 1970s, had intoxicating effects. A better understanding of patterns of use is needed to determine the extent of problem use of OTC analgesics, and whether health could be improved by educating people about the appropriate use of these drugs.
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PMID:Use and abuse of over-the-counter analgesic agents. 950 57

This study examined the ability of an adenosine kinase inhibitor (5'-amino-5'-deoxyadenosine; NH2dAD), an adenosine deaminase inhibitor (2'-deoxycoformycin), and combinations of these agents to produce a peripheral modulation of the pain signal in the low concentration formalin model. Drugs were administered in combination with 0.5% formalin, or into the contralateral hindpaw to test for systemic effects, and episodes of flinching behaviors determined. Coadministration of NH2dAD 0.1-100 nmol with formalin produced antinociception as revealed by an inhibition of flinching behaviors. This action was peripherally mediated as it was not seen following contralateral administration of the NH2dAD, and was due to accumulation of adenosine and activation of cell surface adenosine receptors as it was blocked by the adenosine receptor antagonist caffeine. Antinociception was intensity-dependent, as it was not seen when higher concentrations of formalin (0.75%, 1.5%) were used. The coadministration of the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine revealed the presence of an inhibitory tone of adenosine when the intrinsic antinociceptive effect of NH2dAD was obscured by the solvent or the stimulus intensity. 2'-Deoxycoformycin 0.1-100 nmol did not produce any intrinsic effect, but 100 nmol coadministered with low concentrations of NH2dAD, which lacked an intrinsic effect, augmented antinociception by NH2dAD. Again, this was a peripheral rather than a systemic response. The combined action of the adenosine kinase and deaminase inhibitors was completely reversed by coadministration of caffeine. Antinociception with NH2dAD is observed at higher concentrations of formalin in second trial experiments. This study demonstrates a peripheral antinociceptive action mediated by endogenous adenosine which accumulates following the peripheral inhibition of adenosine kinase; this action is due to activation of an adenosine A1 receptor.
Pain 1998 Jan
PMID:Peripheral antinociceptive effect of an adenosine kinase inhibitor, with augmentation by an adenosine deaminase inhibitor, in the rat formalin test. 951 63

The present study examined the spinal antinociceptive effects of adenosine analogs and inhibitors of adenosine kinase and adenosine deaminase in the carrageenan-induced thermal hyperalgesia model in the rat. The possible enhancement of the antinociceptive effects of adenosine kinase inhibitors by an adenosine deaminase inhibitor also was investigated. Unilateral hindpaw inflammation was induced by an intraplantar injection of lambda carrageenan (2 mg/100 microl), which consistently produced significant paw swelling and thermal hyperalgesia. Drugs were administered intrathecally, either by acute percutaneous lumbar puncture (individual agents and combinations) or via an intrathecal catheter surgically implanted 7-10 days prior to drug testing (antagonist experiments). N6-cyclohexyladenosine (CHA; adenosine A1 receptor agonist; 0.01-1 nmol), 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenos ine (CGS21680; adenosine A2A receptor agonist; 0.1-10 nmol), 5'-amino-5'-deoxyadenosine (NH2dAdo; adenosine kinase inhibitor: 10-300 nmol), and 5-iodotubercidin (ITU; adenosine kinase inhibitor; 0.1-100 nmol) produced, to varying extents, dose-dependent antinociception. No analgesia was seen following injection of 2'-deoxycoformycin (dCF; an adenosine deaminase inhibitor; 100-300 nmol). Reversal of drug effects by caffeine (non-selective adenosine A1/A2 receptor antagonist; 515 nmol) confirmed the involvement of the adenosine receptor, while antagonism by 8-cyclopentyl-1,3-dimethylxanthine (CPT; adenosine A1 receptor antagonist; 242 nmol), but not 3,7-dimethyl-1-propargylxanthine (DMPX; adenosine A2A receptor antagonist; 242 nmol), evidenced an adenosine A1 receptor mediated spinal antinociception by NH2dAdo. dCF (100 nmol), which was inactive by itself, enhanced the effects of 10 nmol and 30 nmol NH2dAdo. Enhancement of the antinociceptive effect of ITU by dCF was less pronounced. None of the antinociceptive drug regimens had any effect on paw swelling. These results demonstrate that both directly and indirectly acting adenosine agents, when administered spinally, produce antinociception through activation of spinal adenosine A1 receptors in an inflammatory model of thermal hyperalgesia. The spinal antinociceptive effects of selected adenosine kinase inhibitors can be significantly augmented when administered simultaneously with an adenosine deaminase inhibitor.
Pain 1998 Feb
PMID:Antinociception by adenosine analogs and inhibitors of adenosine metabolism in an inflammatory thermal hyperalgesia model in the rat. 952 Feb 38

A 36-year-old woman presented to the emergency department with right hip pain of one week's duration. An x-ray of the hip was unremarkable. She was diagnosed with trochanteric bursitis, given ibuprofen (800 mg tid) and crutches, and sent home. The next day, continual pain and progressive functional impairment prompted her to see an orthopedist. He concurred with the initial diagnosis and administered a corticosteroid injection into the right trochanteric bursa. Propoxyphene (65 mg q4h prn) was added to her medical regimen, and she was again sent home. Pain developed in the right sacroiliac area the next day. Within 24 hours, the right shoulder and right sternoclavicular joint were also involved, and the patient began having subjective fever and chilliness. She returned to the orthopedist and was immediately referred to a rheumatologist who ordered blood cultures and admitted her to the hospital.
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PMID:Arthralgias following dilation and curettage. 960 51

Adenosine and ATP exert multiple influences on pain transmission at peripheral and spinal sites. At peripheral nerve terminals in rodents, adenosine A1 receptor activation produces antinociception by decreasing, while adenosine A1 receptor activation produces pronociceptive or pain enhancing properties by increasing, cyclic AMP levels in the sensory nerve terminal. Adenosine A3 receptor activation produces pain behaviours due to the release of histamine and 5-hydroxytryptamine from mast cells and subsequent actions on the sensory nerve terminal. In humans, the peripheral administration of adenosine produces pain responses resembling that generated under ischemic conditions and the local release of adenosine may contribute to ischemic pain. In the spinal cord, adenosine A receptor activation produces antinociceptive properties in acute nociceptive, inflammatory and neuropathic pain tests. This is seen at doses lower than those which produce motor effects. Antinociception results from the inhibition of intrinsic neurons by an increase in K+ conductance and presynaptic inhibition of sensory nerve terminals to inhibit the release of substance P and perhaps glutamate. There are observations suggesting some involvement of spinal adenosine A2 receptors in pain processing, but no data on any adenosine A3 receptor involvement. Endogenous adenosine systems contribute to antinociceptive properties of caffeine, opioids, noradrenaline, 5-hydroxytryptamine, tricyclic antidepressants and transcutaneous electrical nerve stimulation. Purinergic systems exhibit a significant potential for development as therapeutic agents. An understanding of the contribution of adenosine to pain processing is important for understanding how caffeine produces adjuvant analgesic properties in some situations, but might interfere with the optimal benefit to be derived from others.
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PMID:Adenosine receptor activation and nociception. 965 Aug 42

Clinical studies of topical therapy against Herpes simplex virus (HSV) infections have been reviewed. Idoxuridine (IDU) 15% in dimethyl sulfoxide (DMSO), interferons, and penciclovir result in significant clinical benefit against this virus. IDU reduced pain duration and decreased time to loss of crust in a study of 301 patients. Alpha-interferon has shown synergism with other anti-HSV drugs such as caffeine, trifluorothymidine (TFT), DMSO, and nonoxynol-9. Finally, in a study of over 2,000 patients, application of penciclovir cream, both early and late in the course of HSV infection, decreased the duration of lesions, pain, and viral shedding. Acyclovir (ACV)-resistant strains of HSV are susceptible to (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and ascorbic acid shows promising effects against HSV. Using a vehicle that enhances skin penetration of a drug or possibly further exploring combination therapy may result in efficacious treatment of HSV. The possibility of topical vaccination or topical gene therapy may also prove beneficial in the future.
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PMID:Treatment of Herpes simplex virus infections with topical antiviral agents. 968 81

The delivery ability of a pressure-controlled colon delivery capsule (PCDC) containing caffeine as a test drug was evaluated after oral administration to healthy male human volunteers. The driving force causing PCDC disintegration in the intestinal tract is the physiological luminal pressure which results from peristalsis. Three kinds of PCDCs having different thickness of a water-insoluble polymer membrane was prepared by coating the inner surface of the gelatin capsules with ethylcellulose (EC). The mean thickness were 40 +/- 1 (SE) for type 1, 44 +/- 1 for type 2 and 50 +/- 1 micron for type 3 PCDC, respectively. Caffeine was dissolved with a suppository base (PEGs 400 and 1000) and the capsules were filled. Doses were 15, 45 or 75 mg. After blank saliva samples were obtained, test preparations were orally administered to the volunteers and saliva samples were collected for 1 min intervals hourly from 1 to 10 h in the fasted state study, and from 1 to 20 h and at 25 h in the fed state study. Caffeine concentrations in the saliva samples were analyzed by HPLC. The maximum salivary caffeine excretion rate increased as the oral caffeine dose increased. The maximum salivary caffeine excretion rate increased predominantly compared to the pre-dose level in 75 mg dose study. Therefore, all following studies were performed with this dose. The first appearance time of caffeine into the saliva, TI, was used as a parameter to estimate the disintegration time of test preparations in the gastrointestinal tract. The mean TI of types 1, 2, and 3 PCDCs were 3.0 +/- 0.4, 4.0 +/- 0.4 and 4.5 +/- 0.3 h, respectively. After oral administration of 75 mg caffeine in pain gelatin capsule as a reference preparation, caffeine appeared in the saliva within 0.5 h. The mean hardness of the PCDCs were 1.05 +/- 0.10 (type 1), 1.55 +/- 0.06 (type 2) and 2.08 +/- 0.15 newton (type 3), respectively. There were good correlations between three parameters: EC coating membrane thickness, hardness and TI (determination coefficient r2 = 0.935 between TI and thickness, r2 = 0.998 between thickness and hardness, r2 = 0.958 between hardness and TI). The effect of food intake on the delivery ability was examined with type 3 PCDCs. Food intake prolonged the mean TI, from 4.5 +/- 0.3 to 7.8 +/- 1.3 h. This increase is thought to be ascribed to prolonged gastric emptying time. Comparison with reported colon arrival times indicates that the type 3 PCDC functions in colon delivery of caffeine and is thought to be applicable to other drugs.
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PMID:Evaluation of intestinal pressure-controlled colon delivery capsule containing caffeine as a model drug in human volunteers. 968 42

Chronic pain affects 75 million US citizens. A number of pharmacologic treatments are available for chronic pain that does not respond adequately to nonpharmacologic methods. Long the mainstay of chronic pain management, nonsteroidal anti-inflammatory drugs (NSAIDs) are known to be associated with gastrointestinal (GI) and renal toxicities, a particular problem for the elderly population, which commonly experiences chronic pain, such as that associated with osteoarthritis (OA). Several non-NSAID, non-narcotic therapies are available for noninflammatory pain. Acetaminophen is as effective as NSAIDs for the management of mild-to-moderate OA pain and is the recommended first-line therapy by the American College of Rheumatology (ACR). Propoxyphene, widely believed to be safe and effective, may, in fact, be no more effective-and perhaps less effective-than acetaminophen or ibuprofen. A relatively new analgesic, tramadol, appears to be a useful therapy for patients who do not receive adequate pain relief with acetaminophen and are at risk for NSAID-related side effects. For localized chronic pain associated with OA, topical capsaicin is also an effective analgesic.
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PMID:Non-NSAID pharmacologic treatment options for the management of chronic pain. 971 34


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